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39 Cards in this Set
- Front
- Back
Definition: Powders and Granules
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USP Definition of Powders: "Powders are intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended (oral powders) for internal or external (topical powders) use"
-Powders are mixtures Granules: granules are prepared agglomerates of powders e.g. bakery product: add water-->serves as glue--> powder becomes globules --> granules |
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Properties of Powders
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As a dosage form, a powder is a mixture of "powdered" drugs and excipients
A dosage form, different from "powder" or "powdered" a physical state Use as a dosage form is limited Extensively used in most dosage forms dosage form = pharmaceutical product in certain form |
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Why Study Powders?
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1. Existing in powder form: active pharmaceutical ingredient (API) and excipient (inactive ingredient)
2. Pharmaceutical preparations: topical powder or sterile powder in vial 3. Starting material for -solid dosage form - tablet, capsule -liquid dosage form - powder for reconstitution -semisolid dosage form - ointment or cream |
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Characterization of Powders
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-Mainly physical
-Morphology (shape) e.g. needle-shaped vs. spherical --> affect drug in diff. ways -Purity -Solubility -Stability -Particle size and distribution -Uniformity (after mixing) -Compatibility in blends |
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Common issues with powders
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Powders can cause issues in:
-Dissolution rate - if powder is large particles --> diss. rate = slow. If powder is smaller particles --> diss. rate = faster -Suspension -Uniform distribution - need to have uniformity -inhalation - powder needs to be light enough to go into lung but can't be too light otherwise it will be exhaled. If too large, can't suspend in air -Poor flow -Appearane Thus, needs to characterize powder particle size and distribution. |
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Characterize Powder Particle Size
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Sieve analysis: sieve number or mesh size - size
USP description -very coarse: number 8 -coarse: number 20 -moderately coarse: number 40 -fine: number 60 -very fine: number 80 Granules: coarse to very coarse (8-40) Increase in number - finer particles |
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Characterize Powder Particle Size
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-Microscopy
-Sedimentation rate -Light scattering -Casacade impact - for aerosol |
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Particle Size Reduction-Comminution
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Why reduce particle size?
-increase dissolution -increase extraction -increase uniformity -enhance absorption Mortar and pestle: trituration (grinding) Levigation: grinding particles in oil with mortar and pestle. Ointment or paste preparation Mills: cutting and sieving, e.g. FitzMill --> very common in industry Pulverizer: grinding |
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Blending Powders
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Blending: mixing powders to uniform
-Spatulation: small -Trituration: small -Sifting: industry -Tumbling: industry -Geometric dilution: blending potent drug in small equal portion of diluent, repeat steps till finish diluents --> used in industry and pharmacy Mg stearate = lubricant |
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Medicated Powders (Definition by Application)
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-Oral powder for reconstitution: for ease of swallow, or large dose, e.g., oral antibiotics liquid, label storage (2 weeks). Needs taste masking
-Dry powder inhalation -Sterile dry powder: reconstitute with water for injection -Vaginal douche: reconstitute with water, label "external use only" |
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Example of Powder Applications (1 of 2)
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-Particles are important to suspensions
-Both the physical stability and bioavailability of suspensions can be related to the particles size -Large particles can not be suspended for long -Large particles may reduce the bioavailability |
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Example of Powder Applications (2 of 2)
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-In inhalation aerosols, particle size is critical to achieve maximum penetration and deposition into the deeper airways of the lung
-85% of particles >5 micrometers are retained in the upper respiratory tract -90% of particles in the 1-5 micrometer range are reained in the alveolae -Particles <0.5 micrometers are exhaled -Optimum particle: not too big, no too small sizes --> 5 micrometers |
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Powders for external use (1 of 2)
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-Topical application: dusting powders
-Common diluents are starch and talc -Easily applied in sifter-top shaker containers -Most sifter-top containers are not "tight containers" -Not volatile or sensitive to moisture components -Examples: Methylbenzethonium Chloride Powder, USP --> not common. Historical product. Produced by trituration. Nystatin Topical Powder, USP |
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Powders for external use (2 of 2)
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The mechanical irritation of topicals )dusting powders, creams and ointments) depends on particle size
-Particles pass through 325 mesh sieve (smaller than 45 micrometers) can minimize mechanical irritation |
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Bulk and Divided Powders (Definition by Packaging) (1 of 2)
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-Bulk powders - nonpotent powders
-Antacids or laxatives: take with water -Douche powders: wash with water, for vaginal use -Topical powder: anti-infectives, antifungals -Brewer's yeast powder: B complex vitamins -Prepackaged -Measuring tools: spoons or scoops |
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Bulk and Divided Powders (Definition by Packaging) (2 of 2)
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-Divided Powder: for unit dose or each use
-Divide powder: weighing or block-and-divide -Pack each divided portion in paper -Select waxed or glassine paper in packing if moisture or air sensitive, or volatile |
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Divided Powders
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Latin chartulae (pl._; Abbreviation: charts.
-'Powder Papers' -After mixing, the powder blend is divided into individual units -The portions are each placed on a small piece of paper, and folded to enclose (powder papers) -Traditionally, the powder packets are dispensed in a cardboard "Powder Box" |
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Granules
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-Granules are prepared agglomerates of powders
-Granulation is a size enlargement process -Irregular shape, not spherical -Size: usually 4-12 sieve number -But vary dependent on applications -Granules are larger and more porous than powder -Starting material for -solid dosage form - tablet, capsule -liquid dosage form - powder for reconstitution |
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Why Granules (1 of 4)
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-Good flow: large size than powder --> powder is coming in steadily --> powders cannot achieve this but granules can
-Compressibility: contains binder -Uniformity: drug and excipient are binded --> porous has more compressibility -Making tablets or filling capsules -Advantage in feeding high-speed equipment -Form plug when making capsules -Need to mix powder well to makes granules |
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Why Granules (2 of 4)
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-Larger size than powders
-Less surface area per unit weight than powders (the smaller, the larger surface area) -More stable to atmospheric moisture or oxygen -Less likely to cake in the container than powders |
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Why Granules (3 of 4)
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-granulation may improve drug dissolution (e.g. from a tablet)
-enhancing wettability due to hydrophilic nature -the hyrophilic binder, which covers particle -more porous, capillary action (sucking) readily wetted vs powder -attract water due to above mechanisms and can enhance the ability of hydrophobic, poorly soluble drugs to be wetted by dissolution fluids. |
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Why Granules (4 of 4)
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Generally difficult to mix low dose drugs to uniformity
-Wet granulation can ensure content uniformity -In wet granulation, drugs can be dissolved or dispersed in binder solution -Adding liquid phase helps dispersion of low dose drug to ensure content uniformity -After drying, drug is locked in granules -This feature is important to achieve content uniformity for tablets or capsules. |
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Granules
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-May be dispensed in bulk as a dosage form for oral administration, e.g. antibiotics, antacid, dietary supplement etc.
-Widely used as an intermediate for making compressed tablets. Powders may also be granulated prior to filling into capsules (flow and uniformity) |
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Granule Composition
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Main composition
-active ingredient -diluent - makes up bulk volume -binder - if no binder, one dry --> becomes loose -flavor (powder for reconstitution) -color (powder for reconstitution) |
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Granule Preparation: Wet Granulation
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Fluid in wet granulation: high shear or fluid bed dryer.
High (or low shear) mixer process -Moist and mix powders to form liquid bridge among powders -Powders stick together in lumps -Wet lumps pass through sieve -Wet granules are tray dried in oven or dried in fluid bed dryer -Pass dried granulation through sieve |
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High Shear Granulator
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-Revolutionized pharm. industry
-Collette Gral Type -High speed -Bowl |
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Granule Preparation: Wet Granulation
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Fluid bed dryer process
-Fluid bed dryer is a conical shaped equipped to perform all steps -Air suspends powders for mixing -Spay granulation fluid to moist and mix powders to form liquid bridge among powders -Wet granules are dried by suspending in hot air |
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Fluid Bed Granulation
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-Requires balance of inlet air temperature and feed rate
-Higher inlet air temperature cause rapid evaporation of the binder solution and results in smaller, friable granules -Lower inlet temperatures, drying is slower (particles star wetter longer); produces larger, denser, stronger granules -Higher feed rates increases the 'evaporative load' and slows drying; tends to produce larger, denser and stronger granules -Lower feed rates tend to produce smaller, friable granules |
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Caution
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Wet granulation is not practical for drugs sensitive to water or heat (hydrolysis)
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Granule Preparation: Dry Preparation: Dry Granulation
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-No fluid in dry granulation: roller compactor or slugging
-Roller compactor method: 1. Compact powders to ribbons 2. Break ribbons to granules of desired size -Slugging Method: 1. Compact powders to large tablets or slugs (about 1 inch in diameter) 2. Break slugs to granules of desired size |
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Dry Granulation - Slugging
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-Older process
-Mix with dry binders -Compress into large crude tablets (slugs) on a special heavy duty slugging press -Mill the slugs to form granules -Slugging is slow and may require double lubrication (could slow drug dissolution) |
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Dry Granulation - Roller Compaction
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-Powder blend is compressed between rollers to form a cake (ribbon)
-Cake milled to form granules -Compact formation facilitated by *increased time under pressure facilitates bonding between particles *use of highly compactible excipients that can effectively function as dry binders *Microcrystalline cellulose |
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Granules Applications
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-Granules have broad applications due to good flow, compressibility, uniformity
-Manufacturing tablet, or capsule -More porous, readily wetted vs powder -Packaged as a powder for reconstitution (antibiotics) -More stable vs powder (small surface area to humidity) |
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Granules Applications
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-Reconstituted antibiotics
-Bulk laxatives, e.g. Senokot Granules (granules contain standardized senna concentrate) -Bulk analgesics, e.g., effervescent granules such as Bromo Seltzer |
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Powder for Reconsitution Dose Calculation
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Refer to slides
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Effervescent Granulated Salts (1 of 2)
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Package granules for high dose, masking taste, ease of swallow
-Main ingredients: acid, base, and the active ingredient -Acid: combination of citric acid and tartaric acid to avoid stickiness (citric acid) or crumbling (tartaric acid) -Base: sodium bicarbonate -Granulate to control the rate of solution and effervescence |
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Effervescent Granulated Salts (2 of 2)
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-Carbon dioxide forms with placed in water
-Carbonation helps mask the unpleasant taste of drugs -Granular form (as opposed to powder form) -Dissolves more slowly and provides a more controlled reaction -More stable to atmosphere |
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Effervescent Granules: Fusion Method
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-No water added
-Water is in citric acid crystal (citric acid monohydrate) -Mix powder -Dry at 34-40 degrees Celsius to release water from citric acid crystal, trigger chimical reaction -Water released and chemical reaction product (water and CO2) granulate powders upon mixing -Sieve -Dry at 54 degrees Celsius -Air tight packaging |
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Effervescent Granules: Wet Method
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-Binding agent: water and alcohol
-Powers are anhydrous -Granulate with just enough water without triggering effervescence -Sieve -Dry -Package |