international by: prof. dr. anayanti arianto, apt. prof...

PRACTICAL

MANUAL

STERILE

DOSAGE FORM

TECHNOLOGY

Laboratory of Pharmaceutical

Dosage Form Technology

Fakulty of Pharmacy

University of Sumatera Utara

2019

INTERNATIONAL

CLASS

BY:

Prof. Dr.

Anayanti Arianto,

Apt.

Prof. Dr. Julia

Reveny, M.Si.,

Apt.

Prof. Dr.

Wiryanto, M.S.,

Apt.

Dra. Nazliniwaty,

M.Si., Apt.

Lia Laila,

S.Farm., M.Sc.,

Apt.

i

PRACTICAL MANUAL

STERILE DOSAGE FORM TECHNOLOGY

NAME :

STUDENT No. :

GROUP :

PROGRAMME : SI - INTERNATIONAL

By :

Prof. Dr. Anayanti Arianto, M.Si., Apt

Prof. Dr. Wiryanto, M.Si., Apt

Prof. Dr. Julia Reveny, M.Si., Apt

Dra. Nazliniwaty, M.Si., Apt

Lia Laila, S.Farm., M.Sc., Apt

LABORATORY OF PHARMACEUTICAL DOSAGE FORM TECHNOLOGY

FACULTY OF PHARMACY

UNIVERSITY OF SUMATERA UTARA

2019

ii

FOREWORD

Manual drug compounding period based on the hand skill which previously performed in drug

store had been passed a long time ago. It changes to technology and automatic production

machines period in pharmaceutical industry. Drug manufacture is no longer as simple as

compounding because pharmaceutical industry has to follow the steps and regulation based on

Good Manufacturing Practice (GMP) which include all the production and quality control

aspects. Following the changes in pharmaceutical industry, Sterile Dosage Form Laboratory

with available facility take effort to design continuosly the learning process, training and topic

in practical class based on the drug supply which become society need and requirement.

This practical manual is intended to be a guidance for students to conduct the Sterile Dosage

Form Practical Class. This practical manual is an excercise to plan and perform the Standard

Operational Procedure of sterilization and also excercise to plan and perform sterile product

manufacturing based on GMP procedure. It is expected that students will have competent

knowledge level, certain skill and ability in sterile product manufacturing.

Hopefully this practical manual can assist students to do practice, therefore the result can be

achieved according to the purpose.

Medan, February 2019

Laboratory of Pharmaceutical Dosage

Form Technology

Faculty of Pharmacy

University of Sumatera Utara

iii

TABLE OF CONTENT

Cover ........................................................................................................................ i

Forewords ............................................................................................................... ii

Table of Content ..................................................................................................... iii

Rule of the laboratory........……………………………………………………..... iv

Tools SOP .............................................................................................................. v

Practical I : Production and Packaging of Large Volume Single

Dose Injection .................……………………………... 1

Practical II : Production And Packaging Of Small Volume Single

Dose Injection (Ampoule)..........………………………..... 15

Practical III : Production And Packaging Of Small Volume Multiple

Doses Injection (Vial)………........................................... 29

Practical IV : Production And Packaging Of Eye

Drop Product ………………………..................…….… 43

Practical V : Production And Packaging Of Eye

Ointment Product …………………….......................….. 56

Practical VI : Evaluation Of Sterile Products............……………....…… 69

iv

PRACTICAL REQUIREMENTS

AND

RULE OF THE LABORATORY

Practical Requirements

1. Students that can take practical class should have finished the Sterile Dosage Form

course.

2. For every meeting, each student has to attend the Drug Manufacturing Plan discussion

which is prepared in the Main Manufacturing Procedure and Main Packaging

Procedure.

3. After finish each practical class, student is required to make written report as

Manufacturing Documents which is included: Main Manufacturing Procedure and

Batch Manufacturing Record. The reports are given before attend the Drug

Manufacturing Plan discussion for the next practical title.

4. Students that do not attend the plan discussion and do not hand over the practical

report will not be allowed to follow the next practical class.

5. The final marking (practical evaluation) is in the form of examination to make Main

Manufacturing Procedure.

Rule of the Laboratory

1. Attend 1 hour before practical class begin.

2. Wear suitable clothes according to the Faculty of Pharmacy requirements.

3. Wear laboratory coat with long sleeve, head cover, masker, and gloves.

4. Do not wear jewelry, accessories, or other source of contaminant during the practical

class..

5. It is not allowed to eat, drink, smoking and talking in the laboratory.

6. The required tools can be obtained from the laboratory using a tools record.

7. Before practical start, the tools have to be cleaned and wrapped, ready to be sterilized.

8. Broken glasswares, damage or missing tools should be replaced as soon as possible.

9. Prepare 2 piece of clean clothes, wool, glue, small scissor, and secondary packaging

include label and brochure for the related products.

10. Keep silent and keep clean during the practical class.

v

STANDARD OPERATING PROCEDURE FOR STERILIZATION

OF TOOLS AND CONTAINERS

No. Tools/Materials Sterilization

method

Temperature and

Time

Sterilization

time

1 Beaker glass Oven 170°C 30 min

2 Erlenmeyer Oven 170°C 30 min

3 Measuring cylinder Oven 170°C 30 min

4 Watch glass Oven 170°C 30 min

5 Glass rod Oven 170°C 30 min

6 Funnel + filter paper Autoklaf 121°C 15 min

7 Vial + aluminium

closure Oven 170°C 30 min

8 Bottle + aluminium

closure Oven 170°C 30 min

9 Rubber closure Autoklaf 121°C 15 min

10 Ampoule Oven 170°C 30 min

11 Tube + closure Autoklaf 121°C 15 min

12 Eye drop bottle Autoklaf 121°C 15 miin

13 Mortar and stamfer Oven 170°C 30 min

14 Sudip Autoklaf 121°C 15 min

15 Spatula Oven 170°C 30 min

16 Distilled water Autoklaf 121°C 15 min

1. Tools or containers are cleaned.

2. Tools and container are wrapped with paper.

3. Wrapped tools or containers are placed in to the sterilization apparatus according to the

table, count the sterilization time starting from the required temperature.

4. After the sterilization process is finished, turn off the apparatus, take out the sterilized

tools or container.

Practical Manual of Sterile Dosage Form Technology 1

PRACTICAL I

I. TOPIC : PRODUCTION AND PACKAGING OF LARGE VOLUME

SINGLE DOSE INJECTION

II. AIM : to produce, pack and sterilize large volume single dose injection

III. R/

IV. THEORY

An injection is a preparation intended for parenteral administration and/or for

constituting or diluting a parenteral article prior to administration. It is administered

through the skin or other external boundary tissue, rather than through the alimentary

canal, so that therapeutic substances, using gravity or force, can gain direct entry to a

blood vessel, organ, tissue, or lesion.

The USP categorizes sterile preparations for parenteral use according to the physical

state of the product as follows:

1. Liquid preparations that are drug substances or solutions thereof, for example,

[drug] injection.

2. Dry solids that, upon the addition of suitable vehicles, yield solutions conforming

in all respects to the requirements for injections, for example, [drug] for injection.

3. Liquid preparations of drug substances dissolved or dispersed in a suitable

emulsion medium, for example, [drug] injectable emulsion.

4. Liquid preparations of solids suspended in a suitable liquid medium, for example,

[drug] injectable suspension.

5. Dry solids that, upon the addition of suitable vehicles, yield preparations

conforming in all respects to the requirements for injectable suspensions, for

example, [drug] for injectable suspension.

Depending on the volume of injection in a package, the USP further designates

injection, as either


(i) Small-volume injections or

(ii) Large-volume intravenous (IV) solutions.

The term small-volume injection applies to an injection that is packaged in

containers labelled as containing 100 mL or less. The large-volume IV solution

applies to a single-dose injection that is intended for IV use and is packaged in

containers labelled as containing more than 100 mL.

The term sterilization, as applied to pharmaceutical preparations, means destruction

of all living organisms and their spores or their complete removal from the

preparation. Five general methods are used to sterilize pharmaceutical products:

1. Steam

2. Dry heat

3. Filtration

4. Gas

5. Ionizing radiation

In every container, the volume of injection should excess the volume stated on the

label to fulfil the uniformity of volume. The suggested additional volumes are listed

in Table 1.

Table 1. Suggested additional volume

Volume stated in label Additional volume

Non viscous liquid (ml) Viscous liquid (ml)

0,5 ml

1,0 ml

2,0 ml

5,0 ml

10,0 ml

20,0 ml

30,0 ml

50,0 ml or more

0,10

0,10

0,15

0,30

0,50

0,60

0,80

2 %

0,12

0,15

0,25

0,50

0,70

0,90

1,20

3%


V. PREPARATION

a. Ingredients

b. Vehicle

c. Container (primary packaging)

d. Tools


e. Materials

f. Calculation

1. Number of products that will be produced

2. Amount of materials that are needed

No. Name of tools Number Sterilization method Signature


3. Tonicity calculation


VI. PRODUCTION

Procedure:

VII. PACKAGING

a. Where does the packaging process take place? Give the reason.


b. Write down the Label/Brochure needed for the product


VIII. REFERENCES

------------------------------------------------------------------------------------------------------------

Questions

1. Why do the large volume injections should be pyrogen free?

2. What is the function of carbon absorbent addition in the production of large

volume injection products?


MAIN PRODUCTION PROCEDURE

BATCH PRODUCTION RECORD

Name of company : …………………

Procedure/Record No. : …………………

Product

Code:

Name of

Product:

Batch

No.:

Bacth

volume:

Type:

Container:

Date :

Start time :

Finish time:

I. Ingredients :

Volume of 1 batch = .............. containing :

II. Specification

A. Description :

B. Materials :

C. Primary container


III. Weighing

No

.

Name of

material

Amount needed Amount weighted Signature

IV. Tools

No. Name of tool Sterilization method Signature


V. Production

Procedure Signature

1

2

3

4

5

6

. . . . .. .

. . . . . .

. . . .. . .

. . . . . .

. . .. . . .

. . .. . . .

VI. Filling

VII. Sterilization

VIII. Reconciliation

Reconciliation Checked by : Approved by :

Theoretical result :

Real result :

Deviation : %

Result range l : 97,0-100,5%

Production Supervisor

Date :

Production Manager

Date:


MAIN PACKAGING PROCEDURE

BATCH PACKAGING RECORD



Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:

Packaging and Labelling

1. Labelling on the primary container

2. Labelling on the box


3. Brochure preparation


4. Final packaging :

� Pack the labelled bottle with brochure in to wrapped box.

� Pack the filled wrapped box in to Master Box

� Label Master Box with outside label

� Label with QUARANTINE

� Theoretical result :

� Real result :

� % from theoretical result :

� Result range 99,5 – 100% from theoretical result

� If the real result is out of the range, do “failure investigation” and give

explanation below

� Explanation :


PRACTICAL II

I. TOPIC : PRODUCTION AND PACKAGING OF SMALL VOLUME

SINGLE DOSE INJECTION (AMPOULE)

II. AIM : to produce, pack and sterilize small volume single dose injection

III. R/

IV. THEORY









[drug] injection.












(i) small-volume injections or


(ii) large-volume intravenous (IV) solutions.

Generally, injection products are produced to be given by venous (intra-venous;IV),

muscle (intra-muscular;IM), dermal (intra-dermal;ID), or under the skin

(subcutaneous; SC). However, a lot of products are injected through specific organ

such as heart, artery, ocular and so on.

In the injections manufacturing, the suitable excipients can be added to increase

stability or activity, except it is stated in each monograph. Additional excipients

should not be dangerous in the used amount and should not affect the therapeutic nor

respond to the test and assay. The excipients are included vehicle, solubilizing agent,

buffer, preservatives, anti-oxidants, inert gas, surfactants, complexion and chelating

agents.

To protect easily oxidized drugs, then it is recommended to add an anti-oxidant to

maintain the drug stability. Some of anti-oxidants that can be used as excipients in

injectable drug are listed in Table 2.

Table 2. Anti-oxidants used as injectable drug excipients

Anti-oxidant Used concentration (%)

Ascorbic acid

Butyl hydroxyanisole

Cystein

Monothioglycerol

Sodium bisulphite

Sodium metabisulphite

Thiourea

Tocopherol

0.01- 0.5

0.005 – 0.02

0.1- 0.5

0.1 – 1.0

0.1 – 1.0

0.1 – 1.0

0.005

0.05 – 0.5

V. PREPARATION

a. Ingredients


b. Vehicle


d. Tools



e. Materials

f. Calculation





VI. PRODUCTION

Procedure:

VII. PACKAGING

a. Where does the packaging process take place? give the reason.


VIII. REFERENCES

------------------------------------------------------------------------------------------------------------

Questions

1. Give another method of sterilization for small volume injectable drug in

ampoule.

2. How to produce air free water for injection?






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:

I. Ingredients :

Volume of 1 batch = .............. containing:

II. Specification

A. Description :

B. Materials :



III. Weighing

No

.

Name of

material


IV. Tools



V. Production

Procedure Signature

1

2

3

4

5

6

. . . . .. .

. . . . . .

. . . .. . .

. . . . . .

. . .. . . .

. . .. . . .

VI. Filling

VII. Sterilization




Real result :

Deviation : %



Date :

Production Manager

Date:






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:











� Real result :




explanation below

� Explanation :


PRACTICAL III

I. TOPIC : PRODUCTION AND PACKAGING OF SMALL VOLUME

MULTIPLE DOSES INJECTION (VIAL)

II. AIM : to produce, pack and sterilize small volume multiple doses injection

III. R/

IV. THEORY









[drug] injection.












(iii) small-volume injections or


(iv) large-volume intravenous (IV) solutions.

Parenteral dosage form can be packed in single or multiple doses. Product packed in

multiple dose containers such as vial should contains preservative to prevent the

growth of microorganisms which probably enter in to the container when it is used.

However, there is a limitation of preservatives which not all of them compatible with

the active drug. As example, benzyl alcohol is not compatible with sodium succinate

chloramphenicol and paraben group and phenol are not compatible with

nitrofuranthoin, amphotericin B and erytromycin. It is very important to choose

suitable preservative that compatible with the active drug. The preservatives also

should be compatible with the container and the closure of the product.

Some of preservatives in parenteral product are listed in Table 3.

Preservatives Used concentration (%)

Benzalkonium chloride

Benzethonium chloride

Benzyl alcohol

Chlorobutanol

Chlorocresol

Cresol

Metacresol

Ester of p-hidroxy benzoate:

Butyl

Methyl

Propyl

Thimerosal

0,01

0,01

1,0 – 2,0

0,25 – 0,5

0,1 – 0,3

0,3 – 0,5

0,1 – 0,3

0,015

0,1 – 0,2

0,02 – 0,2

0,01


V. PREPARATION

a. Ingredients

b. Vehicle


d. Tools


e. Materials

f. Calculation




VI. PRODUCTION

Procedure:

VII. PACKAGING



VIII. REFERENCES

------------------------------------------------------------------------------------------------------------

Questions

1. What is the function of preservative in the production of multiple dose

injection in vial?






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:

I. Ingredients :


II. Specification

A. Description :

B. Materials :



III. Weighing

No

.

Name of

material


IV. Tools



V. Production

Procedure Signature

1

2

3

4

5

6

. . . . .. .

. . . . . .

. . . .. . .

. . . . . .

. . .. . . .

. . .. . . .

VI. Filling

VII. Sterilization




Real result :

Deviation : %



Date :

Production Manager

Date:






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:











� Real result :




explanation below

� Explanation :


PRACTICAL IV

I. TOPIC : PRODUCTION AND PACKAGING OF EYE DROP

PRODUCT

II. AIM : to produce, pack and sterilize eye drop product

III. R/

IV. THEORY

Eye drop product or Guttae Opthalmicae is a sterile dosage form in solution

or suspension, used to the eye by drop the drug solution in the conjunctive

layer around the eye lid and eye ball.

Eye drops are used to treat allergy, infections due to bacteria or virus,

glaucoma, and other eye disease. Eye is continuously exposed to the air, dirt,

pollutant, allergen, bacteria and other foreign material, when the protection

mechanism is occurred, then it is required eye product in the form of solution,

suspension or ointment.

In eye drop solution manufacturing, the physicochemical characteristic

should be considered, include: clarity, tonicity, pH, and sterility. For

suspension form, particle size in the product should be small enough which

will not irritate or scratch the cornea of the eye.

The usage of excipients such as preservatives, anti-oxidant and to increase

viscosity should be carefully considered. Eye drop solution usually is

buffered in pH where the maximum stability of the contained active drug can

be achieved.


V. PREPARATION

a. Ingredients

b. Vehicle


d. Tools


e. Materials



f. Calculation





VI. PRODUCTION

Procedure:

VII. PACKAGING

a. Where does the packaging process take place? Give the reason.


VIII. REFERENCES

------------------------------------------------------------------------------------------------------------

Questions

a. What is the function of preservatives addition in the manufacturing of eye

drop product?

b. How to select suitable preservatives for eye drop product?

c. Give another method of sterilization that can be done to produce eye drop

product.






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:

I. Ingredients :


II. Specification

A. Description :

B. Materials :



III. Weighing

No

.

Name of

material


IV. Tools



V. Production

Procedure Signature

1

2

3

4

5

6

. . . . .. .

. . . . . .

. . . .. . .

. . . . . .

. . .. . . .

. . .. . . .

VI. Filling

VII. Sterilization




Real result :

Deviation : %

Result range : 97,0-100,5%


Date :

Production Manager

Date:






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:











� Real result :




explanation below

� Explanation :


PRACTICAL V

I. TOPIC : PRODUCTION AND PACKAGING OF EYE OINTMENT

PRODUCT

II. AIM : to produce, pack and sterilize eye ointment product

III. R/

IV. THEORY

Eye ointment is a sterile ointment for eye treatment purpose using suitable ointment

base. It is different with the dermatological ointment, eye ointment should be sterile.

Eye ointment should fulfil the sterility test as states in the official compendia.

Therefore, eye ointment can be defined as semi solid dosage form which easily

applies for topical usage on skin or mucous membrane in the eye where the active

drug should be soluble or dispersed homogenise in the suitable ointment base.

Based on Pharmacopoeia, ointment base used as vehicle is divided in to 4 groups:

1. Hydrocarbon ointment base

2. Absorbed ointment base

3. Washable ointment base

4. Water soluble ointment base

The selection of ointment base is depended on several factors such as the desired

effect, physicochemical properties of the drug, bioavailability and stability of the

product.


V. PREPARATION

a. Ingredients

b. Vehicle


d. Tools


e. Materials



f. Calculation




VI. PRODUCTION

Procedure:

VII. PACKAGING



VIII. REFERENCES

------------------------------------------------------------------------------------------------------------

Questions

1. Give example of other ointment base according to the Martindale Extra

Pharmacopoeia.

2. Give another eye ointment available in the market which contain same active

ingredient with your product.

3. Why does this eye ointment do not require addition of preservative?






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:

I. Ingredients :


II. Specification

A. Description :

B. Materials :



III. Weighing

No

.

Name of

material


IV. Tools



V. Production

Procedure Signature

1

2

3

4

5

6

. . . . .. .

. . . . . .

. . . .. . .

. . . . . .

. . .. . . .

. . .. . . .

VII. Filling

VIII. Sterilization

IX. Reconciliation



Real result :

Deviation : %

Result range : 97,0-100,5%


Date :

Production Manager

Date:






Product

Code:

Name of

Product:

Batch

No.:

Batch

volume:

Type:

Container:

Date :

Start time :

Finish time:











� Real result :




explanation below

� Explanation :


PRACTICAL VI

I. TOPIC: EVALUATION OF STERILE PRODUCTS

II. AIM: To evaluate injection products, eye drop product and eye ointment

products.

III. EVALUATIONS OF STERILE PRODUCTS

1. Sterility Test

Based on Indonesian Pharmacopoeia, there are two methods that can be used to

test the sterility of sterile product:

a. Direct inoculation to culture medium

This evaluation include direct test of sample in growth media. The media

that can be used to perform this test such as liquid thioglycolate medium

(for aerob condition), alternative liquid thioglycolate medium (for anaerob

condition) and soybean-casein digest medium (for bacteria and fungus at

aerob condition).

Procedure:

1. Transfer the liquid from the container using sterile pipette or needle. .

2. Aseptically inoculate certain amount of the sample to the medium

flask.

3. Mix the sample with the medium without excess aeration.

4. Incubate the medium at least for 14 days

5. Observe the growth on the medium regularly during the incubation

period.

b. Membrane filtration

This method include liquid filtration trough sterile membrane by aseptic

technique, then the membrane is placed in the media and incubated for 7-14

days.

2. Pyrogenicity test

The pyrogenicity tests include:

a. Rabbit test


Based on the temperature elevation (fever respond) on rabbit. .

b. LAL (Limulus amebocyte lysate) test

Based on the gel formation of amebocyte lysate originated form

Limulus polyphemus.

Tools and Materials:

- Pyrogen free syringe

- Pyrogen-free needles

- Pyrogen-free test tubes or vials

- Tube rack

- Incubator or oven

- Vortex tool

- LAL reagent

- Test sample or solution

- Universal indicator paper

Procedure:

a. Sample preparation

- All tools and materials used must be free of pyrogen.

- Use aseptic techniques during the experiment

- Test samples must be stored in the refrigerator at a temperature of 2-8 jamC

24 hours before use but must be frozen if not used in 24 hours.

- Test samples must have a pH range of 6-8. Test with universal indicator

paper.

b. Preparation of reagents

Limulus Amebocyte Lysate (LAL)

- Reconstitute lysate powder by adding 2 ml. Reagent water into the vial.

- Stir slowly for at least 30 seconds to dissolve the lysate powder. Do not shake

or vortex to avoid forming foam.

The reconstituted Lisate can be stored at -20˚C or below it for up to 1 week if

it is frozen immediately after reconstitution. Avoid repeated freezing and

search cycles.


c. E. coli Endotoxin Standard

- Reconstitute the E.coli endotoxin standard to a concentration of 0.5 EU / ml

by adding 1 ml of LAL Reagent Water to the vial.

- Mix homogeneously at least 15 minutes with the vortex to obtain endotoxin

mother solution as a positive control.

- Standard endotoxin solutions can be stored at -20˚C or below for up to 15

days.

d. Test procedure

Each experiment must have positive control and negative control. LAL reagent

water can be used as a negative control.

1. Pipette 3 x 0.1 ml of LAL reagent each into a vial or pyrogen-free test tube.

Label or mark as negative controls, positive controls and samples.

2. Carefully add 0.1 ml of negative control solution, positive control and

sample into each vial or test tube that has been labeled above. Close the vial or

test tube and mix it homogeneously.

3. Place the entire vial or test tube into the tube rack to be incubated at 37˚ ±

1˚C in an oven or incubator for 1 hour.

4. After 1 hour, carefully remove the vial or test tube, turning each tube slowly

180˚. Check whether gel is formed or not.

a. A positive reaction if the gel is hard and does not move when the vial or tube

is reversed.

b. A negative reaction if no gel is formed also if there is only turbidity and

thick liquid

3. Visual evaluation

a. Clarity and colour

The product should be clear (no turbidity) and colourless, there is no

undissolved particle in the product.

b. Free of foreign material

The product should be free of foreign materials such as fibre or

undissolved drug material.


The procedure to check the foreign material in the injection product based on the

Good Manufacturing Practice (GMP):

1. Take container with cleaned surface, then hold the neck of the bottle and

slowly reverse the bottle to avoid bubble occurrence. After that, twirl the

bottle slowly to swirl the liquid inside.

2. The container is held horizontally approximately 10 cm under the source

of light. Check the liquid in the container at the black and white

background.

3. If the magnifying glass is used (3x), the container is held at the back of

the magnifying glass at the focus distance approximately 9 cm in front of

the black and white background.

4. The liquid in the container should be free from the presence of particle,

fibre, etc.

5. The container is checked for the physically damage (e.g: broken or

crack).

4. Volume uniformity test (Indonesian Pharmacopoeia, Second Edition)

Procedure:

- Take one or more container if the volume equal to or more than 10 ml, 3

containers or more if the volume more than 3 ml and less than 10 ml, 5

containers or more if the volume equal to or less than 3 ml.

- For the volume less than 10 ml, take the content of each of the container with

hypodermal syringe with capacity not more than 3 times of the measured

volume, connected with gauge no.21 with the length of needle not less than

2.5 cm.

- Remove air bubble from the syringe and needle; release the content of the

syringe without emptying the needle to the calibrated measuring cylinder.

- The content of injection product with volume 1 or 2 ml can be combined in

the same measuring cylinder but it is taken from the container with different

syringe.

- For the volume equal and more than 10 ml, the liquid can be directly poured

to the measuring cylinder.


- The injection volume should be not less than the volume stated on the label,

for the combined volume measurement then the injection volume should be

not less than the total volume of each volume stated on the label.

- For injection in multiple dose container which on the label is stated certain

amount of dose with certain volume, then the test is conducted using the

same procedure by using the same syringe number with the stated amount of

dose. Measured volume should not be less than the all dose volume.

5. pH evaluation

pH evaluation can be tested by:

� pH indicator paper

Paper is immersed in to the liquid of sample. The resulted colour is

compared to the standard colour of pH.

� pH meter

pH value is a value given by the suitable potentiometric device (pH

meter) which had been standardized with the standard buffer liquid. The

standard buffer should has the same condition with the solvent of the

product.

6. Minimum fill

This evaluation is conducted specifically for eye ointment.

Procedure:

a. Take sample as much as 10 containers which contain active

ingredient.

b. Remove all the labels that can affect the weight

c. Clean and dry the outside part of container with suitable method and

weigh one by one

d. Remove the content quantitatively from each container.

e. Cut the edge of the container, wash with suitable solvent if necessary

(be careful of the closure and other part of the container)

f. Dry and weigh each empty container with all the parts.

g. The difference between the weight is the net weight of the content.


h. The average of the net weights from 10 samples should not be less

that the weight stated on the label and none of the sample that the net

weight is less than 90% of the weight stated on label.

7. Label evaluation

The following requirements should be stated on the label of the product:

- Name of product

- Name of ingredients, amount, dose and concentration

- Exp. date

- Administration instruction

- Storage condition

- For infussion: the amount of ions in mEq per litre

- Other required information


EVALUATION PROCEDURE

BATCH EVALUATION RECORD

Name of Company : ......................................

Procedure/Record No. : ......................................

Specification

1. Organoleptic

Type of dosage form/

Name of Product

Batch No. Colour Odor Sign

Infussion/Anticoagulant

Vial

Ampoule

Eye drop

Eye ointment

2. pH


Name of Product

Batch No. Theoretical

pH

Product pH Sign


1.

2.

Vial

1.

2.

Ampoule

1.


2.

Eye drop

1.

2.

3. Volume uniformity


Name of Product

Batch No. Volume

stated on

label

Volume

obtained

Sign


1.

2.

Vial

1.

2.

Ampoule

1.

2.

3.

4.

5.

Eye drop

1.

2.

4. Clarity/ foreign material


Name of Product

Batch No. Clarity Foreign

material

Sign


1.

2.


Vial

1.

2.

Ampoule

1.

2.

Eye drop

1.

2.

5. Minimum fill

No. Type of dosage form/

Name of Product

Batch No. Net Weight

obtained (g)

Sign

Average weight

Weight stated on the label (g)

Calculation:

Net weight = The weight of content and container – empty container


6. Labelling


Name of Product

Batch No. Label Signature


Vial

Ampoule

Eye drop

Eye ointment

Reconciliation

Reconciliation Checked by : Approved by:

Conclusion:

Supervisor

Date :

Quality Control

Manager

Date:


Notes: