Ajman University of Science & Technology Faculty Of Pharmacy & Health Sciences

.………………….

TRAINING MANUAL FORPHARMACEUTICAL TECHNOLOGY

Central Committee

Department of Pharmaceutics

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2000 - 2001

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From The President

In The Name of Allah, Most Merciful, Most Compassionate, And Peace be Upon Mohammed.

Dear Students,

The Strategic vision of Ajman University of Science and Technology as an Open System where the environment of a conventional university overlaps with the employment market is committed to train and educate the pharmacy practitioners of tomorrow, in spite of all difficulties that we might face.

The University was able to overcome many difficulties by adhering to our strategic vision that is based on accurate and clear-cut work plan. The implementation of Euro–Arab Research Network on July 24, 2000 have set the infrastructure of the Innovative Medical Environment needed for pharmacy practice and clinical training of current B. pharmacy programme. In addition, the university made agreements with nine hospitals in different Emirates supplement the clinical facilities provided. These agreements shall give our students the chance to interact with enough practitioners and preceptors needed for our programme during study course.

The university has been guided by a well-established vision that is based on precise curricula related to a tangible real world. This vision can only bear its fruit creatively through consistent continuing work to have automatic interaction with higher education systems by breaking the barrier between the university and the employment market.

I am pleased to introduce to you, the Faculty of Pharmacy and Health Sciences “TRAINING MANUAL

FOR PHARMACEUTICAL TECHNOLOGY”. Through this training process in all branches of the university, students will complement their academic knowledge with pharmaceutical technology training concept.

Assalam alaikum

Dr. Saeed Salman President of Ajman University of Science and Technologyand President of Arab Private Institutions for Higher Education.

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TABLE OF CONTENTS

Section 1 From the President (H.E. Dr. Saeed Salman)Section 2 Objective of the training programe 6

pre-requisites description justification objectives student activity report Student Evaluation Distribution of the evaluation marks Evaluation Marks Sheet Alternatives for special students

Section 3Review of Pharmaceutical Calculation Used In Extemporaneous Preparations.

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Section 4 Pre-formulation training in pharmacy laboratory

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Solution 21Strong Sodium Salicylate mixture BPCPreparation of peppermint water B.PSolutions For Internal use

Solutions For Internal use

Solutions For External use:Aqueous Iodine Solution Preparation of Lysol

Section 5 Syrups 25Preparation of Syrup B.P

Acacia Syrup USPCough SyrupCough Syrup for diabeticAromatic Elixir USP

Section 6 Ear drops 28Sodium Bicarbonate ear drops B.PStarch Glycerol ear drops

Section 7 Emulsions 291- Emulsion For Internal use :Acacia Emulsion

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2-Emulsions for External use :White Liniment B.PCalamine Lotion B.P

Section 8 Cosmetic preparation 321- Cosmetic Creams : Vanishing Cream B.P Acid conditioning Creams Cold Cream Cleansing cream 2- Shampoos : Shampoo Paste or Creams

Dandruff ShampooHair Conditioners3- Make –Up Preparations : LipsticksEye Make-up Preparation of Deodorant Stick

Section 9 Powders 401- Properties of powders :2- Classification of powders: Preparation of divided powder

Preparation of dusting powder

Section 10 Granules 461-Preparation of some granulating agents and

preparation of simple granulation by wet method. 2-Preparation of Effervescent Granulation :Preparation of sodium citra tartarate ( B.P.C.)

Section 11 Tablets 511- Tablet Exciepients2- Single Punch Tablet Machines3-Tablets Preparation MethodsPreparation of Asprin Tablet by Direct Compression Preparation of Asprin Tablet byDry Granulation Method Preparation of Chewable Antacid Tablet by Wet Granulation Method4- Evaluation of Tablets

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Unofficial TestsOfficial Standards

Section 12 Capsules 651- Hard Gelatin Capsules2- Methods od Preparation of CapsulesPreparation OF Ephedrin Sulfate and Phenobarbital Capsules

Section 13 Suppositories 701- Method of Preparation2- Suppository Bases3- Calibration of Molds4- Standardization of SuppositoriesPreparation of Glycerogelatin Bases

Section 14 APPENDIX (A) Latin Terms and Common Abbreviations APPENDIX (B) General “Good Compounding Practice “ for Non-sterile Products

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700415 Pharmaceutical Technology Training (0+3):

Pre-requisite: successful completion of the six Levels (i.e 100 Cr. Hr.) and 700413Supervision: Faculty member Assessment: A-F grade DESCRIPTION: The purpose of this training is to introduce the student to the

pharmacist’s role in the industrial setting. Students are expected to spend 120 contact hours in a pharmaceutical company under the supervision of a faculty member and represantitive members of the company. Training should be rotated in the different production lines, quality control, quality assurance, raw material handling and marketing departments.

JUSTIFICATION: To train students in all departments of the factory, to be aware of all steps that ensure high quality production. In addition, students should learn how to discover defects of the products if any, so that quality of marketed products will be ensured. Students shall spend 120 hrs (15 working days) at the different departments divided as follows:

1 Two days at Warehouse (Raw material handling Department) to learn the specification, testing, handling and storage requirements of raw material and packing.

2 Seven days in the drug Production Department of different dosage forms to learn all production stages such as preparation of raw material that will be used in drug formulation, calculation needed for accurate formulation, steps of manufacturing and handling of machinery and products. In case of preparation of sterile products, students should learn the proper environments and conditions required for production

3 Six days Quality Control, Quality Assurance and marketing:

Students shall spend three days in Quality Control

where they get exposed to methods used to test the raw

materials, packing materials, semi-manufactured

materials and final production. These tests could be

chemical, physical or biological. The trainee should be

exposed to different analytical equipments and official

FDA and USA requirements.

Students shall spend two days in Quality Assurance where they learn from inspectors and assurance officers how to fill forms to check that all processes in the industry have been carried according the specified instructions.

Students shall spend one day in marketing department to learn steps and methods used to promote drug products, techniques involved to ensure the stability of these products and bookkeeping of soled products.

4 Assessment forms that should be signed are form 7, student, site and academic adviser’s reports

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Activity:

The student will submit a report on all the training areas i.e. pre-formulation, production, quality control, quality assurance, packaging and marketing.

Student Evaluation

Student should submit the activity report of the pharmaceutical technology training, student report on the training and site advisor report to the central

training committee or to its representative in Ajman, Abu-Dhabi, and Al-Ain.(Forms are enclosed in section 11)

Distribution of the evaluation marks :

Attendance 10%Adherence to professional attitude 10%Activity report 30%Evaluation of the central committee on the form 7 30%(see form 7 , section 11 )Site advisor evaluation 20%

Total Marks 100

Refer to the evaluation marks sheet in section 11

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FORM 7

Ajman University of Science and TechnologyFaculty of Pharmacy and Health Sciences

Training committee

Acceptance of the PharmacyStudent training through the Pharmaceutical Technological Training

Course No. 700415

Progress report: to be submitted at the end of the Pharmaceutical Technology Training

Student Name :

ID # :

Pharmaceutical Factory name :

Academic Advisor name :

Pharmaceutical Factory Advisor name :

Starting date of the training :

End date of the training :

Student Evaluation Work During The Training Period

How would you rate the student with respect to his/her pharmaceutical technology training knowledge?

Student's Performances:

1- Research and Development

Excellent Very Good Good Average Poor

2- In process control and manufacturing oral solid

Excellent Very Good Good Average Poor

3- In process control and manufacturing oral liquids

Excellent Very Good Good Average Poor

4- Dispensing and warehousing

Excellent Very Good Good Average Poor

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PHARMACEUTICAL TECHNOLOGY TRAINING

(700415)

Evaluation Marks Sheet

Student’s Name :-----------------------

Students ID :-------------------------

NO.

Attendance

(10%)

Professional Attitude

(10%)

Activity Report

(30%)

Preparations

&Evaluation

(50%)

Total

(100%)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

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Alternatives for special students

In accordance with the provision given by H.E. Dr. Saeed A. Salman, The President of the University to students that wants to be trained in the summer in a pharmaceutical company at their country or to female students that they wish to be trained in Faculty of Pharmacy Laboratories; the central committee adopted the following: 1. Students wants to be trained in the summer in a pharmaceutical company at their country have to get the approval, in writing, that the company will follow the requirement of our training and has to appoint supervisor for his training. The central committee will then sent its recommendation to the Dean. The Dean’s acceptance letter will be forwarded to the company. After the completion of training, all reports should be submitted to the central committee. The central committee appoints a subcommittee to evaluate the student following the same rules to ensure uniformity of training.

2. In Site Training :Students that they wish to be trained in Faculty of Pharmacy Laboratories shall take tutorial interactive lectures using multimedia, video and assigned seminar to cover quality assurance, quality control and marketing. The faculty supervisor shall evaluate the students (30%) including a written Examination. In addition, students shall prepare the formulations listed in this manual (Sections 4-12) and pas an examination according the evaluation mark sheet.

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Section (3)

Review of Pharmaceutical Calculation Used In Experaneous Preparations.

Introduction:

Prescription compounding is a rapidly growing component of pharmacy practice. This can be attributed to a number of factors, including individualized patient therapy, lack of commercially available products, home healthcare, intravenous admixture programs, total parenteral nutrition programs and "problem solving" for the physician and patient in enhancing compliance with a specific therapeutic regimen. Pharmacists are creative and should have the ability to formulate patient-specific preparations for providing pharmaceutical care. Most compounded prescriptions require a number of calculations as part of preparation, packaging and dispensing.

Potential for Error:

One of the greatest potentials for error in prescription compounding is in the area of pharmacy math, or pharmacy calculations. Even though most of the processes are relatively simple, a misplaced decimal or "estimated" value for a medication can have serious consequences, including death. There is no excuse for ignorance in this area and, an individual unprepared to do the necessary calculations should not be involved in pharmaceutical compounding. It is of utmost importance that pharmacists be extremely well-grounded in the practice of pharmaceutical calculations as there is "zero-tolerance" allowed in these vital operations.This issue of Secundum Artem is provided as a review and reference source for commonly performed compounding calculations.

Solubility Expressions :

Solubility expressions in the literature and in the United States Pharmacopeia (USP) are "x:y" and "x in y", such as 1:4 and 1 in 4. This is stated as one part of solute plus 4 parts of solvent. This results in a 1:5 solution, or 1 part of solute in 5 parts of solution. A solubility expression is different than a ratio expression as just described. Let's look at it again. A solubility of 1:3 is l g solute + 3 mL solvent. This results in a 1:4 solution (1 part of solute in 4 parts of solution), a 1:3 solution is l g in 3 mL solution (sufficient solvent to make).

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Least Measurable Quantities (Volume/Weight):

A pharmacy has a torsion balance with a 5 mg sensitivity. What is the smallest quantity that can be accurately weighed with a maximum of 5% error?

(5 mg x 100) / 5% error = 100 mg

Their electronic balance has a sensitivity reading of 0.1 mg. What is the smallest quantity that can be reasonably weighed?A digital balance does not change its readout until the largest unit of material is placed on the balance pan. If the readability of a balance is 0.1 mg, the change in the digit on the right does not occur until 0.1 mg is added. In other words, 0.04 mg will not result in a digit change. If one tries to weigh 0.1 mg, one might actually place 0.14 mg of drug on the pan but the readout will only be 0.1. Therefore, use the same general principal as with torsion balances and weigh not less than 20 times the readability (2 mg) of the balance.

Calibration of Droppers:

An anticholinergic liquid has been presented for a toddler at a dose of 0.25 mL. The dropper dispensed with the medication delivers 56 drops of the liquid per 2 mL. How many drops shall the parents be instructed to give the toddler?

56/2 = 28 drops/mL0.25/1 = x/28 , x = 7 drops

Reducing/Enlarging Formulas:

A formula for 100 mL of an Ibuprofen gel requires 2 g of Ibuprofen powder. What quantity of the gel would be required for 240 mL of the product?

2 /100 = X240 , X = 4.8 g

Partial dosage units:

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Rx Indomethacin 5 mg/5 mLOra Plus 60 mLOra Sweet qs 120 mL

How would you obtain the quantity of indomethacin required for this Rx using indomethacin 25 mg capsules?5 mg/5 mL = 1 mg/mL1 mg/mL x 120 mL = 120 mg needed120 mg/25 mg/capsule = 4.8 capsules requiredEmpty the contents of 5 capsules onto a tared weighing paper and weigh (Ex: 1.6 g).The contents weigh 1.6 g. You need to remove: 4.8/5 = 0.96 x 1.6 g = 1.536 g of the mixture for the prescription.

Stock Solutions:

A pharmacist is preparing an ophthalmic decongestant solution in batch form. Each of three bottles will contain 15 mL. The preservative to be incorporated is 0.01% benzalkonium chloride (BAK). The pharmacist has a stock solution containing 17% BAK. How much of this stock solution would be required for the three bottles?15 x 3 = 45 mL45 x .0001 = .0045 g0045/ x =17/100x = 0.026mL

Specific Gravity in Weighing/Measuring:A pharmacist receives a prescription for 120 mL of a 3% w/v Hydrochloric Acid solution. The density of concentrated hydrochloric acid (37%) is 1.18 g/mL. How many milliliters of the concentrated acid would be required for the Rx?3% = .03.03 x 120 mL = 3.6 g required Volume =3.6 g/1.18 g/mL= 3.05 mL

37% = 0.37 , 3.05 mL /0.37= 8.24 mL

Mixing Products of Different Strengths:

A pharmacist receives an order for 120 g of a 0.1% corticosteroid ointment. On hand are 1 oz of 0.1%, 2 oz of 0.15% and 2 ½ oz of 0.005%, all in the

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same ointment base. If these three ointments are mixed together, how much additional corticosteroid powder should be added to prepare the prescription? Assume the quantity of corticosteroid added will be negligible compared to the 120 g total weight.120 x .001 = 120 mg needed

30 x 0.001 = 30 mg

15 x .0015 = 22.5 mg

75 x .00005 = 3.8 mg------

Total 56.3 mg

120 mg - 56.3 mg = 63.7 mgIn what quantities could a 50% dextrose in water be mixed with a 5% dextrose in water to obtain 900 mL of 15% dextrose in water?50 10 ÷ 5 = 2 155 35 ÷ 5 = 7

-------Total: 9 parts

(2/9)x 900 = 200 mL of D50W

(7/9)x 900 = 700 mL of D5W-------------900 mL Total Volume

Powders for Reconstitution:

The directions to constitute an amoxicillin suspension 250 mg/5 mL, 150 mL, state that 111 mL of Purified Water are required. The physician has requested the product be constituted at a concentration of 500 mg/5mL. How much Purified Water would be required?150 mL - 111 mL = 39 mL occupied by powder

250 mg/5 mL = 50 mg/mL

50 mg/mL x 150 mL = 7.5 g of powder

7.5/0.5 = 15 doses

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15 doses x 5 mL = 75 mL volume

75 mL - 39 mL = 36 mL required

MilliEquivalents:

A prescription calls for 25 milliequivalents of sodium chloride. What quantity, in mg, would be required? 1 equivalent NaCl = 58.5 gm, 1 milliequivalent = 58.5 mg; 25 mEq x 58.5 mg/mEq = 1.463 gA pharmacist receives an order for 10 mEq of Ca+. How much of a standard 10% CaCl2 solution should be used for this order?Ca = 40/2 = 20 mg/mEq

1/10 mEq = 20 mg/ x , x = 200 mg Ca required

CaCl2 = 40 + 71 = 111

40/111 =200/ x mg , x = 555 mg CaCl2 required

10 /100ml = 0.555 g / x , x = 5.55 mL of the 10% CaCl2 solution

Millimoles:

How many millimoles of NaCl are contained in 1 liter of 0.9% Sodium Chloride Solution? (Formula weights: Na=23, Cl=35.5, NaCl=58.5).0.009 x 1000 mL = 9 g NaCl

1 mole NaCl weighs 58.5 g

1/58.5g = x /9g , x = 0.154 mole = 154 millimoles

Osmolality:

What is the osmolality (number of milliosmoles) of 1 liter of 0.9% sodium chloride solution? (Assume complete dissociation)Na=23, Cl=35.5, NaCl=58.5, NaCl --> Na+ + Cl

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# millimoles NaCl present per liter = 154 from previous problem

154 millimoles NaCl x 2 species (Na + Cl) = 308 mOsmol/literWhat is the osmolality of 10% CaCl2 solution? (Assume complete dissociation) (Formula weights: Ca=40, Cl=35.5, CaCl2=111g/L)10% CaCl2 = 100 g/1000 mL

100 / 111 g = x / 1 molex = 0.9 moles/liter = 900 millimoles

CaCl2 ----> Ca++ + 2 Cl = 3 species

900 millimoles CaCl2/L x 3 species = 2700 mOsmol/Liter

Units to Weight Conversions:

A Rx order calls for 150,000 units of nystatin per gram of ointment with 60 grams to be dispensed. How much nystatin would be weighed? (4400 USP Nystatin units/mg)150,000 u/g x 60 g = 9,000,000 units needed

9,000,000/4400 u/mg = 2.045 g required

Shelf Life Estimates:

Shelf life estimates can be made using the equation: t90 Orig

t90New = -------- 3∆T/10

where ∆T = change in temperature3 is a reasonable estimate for the "Q" value, based on energies of activation from the Arrhenius equation.An antibiotic solution has a shelf-life of 96 hours when in a refrigerator. If it is necessary that a patient use it in an ambulatory pump at approximate body temperature (30oC) over 6 hours, would it still retain at least 90% of its original potency during the entire period of administration?

t90 =96 /325/10

= 6.16 hoursAns. = yes

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A prescription is received for an ophthalmic solution with a shelf-life of 4 hours at room temperature. The preparation is to be administered in a physicians office at 12:00 noon the next day. Can it be prepared the evening before at about 8:00 pm and still retain at least 90% of its shelf life if stored in a refrigerator?

t90 = 4 / 3-20/10 = 4 / 3-2 = 36 hours Ans. Yes

A reconstituted antibiotic has a shelf-life at room temperature of 3 days. How long would the preparation be good if stored in a refrigerator? (A reasonable estimate based on (t90).

t90 = 3d / 3 2 = 3 X 9 = 27 days

Ophthalmic and Nasal Solutions-Sodium Chloride Equivalents:

How much sodium chloride is required to render the following Rx isotonic? Rx Lidocaine HCl 1% (NaCl equiv. = 0.22)

Cocaine HCl 1% (NaCl equiv. = 0.16)Epinephrine Bitartrate 0.1% (NaCl equiv. = 0.18)Sterile Water qs 50 mLSodium Chloride qs

50 x .01 = 0.5 x .22 = 0.110

50 x .01 = 0.5 x .16 = 0.080

50 x .001 = .05 x .18 = 0.009-----0.199 g

The ingredients represent the equivalent of 0.199 g of NaCl.

50 x .009 = 0.45 g NaCl to make 50 mL water isotonic

0.45 - 0.199 = 0.251 g NaCl needed to add to this Rx to make it isotonic

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Ophthalmic and Nasal Solutions-Buffer Solutions & pH:

Rx Optimycin 1%NaCl qsPhosphate Buffer pH 6.5 qs 100 mL

Sorensen Modified Phosphate Buffer Acid Stock Solution (1/15 M) Alkaline Stock Solution (1/15 M)Sodium Biphosphate, Anhy. 8.006 g Sodium Phosphate, Anhy. 9.473 gPurified Water qs 1000 Purified Water qs 1000 mL

mL of 1/15 M Sodium mL of 1/15 M SodiumpH Biphosphate Solution Phosphate Solution

5.9 90 106.2 80 206.5 70 306.6 60 406.8 50 507.0 40 607.2 30 707.4 20 807.7 10 908.0 5 95To prepare 100 mL of pH 6.5 phosphate buffer solution, use 70 mL of 1/15 Molar Solution Biphosphate Solution and 30 mL of 1/15 Molar Sodium Phosphate Solution.

Nasal Solutions-Calibrating a Dropper/Sprayer:

A nasally administered product has a dose of 25 µg. A 0.5% solution is prepared and placed in a nasal spray bottle. Ten "squeezes" into a plastic bag by the patient weighed 500 mg. How many squeezes are required to administer the 25 Fg dose? (assume weight of solution is 1 gram per mL, i.e., 500 mg = 0.5 mL).0.5% = 0.5 g/100 mL

0.5 g x g ------ = ----- x = .0025 g/0.5 mL or 2.5 mg/0.5 mL (2,500 µ/0.5 mL)100 mL 0.5 mL

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Since 10 squeezes expels 2,500 µg, there would be 250 µg in 1 squeeze.

Capsule Filling-Powder Displacement:

A pharmacist receives a prescription for forty-eight 15 mg piroxicam capsules. A #1 capsule filled with piroxicam weighs 245 mg tare weight; a capsule filled with lactose weighs 180 mg tare weight. How much piroxicam and lactose are required for the prescription? Prepare sufficient powder for 50 capsules (2 extra).50 X 15 = 750 mg piroxicam

15 / 245 = x / 180x = 11 mg15 mg piroxicam occupies a similar volume as does 11 mg lactose

180 mg - 11 mg = 169 mg lactose/capsule169 x 50 = 8.45 g lactose required

Suppositories/Troches/Lozenges-Displacement Factors:

Rx Zinc Oxide 300 mgCocoa Butter qs

If the density factor for cocoa butter is 0.9 and for zinc oxide is 4.0, and the suppository mold holds 2.0 g of cocoa butter, how much cocoa butter would be required to prepare 12 of the suppositories for this prescription?Solution:Total weight if just cocoa butter was used:

12 x 2.0 g = 24 g

The density ratio is:

4/0.9 = 4.44

The weight of zinc oxide required is 3.6 g

The amount of suppository base displaced by the active drug is:

3.6 g/4.44 = 0.81 g

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The weight of the suppository base for the prescription is:

24 g - 0.81 g = 23.19 g

Emulsions-Nucleus:

Rx Mineral Oil 30%AcaciaFlavor, QSPurified Water, QS 120 mL

Using a 4:2:1, Continental Method, how much Acacia is required for this Rx?30% x 120 mL = 36 mL

Oil:Water:Acacia = 4:2:1

36 /4 = x/1 , x = 9 grams of Acacia required.

Pre-formulation training in pharmacy laboratory

All these Preparations Should Be Done By Students.Section (4)

SOLUTIONS

Strong Sodium Salicylate mixture BPC

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RxSodium Salicylate 10gSod.metabisulphate 1gDouble strength chloroform water 525mlWater ad 1000ml

Send 50ml

Note:Double strength chloroform water :

RxChloroform 5mlPurified water ad 1000ml

Note:i-make your calculation and be sure it will be as follows

RxSodium Salicylate 0.5gSod.metabisulphate 0.05Double strength chloroform water 26.25ml

Water ad 50ml

ii-That the limitation of prescript balance is 120g X 120gSo you should use Alginate method to accurately deliver Sod.metabisulphate(0.05g/50ml) preparation ) (i.e dissolve 0.2g of Sod.metabisulphate in 4mlof distilled water & use one ml iii-Role of ingredients & use should be known.

Preparation of peppermint water B.P

RxPeppermint 2mlTalc 15gPurified water ad 1000ml

Sent 100mlProcedure:

1-Weigh 1.5g of talc and put it into a mortar2-add 0.2 ml of peppermint & levigate to adsorb the oil onto the finely talcpowder to ensure dispersion .3-add water to the mortar & mix will

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4- transfer to the bottle and add the remaining water & shake it for 10 min.5- filter & place it in dispersing bottle & adjust volume.Use as carminative & flavor agent

Solutions For Internal use

RxPotassium iodide 25gIodine 12.5gAlcohol 90% 40mlWater 25mlPeppermint oil 4mlGlycerol…upto 1000ml

Sent to 40ml

Label: Use as directed.

Method:

Dissolve required amount of Potassium iodide in Water in a conical flask. Then add Iodine to the above solution.(Although Iodine is slightly soluble in Water put it is readily soluble in aqueoussolution of Iodine)Dissolve Peppermint oil in Alcohol 90% and then add to Iodine mixture and mix well. Make up to volume with Glycerol and mix thoroughly. Transfer in to a wide mouth bottle, label and dispense.

Role of Ingredients:

Potassium iodide : Expectorant and to increase the solubility of IodineIodine : ExpectorantAlcohol 90% : Solvent of Peppermint oilWater : Solvent of Potassium iodide and IodinePeppermint oil : Flavoring agentGlycerol : Humectants, Emollient and vehicle

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Use: Expectorant

Storage : Store in cool placeDirection : Shake well before use, not to be swallowed in

a large amount.

Solutions For External use:Aqueous Iodine Solution

RxIodine 50gPotassium iodide 100gWater up to 1000ml

Sent 100ml

Method:Potassium iodide and Iodine are dissolved in small portion of purifiedWater by stirring & shaking till dissolve completely.sufficient Water is added to make the required volume

Use: disinfectant

Preparation of Lysol

Rxm-Cresol 500mlVegetable oil (lin seed oil) 180mlPotassium Hydroxide 42gpurified Water ad 1000ml

Sent 50ml

Method:Weigh Potassium Hydroxide & dissolve it in small portion of Water andadd 18ml of lin seed oil. Heat in Water path with constant stirring. After

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saponificat add m-Cresol with constant agitation till clean solution results.Complete the volume to 1000ml with water.

Use : External disinfectant

Section (5) SYRUPS :

Preparation of Syrup B.P

RxSucrose 667gPurified Water Q.S 1000g

Sent 300ml

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Procedure: Dissolve the Sucrose in Purified Water in beaker by careful heating onWater path. Stir frequently until dissolved & adjust volume. Cool it andfilter through gawz.

Note: it is preferred to add 10% Glycerol to act as preservative & to preventcrystallization.

Acacia Syrup USP

RxAcacia 1gSod. Benzoate 0.01gVanilla Tincture 0.05mlSucrose 8gPurified Water Q.S 100ml

Procedure:1. Mix Acacia, Sod. Benzoate & Sucrose.2. Add small portion of Purified Water and mix well.3. Heat the mixture on a water path until solution is completed.4. When cool, add the Vanilla Tincture & complete with water to

100ml

Cough Syrup

RxDiphenyl hydramine Hcl gr.v V 5*0.065=0.325g Ammonium chloride gr VL 45*0.065=2.925gSod. Citrate gr XX 0.065*20=1.300gAqueous (H2O) flz ii 4*2=8mlFlavor & Colour Q.S.Syrup Q.S.

Procedure:- Dissolve in 8ml of H2O (in a beaker) - Transfer the solution to a measure cylinder(100ml).

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- Complete with syrup to 100ml.- Transfer the preparation to glass bottle, add flavor & colour (1 drop of rose oil & 2drops of colour)

Role of each Ingredienti. Diphenyl hydramine Hcl : antihistamineii. Ammonium chloride : Expectorantiii. Sod. Citrate : Expectorantiv. Syrup : Vehicle, solvent & Sweeting agentv. Water : Solvent

Use:For cough

Cough Syrup for diabetic

RxDiphenyl hydramine Hcl gr.v V 0.325G Ammonium chloride gr VL 2.9859Sod. Citrate gr XX 1.3gAqueous (H2O) flz ii 4*2=8mlSaccharine Sod. 0.084gMethyl cellulose (0.5%w/v) Q.S.Flavor & Colour Q.S.

Sig: one table spoon to be taken

Procedure:As in cough syrup (except the prepared of Methyl cellulose(0.5%w/v)

Use:cough syrup for diabetic

N:B prepared of Methyl cellulose (0.5%w/v)i. Put 50ml boiling water in beaker &

Aromatic Elixir USP

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RxRose Oil 0.6mlPeppermint oil 0.6mlSyrup 375mlTalc 30gAlcohol 30gpurified Water Q.S 1000ml

Sent 100ml

Calculation: factor use = 100/1000 = 0.1

RxRose Oil 0.0mlPeppermint oil 0.0mlSyrup 37.5mlTalc 3.0gAlcohol 25mlpurified Water Q.S 100m

Procedure:

1. Put Rose Oil, Peppermint oil, Talc and Alcohol in a dispensing bottle and shake very well.

2. Add 20ml of purified Water and shake well3. filter using buchner funnel.4. transfer the filtrated into a measuring cylinder and all syrup &

complete volume to 100ml by purified Water5. Write label.

Section (6)EAR DROPS

Sodium Bicarbonate ear drops B.P

RxSodium Bicarbonate 5gGlycerol 30mlDistilled water ad 100ml

Sent 50ml

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Calculation : factor = 0.5

Procedure:1) Dissolve Sodium Bicarbonate in a portion of water & shake well2) Add 15ml of Glycerol & shake & complete volume with water to

50ml3) Write label

Starch Glycerol ear drops

Rx after cal.Starch (soluble) 100g 5gGlycerin 700ml 32mlWater ad 1000ml 50ml(i.e 10ml)

Sent 50ml

Calculation : factor = 50/100 = 0.05

Procedure:1. Dissolve 5g of starch in 7ml of water2. Add 35ml of glycerin and shake well3. adjust volume to 50ml with water4. Write label.

Section (7)EMULSIONS

In pharmacy it is generally accepted that the term ‘emulsion’ as a dosage form refers only to products for oral adminstration.Emulsion for oral use are almost invariably o/w and are a convenient means of administering oils and fats or oily solution of unstable drug of low aqueous solulibilty

1- Emulsion For Internal use :

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Acacia Emulsion Unless otherwise specific, extemporaneously prepared emulsion for Internal use are made with acacia gum. To prepare acacia emulsions using a pestle and mortar, thin (primary) emulsion must be made first. The quantities for primary emulsions have been determined by experience and are given in Table-1

Table-1 Quantities for primary emulsions

Type of oil

ExampleQuantities for primary emulsions (parts)Oil Water Gum

Fixed Almond oilA rachis oilCastor oilCod-liver

4 2 1

Mineral Liquid paraffin 3 2 1Volatile Turpentine oil

Cinnamon oilPeppermint oil

2 2 1

Oleo-resin

Male fern extract

1 2 1

RxAlmond oil 50mlDouble strength chloroform water 100mlWater 200mlSent 100ml

Procedure:

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1) Almond oil is a fixed oil, therefore, the qualities for primary emulsion are (oil: water: gum =4:2:1)

Almond oil 25mlWater 12.5mlAcacia 6.25g

2) use the dry gum technique for Acacia Emulsion as follow

weigh the Acacia powder and place it in dry mortardispense the Acacia powder lightly in the wateradd 25ml oil at once and triturate until the primary emulsion is well established

the primary emulsion is then diluted with the remaining ingredients and transfer to measuring cylinder to adjusted volume with water.

3) Use amber dispensing bottle with a wide mouth4) Write label & add “shake the bottle before use” label.

Use: Demulcent and mildly laxative

2-Emulsions for External use :

White Liniment B.P

Rx after cal.Ammonium chloride 12.5g 0.625gDilute Ammonia solution 42ml 2.25mlOleic acid 85ml 4.25mlTurpentine oil 225ml 12.25mlpurified Water 625ml 31.25ml

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Sent 50ml

Calculation : factor = 50/1000 = 0.05

1. Make emulsifier (Ammonium Oleate) the reaction between dilute Ammonia and oleic acid as follow

a- Take 4.25 of Oleic acid & 12.5 of Turpentine oil and 2.2ml of Dilute Ammonia solution (2.5%) and 10ml of water.b- Shake vigorously to form TurpentineH2O emulsion

2. Dissolve 0.625g Ammonium chloride in the remaining water and mix it with to produce the preparation after adjusting the volume with H2O to 50ml3. Write label as follow :

Use : counter – irritant and rubefacient.

Calamine Lotion B.P.

RxCalamine 15g Zinc Oxide 5gBentonite 3gSod. Citrate 0.5gLiquid phenol 0.5gGlycerin 5mlPurified Water 100ml

Procedure:

1) Dissolve Sod. Citrate in 35ml Purified Water2) Weigh Calamine, Zinc Oxide and Bentonite & triturate it with

Sod. Citrate solution.3) Add Liquid phenol, the Glycerin and sufficient quantity of water

to make up the required volume. 4) Write LabelUse: Astringent & protective.

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Section (8)COSMOTIC PREPARATIONS

1- Cosmotic Creams :

Vanishing Cream B.P

RxStearic acid 120gOleic acid 40gGlycerin 50mlBoric acid 10gPotassium hydroxide 8gPurified Water Q.S 1000g

Sent 50g

Procedure:

1. Calculation factor = 50/1000 = 0.051. weigh all the ingredient accurately2. Mix the oily substance together and heat on water path.3. Mix the aqueous phase together and heat at the same water path with

stirring4. Dispense in container & shake well

Use: as protective when necessary 6. Make label

Acid conditioning Creams

RxCetyl alcohol 150gSod. Lauryl Sulfate 5gCitric acid 20gWater 825mlPerfume 0.3-0.5%

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Methyl Para hydroxyl benzoate

Sent 50g

Preparation:Factor = 50/1000 = 0.050

1. Calculate the intergradient 2. Melt to gather Cetyl alcohol with small portion of water.3. Prepare solution of Sod. Lauryl Sulfate with water4. Warm gently and with slow stirring to Cetyl alcohol5. Continue stirring to form stable cream 6. Finally add a solution of citric acid dissolved in the remaining

water.

Cold Cream

RxMineral oil 450mlBeen Wax 160gBorax 10gWater 380mlPerfume 0.3-0.5%Methyl paraben 0.12% { preservative}Propyl paraben 0.02% {preservative}

Sent 25g

Procedure:

1. Make the calculation (F= 50/1000)2. Heat to gather the Mineral oil & Been Wax to temperature

75OC3. In the separate container dissolve the borax in water and heat

to 75OC4. Add Borax slowly, with continuous stirring to oil/wax

mixture5. Cool with stirring, adding the perfume when temperature

reduced 35 OC.

35

Cleansing cream

Are basically cold creams slightly modified in some cases to be some what softer , to melt quickly and facilitate ease of application and spreading.The cream is effective cleansing agent and a thin residual film can be left on the skin when extra emolliency is required .

Rx

Mineral oil 500mlStearic acid 100 gLanolin 50 gTriethanolamine 12.5 gDistilled Water 337.5ml

Sent 50g

Preparation:

1. Make the calculation (F= 50/1000)2. Heat to gather the Mineral oil ,Stearic acid and Lanolin to temperature of 75OC3. In separate container dissolve the Triethanolamine in the water and heat to 75OC4. Add Triethanolamine solution slowly, with continuous stirring to Oil/Stearic acid/Lanoline mixture5. Cool with stirring,adding the perfume when temperature reduced 35 OC.

2- Shampoos :

Shampoo Paste or Creams

RxSod. Lauryl Sulfate 450gCetyl Alcohol 50gWater 500ml

36

Sent 25g

Preparation:1. Make calculation (f = 25/1000)2. Sod. Lauryl Sulfate is heated to gather with water to about

80OC(on water path).3. Add Cetyl Alcohol with stirring for about 15 min.4. the mixture is allowed to cool to about 40-45 OC.5. Add any perfume or colour ; stir to mix uniformly.6. pour it into the container while worm

Dandruff Shampoo

RxAlkyl trimethyl ammonia bromide(cetrimide) 150gCetyl Alcohol 150gWater 700ml

Sent 25g

Preparation:1. Warm gather Cetyl Alcohol & Alkyl trimethyl ammonia bromide (cetrimide)with 8ml Water.2. Stir gather until homogenous and add the remain Water to about 40OC3. Add perfume & colour & mix.

N.B. For use, the hair is first through wetted with warm water and about teaspoon of cream or lotion is managed well into the scalp with finger, the hair is then rinsed thoroughly and application repeated Finally the hair is thoroughly raised with warm water. Hair Conditioners

RxStearyl dimethyl benzyl ammonium Cl 35gCetyl alcohol 25gMineral Oil 5mlWater ` ` 935mlPerfume 0.3-0.5%Methyl Para hydroxyl benzoate 0.5%

37

Procedure:1. Melt together the fully materials and heat to 70-80 OC2. Dissolve Stearyl dimethyl benzyl ammonium Cl in water in a separate

container and to 70-80OC 3. Add the aqueous solution to the fully materials while stirring slowly to

avoid air entrapments.4. Continue cooling at about 35OC

3- Make–Up Preparations :

Lipsticks

The lipsticks consist of coloring material dispensed and suspended in a base prepared from a blend of a oils and waxes adjusted to yield the desired melting point and viscosity. The most appropriated melting point range is 55-75 OC.

38

RxCarnuba Wax 10g Bees Wax 15gLanolin 5gCetyl alcohol 5gCastor Oil 65gPigment (Sudan III)Perfume

Sent 25g

Procedure:1- Melt together Carnuba Wax, Bees Wax, Lanolin and Cetyl

alcohol on a water path .2- Heat Castor Oil in separated container to 75OC and then

dissolve the required amount of Sudan III (or caramine as Pigment) which give the desired red or pink colour respectively.

3- Add Castor Oil, Pigment solution while it is hot on the melted base and mix well.

4- Pour into the mould after adding the Perfume and leave to cool.

Eye Make-up

Cosmetic preparations for the eye are now an inertial feature of the facial make-up, assuming as much important as the use of lipsticks. Eye shadows are prepared in wax base as creams, in stick form, as loose powder, or as compressed powder.

39

Emulsion type eye shadow:

RxStearic acid 16gTriethanolamine 4mlPetrolatum 25gLanolin 5gPropylene glycol 5gWater 45mlPigment Q.SPerfume Q.S

Sent 20g

Procedure:1. Make the calculation (F= 20/1000 = 0.2)2. Melt and heat Stearic acid, Petrolatum, Lanolin to70OC3. Mix Triethanolamine, Propylene glycol and water and to 70OC4. Add aqueous phase to the oily phase with continue stirring.5. Remove from bath and stir until complete cooling (add Perfume

at 35 OC.

N.B:The Pigment is dissolve in aqueous phase if is water soluble and in oily phase if it is oily soluble before mixing.

Preparation of Deodorant Stick

RxStearic acid 3.4gSod. hydroxide 0.6gDistilled Water 1.0mlGlycerol 7.5gCetrimide 0.75gEthanol 75mlPerfume Q.S

40

Sent 20g

Procedure:1. Melt Stearic acid at 75-80OC2. Dissolve Sod. Hydroxide and Cetrimide in water –Glycerol

mixture, heat at 75-80OC 3. Add ½ quantity of ethanol to the melt Stearic acid, stir to dissolve

.4. Add gradually solution (2) to Stearic acid solution with stirring,

wash the container of Sod. Hydroxide, Cetrimide solution with second ½ of Ethanol and add to Stearic acid solution. This step should take about 5 times to avoid excessive volatilization of Ethanol.

5. White mixing on water – bath add Perfume, remove from heat and quickly pour onto the stick container.

Section (9)POWDERS

1- Properties of powders :

The word "powder" refers to a chemical or mixture that is solid in physical state. In compounding, "powder" refers to a dosage formulation that is solid in physical state. But the formulation may be composed of only the active drug or may be a mixture of the active drug and other ingredients.

41

Powders offer some unique advantages: each dose can contain a different amount of active drug can be administered easily to infants and young children who cannot

swallow tablets or capsules drug will have a rapid onset of action since disintegration is not

required can be applied to many body cavities such as ears, nose, tooth socket,

throat drugs tend to most stable as a solid can be made into many different dosage formulations (capsules, tablets,

powders for reconstitution, dusting powders, bulk powders, powders for inhalation, etc.)

Pharmaceutical powders are formulated to be exist as fine particles. The powders are then smooth to the touch and nonirritating to the skin. Powders generally range from 0.1 to 10 micron in size. The size of the particles are often expressed as a number which corresponds to the mesh screen size of a sieve. The screen size indicates the number of openings in the mesh screen per inch. For example, a # 40 sieve has 40 openings per inch in the screen mesh. Particles that can sift through that mesh are said to be "40 mesh" size.

Below is a list of mesh sizes and the size of the mesh opening in millimeters (1/1000 of a meter) or microns (1/1,000,000) of a meter. Of coarse there is a correlation between the size of the mesh opening and the particle size of the sifted powder. As the opening becomes smaller, so will be resulting particle size. Most of the particles of a sifted powder will have approximately the size as the mesh opening.

Mesh Opening SizeMesh Size Number

millimeters microns

2 9.52 95204 4.76 47608 2.38 238010 2.00 200020 0.84 840

42

30 0.59 59040 0.42 42050 0.297 29760 0.250 25070 0.210 21080 0.177 177100 0.149 149120 0.125 125200 0.074 74

The USP 24/NF19 uses descriptive terms to define powder fineness. The table below shows the correlation their classification

Description Term Mesh Opening Size (microns) Mesh Size NumberVery Coarse > 1000 2 – 10

Coarse 355 -1000 20 – 40Moderately Coarse 180 – 355 40 – 80

Fine 125 – 180 80 – 120Very Fine 90 - 125 120 - 200

A good powder formulation has an uniform particle size distribution. If the particle size distribution is not uniform, the powder can segregate according to the different particle sizes which may result in inaccurate dosing or inconsistent performance. A uniform particle size distribution insures an uniform dissolution rate if the powder is to dissolve, an uniform sedimentation rate if the powder is used in a suspension, and minimizes stratification when powders are stored or transported.Reducing the particle size of a powder will result in an uniform distribution of particle sizes. The process of reducing the particle size is called comminution. In extemporaneous compounding, there are three methods of comminution:

Trituration is the continuous rubbing or grinding of the powder in a mortar with a pestle. This method is used when working with hard, fracturable powders.

Pulverization by Intervention is used with hard crystalline powders that do not crush or triturate easily, or gummy-type substances. The first step is to use an "intervening" solvent (such as alcohol or acetone) that

43

will dissolve the compound. The dissolved powder is then mixed in a mortar or spread on an ointment slab to enhance the evaporation of the solvent. As the solvent evaporates, the powder will recrystallize out of solution as fine particles.

Levigation reduces the particle size by triturating it in a mortar or spatulating it on an ointment slab or pad with a small amount of a liquid in which the solid is not soluble. The solvent should be somewhat viscous such as mineral oil or glycerin. This method is also used to reduce the particle size of insoluble materials when compounding ointments and suspensions.

2- Classification of powders:

Bulk Powders: Bulk powders are nonpotent and can be dosed with acceptable accuracy and safety using measuring devices such as the teaspoon, cup, or insufflator. This practically limits the use of orally administered bulk powders to antacids, dietary supplements, laxatives, and a few analgesics. Many bulk powders are used topically.

Douche Powders:

Douche powders are used to prepare solutions that cleanse the vagina. Most douche powders are used for their hygienic effects, but a few contain antibiotics.Douche powders are prescribed as a matter of convenience for the patient, since a powder is more portable than a bulky solution. The formula is developed so that a teaspoonful or tablespoonful of powder dissolved in a specified volume of water provides the desired concentration. The pH usually ranges from 3.5 to 5 when the solution is prepared. Feminine bulb syringes or fountain syringes are used for vaginal irrigation. Since many of the ingredients are volatile (e.g., menthol, thymol, and volatile oils), douche powders should be packaged in glass jars with a wide mouth. Some commercial douche powders are available in metal foil packets, which contain the proper amount of powder for a single douche. Many douches are also available as prepared unit of use solutions in disposable applicators.

Insufflations:

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Insufflations are extremely fine powders to be introduced into body cavities. To administer an insufflation, the powder is placed in the insufflator, and when the bulb is squeezed, the air current carries the fine particles through the nozzle to the region for which the medication is intended. All extemporaneously compounded insufflations must be passed through a 100 mesh sieve. Pressurized packages provide an elegant approach to the administration of insufflations.

Powder Sprays: In contrast to dusting powders, powders dispensed under pressure will deliver targeted and uniform application at the desired site. Also, in an aerosol container medicated powders may be maintained in a sterile condition. The powder particles must be a definite size range to prevent clogging of the valve orifice and to provide uniformity of application. In general, powders that are to be packaged as powder sprays must not contain particles greater than 50 microns if they are to be sprayed successfully.

Preparation of divided powder

Divided powders or charts are single doses of powdered medicinals individually wrapped in cellophane, metallic foil, or paper. The divided powder is a more accurate dosage form than bulk powder because the patient is not involved in measurement of the dose. Cellophane and foil-enclosed powders are better protected from the external environment until the time of administration than paper-enclosed powders. Divided powders are commercially available in foil, cellophane or paper packs.

45

All drugs are reduced to a fine state of subdivision before weighing , the weighed powders are blended by geometric dilution or mixing in ascending order of amount.

Rx

Magniesium trisilicateTribasic calcium phosphateActivated charcoal aa 0.19 G

Fiat, pul. , mitte IV

SIG.: One Chartula T.I.D.P.C.

Use : Antacid ,antiflatulent .

Procedure:

1. Mix the ingredients to full homogenity.2. Divided as mentioned above ( by weighing ).3. Fill in packets as follows :

a- Fold down 1 cm margin from the weighing paper .b- Distribute the divided dose over the paper c- left and fold the lower end of the paper until it lies exactly in the

crease of the original top fold.d- Make additional fold.e- Bring the two ends to each other dividing the paper to three equal

parts .

Preparation of dusting powder

Dusting powders are fine medicinal (bulk) powders intended to be dusted on the skin by means of sifter-top containers. A single medicinal agent may be used as a dusting powder; however, a base is frequently used to apply a medicinal agent and to protect the skin from irritation and friction. Bentonite, kaolin, kieselguhr, magnesium carbonate, starch, and talc are used as inert bases for dusting powders. Powder bases absorb secretions and exert a drying effect, which relieves congestion and imparts a cooling sensation. All extemporaneous dusting powders should be passed through a 100-200 mesh

46

sieve to ensure that they are grit free and will not further mechanically irritate traumatized areas.

Rx

Camphor 0.1 GStarch 0.6 GZinc 0.3 G

Send 20 G

Sig. : To be used U.D.

Use : Counter irritant.

Procedure:

1- Weigh the camphor and try to pulverize in the mortar with pestle2- Add few drops of alcohol and pulverize .3- Mix starch and zinc oxude and gradually add to camphr while

trituration until uniformity .4- pass through 90-mesh sieve.

Section (10)GRANULES

Granules are particles ranging in size from about 4 to 10 mesh. Granules generally are made by first blending the powders together and then moistening the mixture to form a pasty mass. The mass is passed through a sieve and then dried in air or in an oven. They are prepared as a convenience for packaging, as a more stable product due to less surface exposure, and as a popular dosage form. Granulations are also used as intermediates in the preparation of capsules and tablets, since they flow more smoothly and predictably than do small powder particles.

47

The most popular compounded granulation is the effervescent powder (sometimes called effervescent salts). These granulations are popular due to their taste and psychological impression. When added to water, the granulation effervesces ("fizzes") as carbon dioxide is liberated.

Methods of preparation :

There are two methods of preparation of granules :- Dry fusion method - Wet method

Fusion method:

In the fusion , the one molecule of water present in each molecule of citric acid acts as the binding agent for the powder mixture . After weighing the required amount of powder \s they are mixed together to ensure the uniformity of the mixture. Then the powder is placed on a porcelain dish on boiling water bath and stirred with the help of a glassRod . The heat causes the release of the water of crystallization from the citric acid which in turn dissolves a portion of the powder mixture, setting of the chemical reaction and the consequent release of some carbon dioxide. This causes the sofened mass of powder to become somewhat spongy, and when of the proper consistency as bread dough ,it is removed from the oven and rubbed through an acid resiste=ant sieve to produce granules are dried at temperature not more than 54 – 60 o c and transferred to containers which are then promptly and tightly sealed . the fused method is used in the preparation of most commercial effervescent powder .

1-Preparation of some granulating agents and preparation of simple granulation by wet method :

Procedure:1. Prepare the binders by the appropriate method:

Starch paste: add the starch slurry dropwise to boiling water while

48

keeping stirring with a glass rod. Soak the polymer (Methyl cellulose in warm water) for about 10 min. and start solution process by stirring while heating (methyl

cellulose dissolve while keeping cold in an ice-bath).2. Mix the antacid powder with appropriate amount of the binder in the palnetary mixer till the formation of a cohearent mass.3. Sieve the mass by through the oscillating granulator.4. Dry the obtained granules in an oven at 50-60ºC.

2-Preparation of Effervescent Granulation :

It has been found that citric acid monohydrate and tartaric acid used in the ratio of 1:2, respectively, produces a powder with good effervescent properties. Citric acid monohydrate is not used alone because it results in a sticky mixture that will not easily granulate. Tartaric acid is not used alone because the granules are too friable and crumble. The amount of sodium bicarbonate to be used may be calculated from the reaction which occur when the granules come in contact with water. The reaction equation between citric monohydrate and sodium bicarbonate is given below:

Setting up a proportion to determine the amount of sodium bicarbonate that will react with 1 gm of citric acid, one has:

49

Similar calculations show that 2.24 gm of sodium bicarbonate react with 2 gm of tartaric acid

Thus, with the acids in a ratio of 1:2, it has been calculated that 3.44 g (1.2 g + 2.24 g) of sodium bicarbonate is necessary to react stoichiometrically with the 3 g of combined acids. To enhance the flavor, the amount of sodium bicarbonate may be reduced to 3.4 gm to allow for a small amount of unreacted acid to provide a tart taste.The ratio of two acids should be sdjusted as excess tartaric acid will lead to tough mass , while excess of citric acid will lead to soft mass .

The liberated carbon dioxide has the following advantages :- It masks the bitter and naseaous taste.- It promotes gastric secretions.- It acts as a carminative.

Preparation of granules using Wet method :

1- all powders are dried to constant wt. At temp. 100-105 o c .2- pulverize each powder through sieve No.90 weigh the calculated amount

separately.3- Pass the pulverized powder through sieve No. 90 and weigh the

calculated amount from each powder separately .

50

4- Mix the powder together and by the aid of alcohol 96 % ( drop adding ) make the mass coherent between your fingers and the mixing is continued until the mass will retain its shape when moulded into a ball .

5- The mass is forced through sieve No. 10 then dry in ovens at temp. not exceeding 50 O C .

6- After drying the granules sieved through sieve No. 20 to leave the fine particles, and packed in well closed wide mouth bottles.

Calculation :

Calculate for slight excess due to the mechanical loss ( loss arised from handling the materials and during the preparation ) and the chemical loss ( arised from liberation of CO2 & H2O , the chemical loss nearly equals to 1/7 formula).

Prepartion of sodium citra tartarate ( B.P.C.)

Rx

Sodium bicarbonate 510 gTartaric acid 270 gCitric acid 180 gSucrose 150 g

These amounts of the ingredient base will give 1000 g only , thus 110 g which is lost due to liberated CO2 & H2O ( chemical lss).

For calculation:- mechanical loss ( lies between 15-20% ) , so,- for mechanical loss we take ( (25 x 20 ) / 100 + 25 ) = (5+25) = 30 g. from the base.

- for NaHCO3 (30 x 510)/1000 =15.3 g

- Tartaric (30 x 2700)/1000 = 8.1 g

- Citric acid ( 30 x 180 )/1000 = 5.4 g

- Sucrose (30 x 150)/1000 = 4.5 g

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Total = 33.3 g Thus 33.3 g is the total amount of ingredient after adding the amounts which can loose during handling and during chemical reactions.

If the amount of sodium bicarbonate is not known , calculate it as follows

Amount of Sod. Bicarbonate =

( amount of citric acid x Eq. wt. Of sod. bicarb.) / Eq. wt. Of citric acid +( amount of tartaric acid x Eq. wt. Of sod. bicarb.) / Eq. wt. Of tartaric acid

= ( (180 x 84)/70 + (180 x 84)/75 ) = 519.4

- In the prescription the amount used is 510 g so the final solution will slightly acidic.

Section (11)TABLETS

1-Introduction : Without question, the compressed tablet is one of the most popular dosage forms today. About one-half of all prescriptions dispensed are for tablets. Usually one considers a compressed tablet as an oral medication; however, tablets have many other uses. The sublingual tablet, the pellet, the wafer, the troche, and the vaginal insert are manufactured by the same procedure as an oral tablet.

52

Tablets contains certain excipients selected to aid the processing and improve the properties of the product .

Tablet Excipients :

1) Fillers : used to increase the bulk of the tablet . it is generally not feasible to make tablets with a weight of loss than about 70 mg. It is essential that fillers be inert and stable .

A - Soluble : lactose , sucrose , mannitol , sorbitol .

B – Insoluble: calcium sulphate , dicalcium phosphate , tricalcium phosphate , starch , calcium carbonate .

2) Binders : the substance that glue powders together and cause them to form granules are the bimders or adhesives. They are either sugars or polymeric materials.

Examples

- Water ,

- Ethanol ,

- Acaccia mucilage (10-20%) and it gives hard ,friable granules ,

-Tragacanth mucilage (10-20%) ,

- Gelatin solutions (2-10%) , they are strong sdhesive ,use warm.

-Starch mucilage (5-10 %) , one of the best general adhesieves ,use warm.

- Glucose syrup (25-50%) , strongly adhesieve , tablet may soften in high humidity

- PVP (3-15%) - Cellulose derivative (5-10 %)

3) Lubricants ,glidents and anti – adherents :

Three of the problems associated with tablet manufacture are the flow of granulation , the adhesion of material to the punches and dies , and release of the tablet from the press.

Lubricants :

Are those agents that the friction between the tablet edge and die wall during the ejection cycle . e.g. magnesium stearate - Lubricants are usually

53

added at the very last step before compression , since they must be present on the surfaces of the granules between them and the parts of the tablet press .

Glidants :

Are materials that improve the flow characteristics of granulation e.g. talc.

Anti – adherents :

Function to prevent tablet granulation from sticking to faces of the punches and the die walls e.g. talc .

Disintegrants :

Is a term applied to substance added to a tablet granulation for the purpose of causing the compressed tablet to break apart when placed into an aqueous environment .

Method of adding disintegrant :

It is better to add it in two portions , one half is added to the powdered components before the wet granulation process and the remaining portion is added to the finished granulation just prior to the compression . This method hold that a disintegrent is required between the granules as well as within them Some of the commonly used disintegrant

- Starch (5-20% w/w )

- Avicel (5-20 % w/w)

- Algenic acid (5-10 %w/w)

- Veegum (5-15 % w/w)

- Bentonite ( 5-15 % w/w)

Single-punch Tablet Machines

Tableting machines are commonly used in pharmaceutical industry. They are high-speed machines that create thousands of tablets in a small period. The compounding pharmacist uses a variation of these machines. It is called a single-punch tablet press and makes one tablet at a time. A "punch" has two pieces of casted tubular metal. The bottom metal piece has a small cavity in one end of the tube; the top metal piece has one end that is tapered into a small

54

rod that will just fit into the small cavity in the other piece. The rod does not go all the way to the bottom of the cavity, but leaves a small gap. The punch is fitted into a press so that when the handle is depressed and released, the rod goes into and then comes out of the bottom piece. To make a tablet, the powder material is placed into the bottom piece, and the handle is depressed and released. The powders are compressed and occupy the size of the gap designed in the punch.

Punches come in many sizes which allows the production of tablets of different sizes and compression strengths. But each punch is a matched set; it is not possible to interchange the top and bottom pieces of different punches.

Chewable tablets, effervescent tablets, and compressed tablets can be made using a tablet press. Chewable tablets are generally made using mannitol because it has a sweet, cooling taste and is easy to manipulate. Other ingredients may include binders (e.g., acacia), lubricants (e.g., stearic acid), colors, and flavors. The powder mixture is prepared, the desired quantity of mixture is weighed, and then pressed with a single-punch tablet machine.

Effervescent tablets generally contain ingredients such as tartaric acid, citric acid, and sodium bicarbonate. These powders would be appropriately mixed and pressed into tablets using the same procedure as chewable tablets. They will not require a disintegrant since they will effervesce when placed in water. Compressed tablet mixtures generally contain the active drug, a diluent (e.g., lactose), a disintegrant (e.g., starch), and a lubricant (e.g., 1% magnesium stearate).

There are three methods of commercially making compressed tablets :

a) The direct compression method

A compressible vehicle is blended with the medicinal agent, and if necessary, with a lubricant and a disintegrant, and then the blend is compressed. Substances that are commonly used as directly compressible vehicles are: anhydrous lactose, dicalcium phosphate (Emcompress), granulated mannitol, microcrystalline cellulose (Avicel), compressible sugar (Di-Pac), starch (Sta-

55

Rx 1500), hydrolyzed starch (Celutab), and a blend of sugar, invert sugar, starch and magnesium stearate (Nutab).

Preparation of Aspirin tablet by direct compression

Ingredient Composition Quantity per tab.(mg)

Quantity per 100 tab.

(g)

Aspirin (granular) (mesh 40)

Starch (Disintegrant)

Talc (Glident )

Srearic acid

Total Tablet Weight

90%

7%

2.4%

0.6%

325

25

9

2

361

32.5

2.5

0.9

0.2

Procedure :

1) Screen aspirin on 40 mesh sieve to remove the fine particles.

2) Blend all the ingredients in a mortar using plastic spatula.

3) Compress into tablets using 9 mm standard concave punches.

b) The dry granulation method (slugging method)

The ingredients in the formulation are intimately mixed and precompressed on heavy duty tablet machines. The slug which is formed is ground to a uniform size and compressed into the finished tablet.

However, when direct compression is not possible due to the properties and those of the drug ,and wet granulation cannot be used because the drug is

56

sensitive to mositure and heat, then dry granulation remains the only method available.

Preparation of Aspirin tablet by dry granulation

Ingredient Composition Quantity per tab.(mg)

Quantity per 100 tab.

(g)

Aspirin (fine powder)

Starch (Disintegrant)

Talc (Glident )

Srearic acid (lubricant)

Total Tablet Weight

90%

7%

2.4%

0.6%

325

25

9

2

361

32.5

2.5

0.9

0.2

Procedure :

Mix all the above ingredients (except) 50 % of starch, talk and magnesium stearate.

Compress into slug using 18 mm flat face punishes.

Grind the slugs using 20 mesh screen.

Transfer into cubic mixture and the reminder disintegrant and lubricant, mix for 10 minutes.

Compress to weight using 9 mm concave punishes.

C) The wet granulation method

This method has more operational manipulations, and is more time-consuming than the other methods. The wet granulation method is not suitable for drugs which are thermolabile or hydrolyzable by the presence of water in the liquid binder. The general steps involved in a wet granulation process are:

57

The powdered ingredients are weighed and mixed intimately by geometric dilution.

The granulating solution or binder is prepared.

The powders and the granulation solution are kneaded to proper consistency.

The wet mass is forced through a screen or wet granulator.

The granules are dried in an oven or a fluidized bed dryer.

The dried granules are screened to a suitable size for compression.

A lubricant and a disintegrating agent are mixed with the granulation.

The granulation is compressed into the finished tablet.

Preparation of Chewable antacid tablets

Ingredient Quantity per tab.(mg)

Quantity per 100 tab.

(g)

Aluminum Hydroxide

Calcium Carbonate

Mannitol

Gelatin ( as 10% solution)

Magnesium Stearate

Talc

Oil of Peppermint

Total Tablet Weight

300

150

100

20

15

15

0.2

600

30

15

10

Procedure:

1) Mix the first three ingredients and moisten with a 10 % gelatin solution until formation of coherent mass.

2) Granulate by passing through 10 mesh screen.

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3) Dry at 50o

C. Overnight, screen the drug granules through 20/35 mesh.

4) Add the oil of peppermint mixed with talc and finally the magnesium searate.

5) Mix for 5 minutes in a cubic mixer.

6) Compress using 12 mm flat face punishes.

2- Evaluation Of Tablets :

Tablets are evaluated by a variety of methods.

A. Unofficial tests :

Tablet hardness: The tablets must be hard enough to withstand mechanical stress during packaging, shipment, and handling by the consumer. Section <1216> of the USP 24/NF19 outlines a standard tablet friability test applicable to manufactured tablets. Most compounding pharmacy would not have the apparatus specified in Section <1216>. However, there are several hand operated tablet hardness testers that might be useful. Examples of devices are the Strong Cobb, Pfizer, and Stokes hardness testers. The principle of measurement involves subjecting the tablet to an increasing load until the tablet breaks or fractures. The load is applied along the radial axis of the tablet. Oral tablets normally have a hardness of 4 to 8 or 10 kg; however, hypodermic and chewable tablets are much softer (3 kg) and some sustained release tablets are much harder (10-20 kg).

Determination of Tablet Hardness

Using a hardness tester ( Erweka ) , determine the hardness of the four (4) different types of tablets supplied. Use an average of three measurements for each determination and comment on your results.

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Hardness Tester _______________

Tablet Type

Hardness 1 Hardness 2 Hardness 3Mean

Hardness

       

       

       

       

Comment on Results

Friability Test : This test is designed to measure the ability of the tablet to withstand handling and transportation.

Procedure : ( using Roche Friabilator ):

1. Take 20 tablets dedust and weigh them (wo)

2. Place tablets in friability drum , switch on the apparatus adgusting the timer to 4 min. , and the speed at 25 r.p.m.

3. At the end of thid operation the tablets are removed , dedusted and re- weighed (w) . should any tablet break the batch is rejected .

4. Friability B is expressed as a percentage loss in weight :

B =100 (1 - (w/wo ) )

5. If value of B is 1.0 % or less , the batch is accepted .

B. Official standards :

Weight Variation

The total weight of a tablet is determined by the depth of the die cavity, bulk density of granules or powder, and uniformity of particulate flow.

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Even with a proper granulation having uniform flow, a volume fill is not as accurate as a fill based on weight. Therefore, tablet weight variations must fall within certain specifications established by the USP.

Tablets are required to meet a weight variation test where the active ingredient comprises a major portion of the tablet , tablets containing 50 mg or less of active ingredients , comprising less than 50% by weight of the tablet should pass a content uniformity test.

Procedure :

Select 30 tablets and proceeds as follows :

1) Weigh accurately 10 tablets indiidually and calculate the average weight .

2) Calculate the average value of drug content as % following the asay procedure using another sample obtained from the same batch .

3) Calculate the relative standard deviation (RSD)

Tablet# Weight of Tablet

(mg) %Labeled

Claim1  

2  

3  

4  

5  

6  

7  

8  

9  

10  

Note: Labeled claim is 750 mg

Mean (as % of labeled claim)_________

Standard Deviation __________

RSD __________

( Assay procedure of Aspirin tablets : )

Powder 10 tablets , weigh 0.5 g of powdered tablets , put in conical flask , add 25 ml of 0.5 N NaOH , boil gently for 5 min. , cool and titrate excess alkaline with 0.5 N HCL using phenol red as indicator

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- Each ml of 0.5 N HCL is equivalent to 0.045 g Aspirin

- Repeat the operation without aspirin

- Amount of Aspirin = ( B – Exp. ) x 0.045 = A

- % of Aspirin in tab. =( A / 0.5 ) x 100

(average content )

4) Calculate the content of active ingredient

in each 10 tablets = tab. Wt. X average content

100

Content Uniformity

NOTE: Tablets should be analyzed in the same order as the weight variation test so that a comparison between weight variation and content uniformity can be made.

Determine the content of active ingredient of the tablets by the procedure given below.

- Select 30 tabs and proceed as follows :

- Assay 10 tablets individually as directed in the assay in the individual monograph unless otherwise specified in the test for content uniformity

- Calculate RSD as befor.

Criteria : ( apply the following criteria , unless otherwise specified in the individual monograph )

A) If the average of the limits specified in the potency definition in the individual monograph is 100 % or less :

For weight variation , or content uniformity :

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The requirements are met if the amount of the active ingredient in each of 10 tablets tested lies within the range of 85 % to 115 % of the label claim and relative standard deviation is less than or equal to 6.0% .

If one tablet is outside the range of 85% to 115 % of the label claim and no tablet is outside the range of75 % to 125 % of the label claim or if RSD is greater than 6 , or if both conditions prevail , test 20 additional units the requirements are met if not more than one tablet of the 30 is outside the range of85 % to 115 % if the label claim and no tablet is outside the range of 75 % to 125 % of the label claim and RSD of the 30 tablets does not exceed 7.8 % .

B) If the average of the limits specified in the potency definition in the individual monograph is greater than 100 % :

1. If the average value of the tablets tested is 100 % or less , The requirements are as in (A) .

2. If the average value of the tablets tested is greater than or equal to the average of the limits specified in the potency definition in the individual monograph , the requirements are as in (A) . except that the word s “ label claim “ are replaced by the words “label claim multiplied by the average of the limits specified in the potency definition in the individual monograph is divided by 100 “ .

If the average value of the tablets tested is between 100 % and the average of the limits specified in the potency definition in the individual monograph , the requirements are as in (A) , except that the word s “ label claim “ are replaced by the words “label claim multiplied by the average value of the tablet tested ( expressed as % of label claim ) divided by 100 “

Tablet disintegration: is an essential attribute for tablets intended for administration by mouth , except those intended to be chewed before being swallowed and except some types of sustained release tablets.

Disintegration (for uncoated tablets )

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This test is provided to determine compliance with limits on disintegration stated in the individual monograph . Disintegration does not imply complete solution of the tablet or even its active constituent .

Complete disintegration is defined as that state in which any residue of the tablet remaining on the screen of the test apparatus is a soft mass havong no palpably firm core.

Procedure:

1. Place one tablet in each of the six tubes of the basket , add a disk to each tube

2. Operate the apparatus , using water maintained at (37+2) o C . as the immersion fluid unless another fluid is specified in the individual monograph .

3. At the end of the time limit specified in the individual monograph , left the basket from the fluid ,and observe the tablets : all of the tablets have disintegration completely . if one or two tablets fail to disintegrate completely , repeat the test on 12 additional tablets : not less than 16 of the total of 18 tablets tested disintegrate completely .

Apparatus : refer to USP for details.

Tablet dissolution: Disintegration time determination is a useful tool for production control, but disintegration of a tablet does not imply that the drug has dissolved. A tablet can have a rapid disintegration time yet be biologically unavailable. The dissolution rate of the drug from the primary particles of the tablet is the important factor in drug absorption and for many formulations is the rate-limiting step. Therefore, a dissolution time is more indicative of the availability of a drug from a tablet than the disintegration test. Even though this is an important parameter to measure.

Place the stated volume of dissolution medium in the vessel of the apparatus specified in the individual monograph, assemble the apparatus, equilibrate the dissolution medium to 37 + 0.5 o C and remove the thermometer. Place one tablet in the apparatus, and operate at the specified rate of the monograph. At

64

the time specified, withdraw a sample and perform the analysis as in the monograph. Repeat the test with additional tablets.

Unless otherwise specified in the individual monograph and the requirements are met if the quantities of active ingredient dissolved from the tablets tested conform to the accompanying acceptance table.

ACCEPTANCE TABLE

Stage Number Tested

Acceptance Criteria

S1

S2

S3

6

6

12

Each Tablet is not less than Q + 5%

Average of 12 tablets (S1+S2) is equal to or greater than Q, and no unit is less than Q-15 %

Average of 24 tablets (S1+S2+S3) is equal or greater than Q and not more than two tablets are less than Q-15%

Continue testing through the three stages unless the results conform at either S1 or S2. The quantity Q, is the amount of dissolved active ingredient specified in monograph expressed as a percentage of the labeled content. Both the 5% and 15% value in the acceptance table are percentages of the labeled content.

Dissolution Test For Aspirin Tablets (Uncoated)

- Medium : 0.05 M acetate buffer having pH of 4.5; 500ml

- Time : 30 min

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- Q : 75 %

Assay Procedure :

1) At the time specified, 2 ml aliquote is pipetted out through a Millipore filtration unit and placed in a 50 ml volumetric flask. Then add 2 ml dissolution medium to the dissolution vessel.

2) After adjusting volume to 50 ml with 0.1N sulphuric acid, the absorbance of each solution is measured at 228 nm.

3) The amount of Aspirin dissolved ( C ) =

(Absorbance X Conc.Factor X Dil Factor X Dissolution Medium Volume) = (Absorbance X 0.02 X 25 X 500 ) mg.

4) Percentage of Aspirin dissolved at time specified =

5) C/ Label Claim X 100 = C/325 X 100

Section (12)CAPSULES

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1- Introduction : Capsules are gelatin shells filled with the ingredients that make up an individual dose. Dry powders, semi-solids, and liquids that do not dissolve gelatin may be encapsulated. Capsules account for about 20% of all prescriptions dispensed. Capsules have several advantages as pharmaceutical dosage forms:

1. They may be used to mask the unpleasant tastes, aromas, or appearance of a drug. 2. They allow powders to be dispensed in an uncompressed form, thus allowing for quicker dissolution and absorption of the drug following oral dosing (as compared with tablets). 3. They offer the pharmacist versitility to prepare any dose desired for a variety of administration routes (e.g. oral, inhalation, rectal, or to be diluted for vaginal, rectal, oral or topical use). 4. They may be easier than tablets for some people to swallow. 5. They can be make to alter the release rate of the drug.

Their disadvantages or limitations include the following: They are easily tampered with (although techniques exist for preventing

this). They are subject to the effects of relative humidity and to microbial

contamination. They may be difficult for some people to swallow. More expensive (commercially).

HARD GELATIN CAPSULES

The hard gelatin capsule consists of a base or body and a shorter cap, which fits firmly over the base of the capsule. For human use, eight sizes of capsules are available. The capacity of each size varies according to the combination of drugs and their apparent densities. Capsules are available as clear gelatin

capsules or in a variety of colors. The pharmacist can use the different colored

67

capsules to distinguish two capsule formulations for the same patient, or to encapsulate unattractive ingredients. The pharmacist can add a dye to the powder before filling a clear capsule to impart a color for identification or esthetics.

Some types of hard gelatin capsules have a locking cap, which makes it more difficult to reopen the capsule.

To aid in the selection of the appropriate size, a table, with the capacity of five common drugs for that particular size capsule, is printed on the box of the capsules. As a guide, the relative sizes and fill capacities of capsules are given below. By knowing the bulk density of fill material, proper choice of capsule size is usually made easier; however, trial and error soon develops the judgment of the beginning pharmacist.

Capsule Size Volume ( ml) Mg of Lactose Mg of Aspirin000 1.37 1340 100000 0.95 929 6000 0.68 665 5001 0.50 489 3002 0.37 362 2503 0.30 293 2004 0.20 195 1255 0.13 127 60

2- Methods of preparation of capsules :

"Punch" Method

To hand fill capsules at the prescription counter, the pharmacist generally uses the "punch" method. The ingredients are triturated to the same particle size and then mixed by geometric dilution. The powder is placed on a powder paper or ointment slab and smoothed with a spatula to a height approximately half the length of the capsule body. The base of the capsule is held vertically and the open end is repeatedly pushed or "punched" into the powder until the capsule is filled; the cap is then replaced to close the capsule. Each filled capsule is weighed using an empty capsule as a counterweight. Powder is added or removed until the correct weight has been placed in the capsule. The filled capsule is tapped so that no air spaces are visible within the contents.

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It is a good practice to remove from the stock container the exact number of empty capsules needed before you begin filling them. In this way you avoid preparing the wrong number of capsules and at the same time avoid contaminating the empty capsules with drug particles that cling to your hands. Also, since some fill material will likely be lost in the process of punching capsules, the pharmacist generally calculates for the preparation of at least one extra capsule to insure enough fill for the last capsule.The simplest method by which a capsule may be kept free of moisture during compounding is to wash the hands well, dry them, and keep the fingers dry by stripping a towel through the cleansed fingers until warmth is felt. An alternative method is to use the base of one capsule as a holder for other bases during the filling operation. The capsules do not come in contact with the fingers. The most sure method of protecting the capsule is to wear finger cots or rubber gloves.

Capsule Machines

Capsule machines are available for filling 50, 100, and 300 capsules at a time. Each manufacturer's machine is slightly different in its operation, but the series of operations is the same. Capsules are first loaded into the machine. Most machines come with a capsule loader which correctly aligns all of the capsules in the machine base. There are plates on the machine base that can be adjusted. First, the plates are adjusted to hold the capsule bodies in place while the caps are removed all at one time. The caps remain in place in the top of the machine for later use. Then the plates are adjusted again so that the capsule bodies will "drop" into place so that the tops are flush with the working surface of the plate.

The formulation powder is poured onto the plate and special spreaders and combs are used to fill the individual capsules. Some manufacturer's have special shakers that will also help spread the powder and fill the capsules. The powder is spread evenly over the plate, and the comb is used to tamp and pack the powder into the capsules. These two processes are repeated over and over again until the capsule bodies are filled with the powder. All of the caps are then simultaneously returned to the capsule bodies, and the closed capsules are removed from the machine.

69

The machine has the advantage of filling many capsules in a timely manner. However, there is a tendency to pack the capsules in the middle of the plate with more powder than the capsules along the periphery. It takes practice to ensure that each capsule has the same amount of drug. A quality control procedure should be executed with each batch of capsules produced with the machine.

Final Processing Once the capsules have been compounded and the capsule closed, the pharmacist may want to "seal" the capsule. The best way is to use "locking" capsules, where the body and cap lock together, making it very difficult to open the capsule again. If using locking capsules, during the filling process the cap is not completely closed onto the body in the weighing procedure to determine the weight of powder in the capsule. The locking is done only one time and that is after the capsule is correctly filled. If locking capsules are not used, a seal can be made by touching the outer edge of the body with a moist towel to soften the gelatin. Alternatively, a cotton swab dipped in warm water can be rubbed around the inner edge of the cap. When the cap is closed on the body, it is slightly twisted to form the seal.

When compounding and sealing are complete, the capsules may need cleaning to remove fingerprints, traces of body oils, or loss powder from the capsule. Fingerprints and oils cannot be effectively cleaned from capsules so the best way to prevent these problems is to wear gloves during the compounding process. Any clinging powder can be removed by rolling the capsules between the folds of a towel. Another proposed cleaning method is to put the capsules in a container filled with sodium bicarbonate, sugar, or sodium chloride, and gently roll the container. Then the container contents can be poured into a ten-mesh sieve where the "cleaning salt" will pass through the sieve.

Capsules should be visually inspected and checked for: Uniformity - check capsules for uniformity in appearance and color. extent of fill - check capsules for uniformity of extent of fill to ensure

that all capsules have been filled. locked - check capsules to ensure that they have all been tightly closed

and locked.

Preparation of Ephedrine Sulfate and Phenobarbital Capsules

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Rx Ephedrine Sulfate 0.025 g. Phenobarbital 0.015 g.

Make 6 capsules Sig.: one cap. q.i.d.

Procedure :

1- The powders are triturated intimately and mixed by geometric dilution .2- The resting powder is placed on a powder paper and smoothed with a

spatula to a height approximately half the length of capsule body.3- The open end of the capsule base is repeatedly pushed into the powder

until the capsule is filled 4- The cap. is then placed back to close the capsule .5- Each filled capsule is weighed using empty capsule as counterpoise,

powder is added or removed until the correct weight is obtained .6- Finally the capsule is cleaned to remove any trace of powder trapped on the

surface

Use : treatment of bronchial asthma .

Calculation:

Calculate for 10 capsules using no. 0 capsules

1. Fill one capsule with lactose in previously described manner and determine the exact capacity of capsule by weighing suppose it is 0.5 g.

2. Calculate the amounts drugs for 10 capsules and substrate from total amount of lactose (0.5 g x 10 ) to get amount of lactose which you will use e.g. ( 0.5 g x 10 – (0.025 x 10 + 0.015 x 10 ) ) = 4.6 g lactose

3. Weigh the calculated amounts of lactose ( 4.6 g ) , ephedrine sulphate (0.25 g ) and phenobarbital ( 0.15 g ) .

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Section (13)

SUPPOSITORIES1-Introduction: Suppositories are medicated, solid bodies of various sizes and shapes suitable for introduction into body cavities. The medicament is incorporated into a base such as cocoa butter which melts at body temperature, or into one such as glycerinated gelatin or PEG which slowly dissolves in the mucous secretions. Suppositories are suited particularly for producing local action, but may also be used to produce a systemic effect or to exert a mechanical effect to facilitate emptying the lower bowel. The ideal suppository base should be nontoxic, nonirritating, inert, compatible with medicaments, and easily formed by compression or molding. It should also dissolve or disintegrate in the presence of mucous secretions or melt at body temperature to allow for the release of the medication. As with the ointment bases, suppository base composition plays an important role in both the rate and extent of release of medications.

2- Methods of preparation :Suppositories can be extemporaneously prepared by one of three methods.

Hand Rolling is the oldest and simplest method of suppository preparation and may be used when only a few suppositories are to be prepared in a cocoa butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-like mass is prepared by triturating grated cocoa butter and active ingredients in a mortar. The mass is formed into a ball in the palm of the hands, then rolled into a uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape.

Effective hand rolling requires considerable practice and skill. The suppository "pipe" or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded and softened.

Compression Molding is a method of preparing suppositories from a mixed mass of grated suppository base and medicaments which is forced into a special compression mold. The method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies and weighing the finished suppositories. When active ingredients are added, it is necessary to omit a portion of the suppository base, based on the density factors of the active ingredients.

72

Fusion Molding involves first melting the suppository base, and then dispersing or dissolving the drug in the melted base. The mixture is removed from the heat and poured into a suppository mold. When the mixture has congealed, the suppositories are removed from the mold. The fusion method can be used with all types of suppositories and must be used with most of them.

3- Suppository bases :Suppository bases may be conveniently classified as according to their composition and physical properties:

Oleaginous (fatty) bases Water soluble or miscible bases (hydrophyllic)

a) Oleaginous Bases include Theobroma Oil and synthetic triglyceride mixtures.

Theobroma Oil or cocoa butter is used as a suppository base because, in large measure, it fulfills the requirements of an ideal base. At ordinary room temperatures of 15° to 25°C (59° to 77°F), it is a hard, amorphous solid, but at 30° to 35°C (86° to 95°F), i.e., at body temperature, it melts to a bland, nonirritating oil. Thus in warm climates, theobroma oil suppositories should be refrigerated.

Particular attention must be given to two factors when preparing suppositories with cocoa butter base. First, this base must not be heated above 35°C (95°F) because cocoa butter is a polymorphic compound and if overheated will convert to a metastable structure that melts in the 25° to 30°C (77° to 86°F) range. Thus, the finished suppositories would melt at room temperature and not be usable. The second factor is the change in melting point caused by adding certain drugs to cocoa butter suppositories. For example, chloral hydrate and phenol tend to lower the melting point. It may be necessary to add spermaceti or beeswax to raise the melting point of finished suppositories back to the desired range.

The newer synthetic triglycerides consist of hydrogenated vegetable oils. Their advantage over cocoa butter is that they do not exhibit polymorphism. They are, however, more expensive. Some of the bases are single entity formulations. Some of the names may denote a series of bases. In a series, the bases are varied to give a range of melting points. For example, Fattibase® is a single entity base that consists of triglycerides

73

from palm, palm kernel, and coconut oils. Wecobee® is a series of bases. Wecobee FS, M, R, and S are all made from triglycerides of coconut oil.

b) Water Soluble/Water Miscible Bases are those containing glycerinated gelatin or the polyethylene glycol (PEG) polymers.

Glycerinated Gelatin is a useful suppository base, particularly for vaginal suppositories. It is suitable for use with a wide range of medicaments including alkaloids, boric acid, and zinc oxide. Glycerinated gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in mucous secretions to provide prolonged release of active ingredients.

Suppositories made with glycerinated gelatin must be kept in well-closed containers in a cool place since they will absorb and dissolve in atmospheric moisture. In addition, those intended for extended shelf-life should have a preservative added, such as methylparaben or propylparaben, or a suitable combination of the two. To facilitate administration, glycerinated gelatin suppositories should be dipped in water just before use.

Calibration of Suppository Molds with Glycerinated Gelatin Base

Glycerinated Gelatin Suppositories have the following proportions of glycerin, gelatin, and water. Use 75 g of the suppository base for this calibration exercise.

IngredientsPercentage

Weight BasisAmt./Vol. to measure

Glycerin 70% __________ g _________ mlGelatin 20% __________ g _________ gPurified Water 10% __________ g _________ ml

To calibrate the mold with glycerinated gelatin suppository base:

Clean mold with soap and water. Dry the mold. Have the mold at room temperature. Lubricate the mold with light mineral oil. Mix the glycerin and water together and heat on a steam bath or hot

plate for 5 minutes. Gently stir in the gelatin to avoid incorporating air in the mixture. After the gelatin has been added, continue heating for

74

another 40 - 50 minutes. Do not allow the temperature to get above 90 - 95°C, as the color will darken.

Remove from the heat and allow the mixture to cool near the melting point before pouring into the mold.

Overfill the cavities in the mold, cool at room temperature for 30 minutes, and then place in a refrigerator 15-20 minutes if the suppositories have not completely congealed.

Carefully remove excess with a hot spatula or knife. Remove suppositories from mold.

Using only perfect specimens, weigh the suppositories and record the total weight. Calculate the average suppository weight.

Mold # __________Total weight for ____ suppositories = _________ gAverage weight for one suppository = _________ gMold lubricant used _____________________Inspection of Final Product _____________________

N.B.- Gelatin base is incompatible with many of the substances prescribed in

supp. E.g. Tannic acid , Ferric chloride , Gallic acid , and for this another reasons this base is less frequently use than coca butter .

- Glycerin supp. Containing Ichthammol became insoluble on storage - Gelatoglycerin bases used mainly for preparing supp. Containing

boric acid , chloral hydrate , ichthamol , iodine (dissolved by the aid of KI )

Standardization of suppositorise : The Standardization of any supp. Involves the following determinations:

a- Determination of DISPLACEMENT VALUE of the active ingredients

b- Determination of FRACTURE POINT of the prepared supp. ( the weight under which the supp. Sample collapses under given conditions is taken as a measure of the strength of the supp. Tested .

c- determination of MELTING TIME of the prepared suppository .

d- determination of UNIFORMITY OF WEIGHT of the prepared suppository .

75

Preparation of the glycerogelatin bases :

- In a prcelin dish soak the gelatin powder with amount of H2O present in the formula for about 5 – 10 min. till it completely wetted and swelled

- add the amount of glycerin to the soaked gelatin.

- Put the dish on boiling water bath .

- Stirr gently till complete solubility of gelatin and the formulation of a translucent mass, avoid air bubbles formation during stirring

- Pour the translucent mass into mould (previusly lubricated with liquid paraffin or any other oil ) after adding the medicament (if the formula containing medicament ) and – Take care that preferably JUST FILL the cavities because the mass does not contract upon cooling .

Preparation of Boroglycerin Suppository

Rx

Boric acid 7.5 gGelatin 15.0 gGlycerin 62.5 g Water 15.0 g

Fiat supp. Mitte III

Calculation :-- The formula gives 100 g of suppository mass.- To prepare 3 supp. Calculate for 5 .- If we use mould of 1 g capacity the amounts are as follows :Boric acid = (1 x 5 x 7.5 ) / 100 = 0.375 gGelatin = ( 1 x 5 x 15 ) / 100 = 0.750 gGlycerin = ( 1 x 5 x 62.5 ) / 100 = 3.125 gWater = ( 1 x 5 x 15 ) / 100 = 0.750 g

-If we use mould of 2 g capacity the amounts given above multiplied by (2) and so on.

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Prepartaion :

- In a porcelin dush soak gelatin in water , then transfer to dish over a water bath .

- Dissolve boric acid in glycerin by the aid of gentle heat .

- Add the dissolved boric acid the gelatin solution and continue heating over a water bath until a clear solution produced and constant wt is attained .

N.B.

- Boric acid reacts with glycerin on heating giving glyceryl borate which has an antiseptic action .

77

78

Section(14)

APPENDEX (A)

Latin Terms and Common Abbreviations

Latin TermCommon

AbbreviationTranslation

a...ad ad to, up to

ad lib. at pleasureadde add add (thou)agita agit shake, stir

alternis horis alt. h. every other hourana a.a. or aa of eachante a. before

ante cibum a.c. before food, before mealsante meridien a.m. morning

amp. ampuleaqua aq. water

aqua ad aq. ad. water up toag. dest; aqua dist. distilled water

auris aur.; a earauris dexter a.d. right earaurix laevus a.l. left earauris sinister a.s. left ear

auris utro a.u. each earauristillae aurist ear-drops

a.t.c. around the clockb...

bis b. twicebis in die b.i.d. twice a daybrachium brach. the arm

BSA body surface areac...

capsula caps a capsulec.c. cubic centimeter

chartulae charts powder papers; divided

79

powderscibus cib.; c. food

collunarium collun a nose washcollutorium collut. a mouthwashcollyrium collyr. an eyewash

compositus comp. compoundcongius cong.; C. gallon

cum c or c. withcum cibus c.c. with food; with meals

d...dentur d. give (thou); let be given

dentur tales doses d.t.d. give of such dosesdexter d. right

diebus alternis dieb. alt. every other daydilutus dil. dilute, diluted

disp. dispensediv. divideDW distilled water

e...elix. elixir

emulsum emuls. emulsionet et and

ex modo prescripto e.m.p.in the manner prescribed; as

directedf...

fac, fiat, fiant f.; ft. let it be made; makef.; fl. fluid

g...g.; G.; gm. gram

granum gr. grainguttae gtt. a drop

h...hora h at the hour of

hora somni h.s. at bedtimei...

i.m. intramuscularinjectio inj. injection

i.v.; IV intravenousi.v.p.; IVP intravenous push

80

IVPB intravenous piggybackj...

k...

l...laevus l. left

linimentum lin. linimentliquor liq. a solution

lot. lotionm...

minimum min; Mx minummisce m.; M mix

mcg. microgrammEq. milliequivalentmg. milligramml. milliliter

n...nocte n. at night

naristillae narist. nasal dropsnebule neb. a spray

N.F. National Formularynon repetatur non.rep. do not repeat

NS normal salineo...

octarius O. pintoculentum occulent. eye ointment

oculus o. eyeoculus dexter o.d. right eyeoculus laevus o.l. left eyeoculus sinister o.s. left eye

oculus utro o.u. both eyes, each eyeomni mane o.m. every morning

p...parti affectae applicandus

p.a.a. to be applied to affected part

per os p.o. by mouthpost cibum p.c. after meals

p.r. per rectum

81

pro re nata p.r.n. as neededpulvis pulv. powder

q...quater in die q.i.d. four times a day

quaque q. each, everyquaque die q.d. every day

quaque hora q.h. every hourquantum sufficiat q.s. a sufficient quantity

quantum sufficiat ad q.s. ad a sufficient quantity to maker...

s...secundum artem s.a. according to the art

S.C.; subc; subq subcutaneouslysemis ss one-halfsigna Sig. write, labelsine s without

si opus sit s.o.s. if necessarysol. solution

statim stat. immediatelysuppositorum supp. suppository

syrupus syr. syrupt...

tabella tab. tablettbsp. tablespoonful

ter in die t.i.d. three times a day

tinc.; tr. tincture

trochiscus troche lozenge

tussis tuss. a cough

u...ungentum ung. an ointment

ut dictum ut dict.; u.d. as directed

82