powders,modified, lec 8

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Advantages of powders:Advantages of powders:

• Good chemical stability compared with fluidsGood chemical stability compared with fluids• useful for bulky drugs with large dose, e.g. useful for bulky drugs with large dose, e.g.

indigestion powder. indigestion powder. • Easy to swallow even in large bulk, especially if Easy to swallow even in large bulk, especially if

mixed with drink food (useful for stomach- tube mixed with drink food (useful for stomach- tube feeding)feeding)

• The smaller particle size of powders causes The smaller particle size of powders causes more rapid dissolution in body fluids, increases more rapid dissolution in body fluids, increases drug bioavailability, and decreases gastric drug bioavailability, and decreases gastric irritation compared with tablets irritation compared with tablets

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Disadvantages of PowdersDisadvantages of Powders• Not suitable for drugs unstable in Not suitable for drugs unstable in

atmospheric conditions atmospheric conditions • Not suitable for bitter, nauseating, Not suitable for bitter, nauseating,

deliquesnt and corrosive drugs.deliquesnt and corrosive drugs.• Inaccuracy of dose in case of bulk Inaccuracy of dose in case of bulk

powderpowder• Inconvenient to carry.Inconvenient to carry.

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Types of PowdersTypes of Powders1- 1- Divided powdersDivided powders

- packets- packets- cachets - cachets - capsules- capsules

2- 2- Undivided (Bulk) powdersUndivided (Bulk) powders- dusting powder - dusting powder - effervescent powder- effervescent powder- antacids, laxatives, dietary - antacids, laxatives, dietary nutrient supplements….nutrient supplements….

http://www.inmagine.com/cr15205/cr15205036-photo

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• Oral divided powderOral divided powder may contain one or may contain one or more active ingredients together with an more active ingredients together with an inert diluent to produce a minimum inert diluent to produce a minimum quantity of 120 mg.quantity of 120 mg.

• Oral undivided powderOral undivided powder are usually a are usually a simple mixture of the prescribed simple mixture of the prescribed medication without additional medication without additional ingredients. ingredients.

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Preparation of powdersPreparation of powders1- Reduction of particle size of all 1- Reduction of particle size of all

ingredients to the same range to ingredients to the same range to prevent stratification.prevent stratification.

2- Sieving.2- Sieving.3- Weighing of each ingredient.3- Weighing of each ingredient.4- Mixing.4- Mixing.5- Packaging.5- Packaging.

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• Example of undivided oral powder:Example of undivided oral powder:

prepare 100 gram Compound magnesium prepare 100 gram Compound magnesium Trisilicate Oral Powder BP 1988.Trisilicate Oral Powder BP 1988.ingredientsingredients amountamountmagnesium trisilicatemagnesium trisilicate 250 g250 gchalk, in powderchalk, in powder 250 g250 gsodium bicarbonatesodium bicarbonate 250 g250 gheavy magnesium carbonateheavy magnesium carbonate 250 g250 g

Action and Use: Adsorbent and antacid for Action and Use: Adsorbent and antacid for treatment of dyspepsia.treatment of dyspepsia.

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Example of divided oral powder:Example of divided oral powder:

• Prepare Oral Rehydrated Salts BP 1988Prepare Oral Rehydrated Salts BP 1988• IngredientIngredient amount to prepare 1 litre amount to prepare 1 litre

solutionsolutionSodium chlorideSodium chloride 1.0 g1.0 gPotassium chloridePotassium chloride 1.5 g1.5 gSodium bicarbonateSodium bicarbonate 1.5 g1.5 gAnhydrous glucoseAnhydrous glucose 36.4 g36.4 g

• Action and use: Rehydration and electrolyte replacement Action and use: Rehydration and electrolyte replacement in treatment of diarrhea.in treatment of diarrhea.

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Methods of Powder MixingMethods of Powder Mixing

1- Mechanical Mixing1- Mechanical Mixing2- Hand Mixing:2- Hand Mixing:

2.1- Spatulation (spatula + tile)2.1- Spatulation (spatula + tile)2.2- Trituration (mortar + pestle)2.2- Trituration (mortar + pestle)2.3- Tumbling (wide mouth closed 2.3- Tumbling (wide mouth closed container)container)

Geometric dilution: Geometric dilution: Entire quantity of potent drug (x volume) + (x volume) of the diluents + (2x volume) of the diluents + (4x volume) of the diluents………repeated until all the diluents are used.

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Problems encountered in Problems encountered in powder formulationpowder formulation1-1- Hygroscopic and Deliquescent Hygroscopic and Deliquescent

PowderPowderProblem:Problem: Absorption of moisture from air Absorption of moisture from air leading to partial or complete liquefaction.leading to partial or complete liquefaction.Solution:Solution: A-A- Applied in a granular form to Applied in a granular form to decrease the exposed surface to air.decrease the exposed surface to air.B-B- Packed in aluminum foil or in plastic film Packed in aluminum foil or in plastic film packetspacketsC-C- Addition of light magnesium oxide to reduce Addition of light magnesium oxide to reduce the tendency to dampthe tendency to dampD-D- Addition of adsorbent materials such as Addition of adsorbent materials such as starchstarchExamples:Examples: - halide salts (ex. Sod. Iodide) - halide salts (ex. Sod. Iodide)- Certain alkaloids (physostigmine Hcl)- Certain alkaloids (physostigmine Hcl)

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Problems encountered in Problems encountered in powder formulationpowder formulation

2- Efflorescent powders2- Efflorescent powdersProblem:Problem: Crystalline substances which Crystalline substances which

during storage loose their water of during storage loose their water of crystallization and change to powder crystallization and change to powder (to be efflorescent). The liberated (to be efflorescent). The liberated water convert the powder to a paste water convert the powder to a paste or to a liquid.or to a liquid.

Examples:Examples: Alum- atropine sulfate- Alum- atropine sulfate- citric acid- codeine phosphate…citric acid- codeine phosphate…

Solution:Solution: Using the anhydrous form, Using the anhydrous form, and treating it in a manner similar to and treating it in a manner similar to hygroscopic powdershygroscopic powders

http://en.wikipedia.org/wiki/Image:Alum.jpg

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Problems encountered in Problems encountered in powder formulationpowder formulation3- Eutectic Mixtures3- Eutectic MixturesProblem:Problem: mixture of substances that liquefy when mixture of substances that liquefy when

mixed, rubbed or triturated together. The mixed, rubbed or triturated together. The melting points of many eutectic mixtures are melting points of many eutectic mixtures are below room temperature. below room temperature.

Examples:Examples: menthol- thymol- phenol- salol- menthol- thymol- phenol- salol- camphor…….camphor…….

Solution:Solution: A A- using inert adsorbent such as starch, - using inert adsorbent such as starch, talc, lactose to prevent dampness of the powdertalc, lactose to prevent dampness of the powderB-B- dispensing the components of the eutectic dispensing the components of the eutectic mixture separately.mixture separately.

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Problems encountered in Problems encountered in powder formulationpowder formulation4- Incorporation of Liquids4- Incorporation of LiquidsSolution:

A- The liquid is triturated with an equal weight of the powder and the remaining powder is added in several portions with trituration. B- Adsorbent is incorporated, usually light kaolin.

15Problems encountered in Problems encountered in powder formulationpowder formulation5- Incorporation of Extracts5- Incorporation of ExtractsProblem: Some plant extracts are available as

powders or as semisolid (e.g., liquid extract of liquorice) .

Solution: A- The powdered extracts have no problems and

treated generally as powdersB- Semisolid extract should be mixed with an equal

quantity of lactose and reduced to a dry powder by evaporation before incorporation with other ingredients

C- Careful heating, if present, to save potency of the extract.

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Problems encountered in Problems encountered in powder formulationpowder formulation

6- Potent Drug6- Potent DrugProblem: Limited precision and accuracy of the

used balances to weight small amounts of potent drugs.

Solution: Drug triturates:A- Suitable diluents like lactose are mixed with the potent drug to form 10 - 20%w/w drug triturates. B- Very fine powders should be used in the trituratesC- Geometric dilution to prepare drug triturates

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• Example:Example:Send 3 powders each containing 8 mg propranolol Send 3 powders each containing 8 mg propranolol hydrochloride for a child weighing 8 kghydrochloride for a child weighing 8 kg one powderone powder four powders four powdersPropranolol hydrochloridePropranolol hydrochloride 8 mg8 mg 32 mg32 mgLactoseLactose 112 mg112 mg 448 mg448 mg

• TotalTotal 120 mg120 mg 480 mg480 mg• Trituration:Trituration:

propranolol hydrochloridepropranolol hydrochloride 100 mg100 mglactoselactose400400So, each 100 mg of triturate contains 20 mg drug and So, each 100 mg of triturate contains 20 mg drug and therefore 160 mg of triturate will contain 32 mgtherefore 160 mg of triturate will contain 32 mg

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Problems encountered in Problems encountered in powder formulationpowder formulation7- Incompatible salts7- Incompatible saltsProblem: Chemically incompatible salts when triturated

together produce discoloration, chemical deterioration or loss of potency.

Solution: A- Compounding such substances with minimum pressure B- Use a convenient method for mixing the powder like tumbling in a jar or spatulation on a sheet of paper.C- Each substance should be powdered separately in a clean mortar and then combined with other ingredients gently.D- Powder and dispense separately.

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Problems encountered in Problems encountered in powder formulationpowder formulation8- Explosive mixtures8- Explosive mixturesProblem: Oxidizing agents(ex. Pot. Salts of

chlorate, dichromate, permanganate and nitrate- Sod. Peroxide- silver nitrate and silver oxide) explore violently when triturated in a mortar with a reducing agent ( ex. sulfides- sulfur- tannic acid- charcoal).

Solution: A- Comminute each salt separately. B- Subject to a minimum pressure.

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Special PowdersSpecial Powders1- Effervescent Powders1- Effervescent Powders

• Definition: Mixture of organic acid and alkali effervesces when subjected to water due to reaction between the acid and the base with evolution of co2

• Examples: Citric or tartaric acids with sodium carbonate or bicarbonate

• Uses: The liberated carbon dioxide has the following advantages:

• It masks the bitter and nauseous taste.• It promotes gastric secretions.• It acts as a carminative.• psychological impression at the patient..

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Special PowdersSpecial Powders1- Effervescent Powders1- Effervescent Powders

• Formulation:Formulation:- Bulk powders or divided powders- Bulk powders or divided powders- Packed in separate packages of - Packed in separate packages of contrasting colors.contrasting colors.- The contents are mixed in a quantity of - The contents are mixed in a quantity of water at the time of dosing.water at the time of dosing.- The liquid is consumed just after the - The liquid is consumed just after the reaction begin to subside.reaction begin to subside.

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Special PowdersSpecial Powders2- Effervescent Granules2- Effervescent Granules

• Definition:Definition: Sweetened effervescent Sweetened effervescent powders formulated as granules.powders formulated as granules.

• Granulation:Granulation: 1- Wet method:1- Wet method: By the addition of a By the addition of a binding liquid (Alcohol is frequently binding liquid (Alcohol is frequently used). used). 2- Dry method:2- Dry method: Heating effloresced Heating effloresced powder to liberate the water of powder to liberate the water of crystallization which then acts as the crystallization which then acts as the binding agentbinding agent

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Wet GranulationWet Granulation• Procedure: Procedure:

1-1- The powders are mixed without pressure in The powders are mixed without pressure in a suitable container.a suitable container.2-2- Alcohol is added in portions with stirring Alcohol is added in portions with stirring until a dough like mass is formed.until a dough like mass is formed.3-3- The materials are then passed through sieve The materials are then passed through sieve # 6.# 6.4-4- The resulted granules are dried at a The resulted granules are dried at a temperature not exceeding 50ºC.temperature not exceeding 50ºC.5-5- The granules are packed in air tight The granules are packed in air tight containerscontainers

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Dry granulationDry granulation• Procedure: Procedure: 1-1- All ingredients, except citric acid monohydrate, All ingredients, except citric acid monohydrate,

are dried and passed through sieve # 60.are dried and passed through sieve # 60.2-2- The powders are thoroughly mixed and citric The powders are thoroughly mixed and citric

acid crystals are added at last (un-effloresced acid crystals are added at last (un-effloresced citric acid contains one molecule of water of citric acid contains one molecule of water of crystallization).crystallization).

3-3- The mixture is spread in a shallow dish and The mixture is spread in a shallow dish and placed in an oven previously heated (99- placed in an oven previously heated (99- 105ºC). Upon heating citric acid crystals, the 105ºC). Upon heating citric acid crystals, the water of crystallization effloresces and citric water of crystallization effloresces and citric acid transforms to the powder form.acid transforms to the powder form.

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Dry granulationDry granulation

• Follow, Procedure: Follow, Procedure: 4-4- The use of a water bath surrounding the The use of a water bath surrounding the

beaker (or any container) in which the powders beaker (or any container) in which the powders are stirred is a more convenient method to are stirred is a more convenient method to prevent local over heating.prevent local over heating.

5-5- No stirring until the powders become moist No stirring until the powders become moist and form doughy mass.and form doughy mass.

6-6- The mass is then granulated by passage The mass is then granulated by passage through sieve # 6 and dried.through sieve # 6 and dried.

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• Packaging: Packaging: ** Effervescent granules or powders suffer Effervescent granules or powders suffer

from the short shelf life, especially if from the short shelf life, especially if they are filled into wide-mouthed screw they are filled into wide-mouthed screw capped containers.capped containers.

** Recently, the stability of effervescent Recently, the stability of effervescent granules and powders is greatly granules and powders is greatly improved by their packing in aluminum improved by their packing in aluminum bags tightly closed.bags tightly closed.

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Special PowdersSpecial Powders3- Dusting Powders3- Dusting Powders

It is a very fine, light powder for external used as It is a very fine, light powder for external used as an insecticide, medicine, toiletry, etc.an insecticide, medicine, toiletry, etc.

Requirements:Requirements: 1- 1- Homogenous and very fineHomogenous and very fine2- Free from irritation.2- Free from irritation.3- Flow easily.3- Flow easily.4- Have good covering capacity.4- Have good covering capacity.5- Have good adsorptive and absorptive capacity.5- Have good adsorptive and absorptive capacity.6- Spread uniformly over body surface.6- Spread uniformly over body surface.7- Cling (adhere) to skin surface after application.7- Cling (adhere) to skin surface after application.8- Protect the skin from irritation caused by friction, 8- Protect the skin from irritation caused by friction,

moisture and chemical irritants.moisture and chemical irritants.

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Application: Application: 1- 1- Medicated dusting powders may be applied either to

intact skin or to open wound and mucous membranes.

2- powders applied to open wound must be sterilized3- Particle size should be very small. It is better to be

micronized or those passes through # 100 sieve.4- Highly sorptive powders should not be used on areas

exude large quantities of fluids to avoid hard crust formation.

Function:Function: Lubricants- protective- adsorbents- antiseptic - astringents- antiperspirants

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Packaging:Packaging:Dispensed in sifter- top cans or pressurized packs (aerosols).Aerosols protect the powder from air, moisture and contamination and more convenient for application.

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• Example of dusting powder:Example of dusting powder:• IngredientIngredient

zinc oxidezinc oxide 250 g250 gstarch, in powderstarch, in powder 250 g250 gpurified talc, sterilizedpurified talc, sterilized 250 g250 g

Advice to patient:Advice to patient: the powder should be dusting lightly onto the powder should be dusting lightly onto the affected areathe affected area

Action and use:Action and use: absorbent dusting powder, mild antiseptic absorbent dusting powder, mild antiseptic

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Special PowdersSpecial Powders4- Insufflations4- Insufflations

Definition:Definition: Finely divided powders to be Finely divided powders to be blown into body cavities such as ears, blown into body cavities such as ears, nose, throat and vagina. nose, throat and vagina.

- - Drug and other ingredients are packed into hard Drug and other ingredients are packed into hard gelatin capsule. After insertion into the gelatin capsule. After insertion into the insufflator the shell is broken and the flow insufflator the shell is broken and the flow release of powder is controlled by the patient’s release of powder is controlled by the patient’s own respiratory effort.own respiratory effort.

Packaging:Packaging: - Insufflators (powder– blower) : difficult to (powder– blower) : difficult to

obtain a uniform dose.obtain a uniform dose.

powders,modified, lec 8

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