powders and granules.pdf

POWDERS - intimate mixrture of dry, finelly divided drugs for external and internal use -limited preparations of medicines in powder form but used to create other dosage forms -starting point of all dosage forms ---------------------------------------------...

POWDERS - intimate mixrture of dry, finelly divided drugs for external and internal use -limited preparations of medicines in powder form but used to create other dosage forms -starting point of all dosage forms ------------------------------------------------------------------------------------------- Classification of powders (based on how we use the powder) Topical powders - should have a uniform, small particle size that will not irritate the skin when applied - target site: skin Characteristics: - impalpable (fine and smooth) and free flowing - easily adhere to the skin - passed through at least No. 100 mesh sieve to minimize skin irritation Composition: - talc/cornstarch (diluent) - magnesium/calcium/zinc stearate ( adherent) -active ingredient -aromatic materials Examples: Insufflated powders - applied in a body cavity (ears/nose/vagina) - used with an insufflator or puffer ------------------------------------------------------------------------------------------- Advantages: 1. flexibility in compounding (divided powder/paper tab) 2. relatively dry and devoid of moisture  3. stable 4. rapid onset of action Disadvantages: 1. Not easily wetted (not easily dispered/dissolve by the body), delayed efficacy 2. Inaccuracy of the dose 3. not suitable for dispensing (undergoes compounding for convenience/stability) 4. some are hygroscopic and deliquescent or fluorescent ------------------------------------------------------------------------------------------- Chemical and physical characterization A powder must pass the following characteristics: 1. Particle size (most important; affects solubility) 2. Solubility 3. Morphology 4. Purity 5. Stability 6. Uniformity 7. Compatibility 8. Flowability ------------------------------------------------------------------------------------------- Particle size analysis vegetable and animal origin 1. Very coarse (No.8) -not more than 20% pass through no.60 sieve 2. Coarse (no.20) -not more than 40% pass through no. 60 sieve 3. Moderately coarse (no.40) - not more than 40% pass through no. 80 sieve 4. Fine (no.60) -not more than 40% pass through a no. 100 sieve 5. Very fine (no.80) -there is no limit to greater fineness Chemical origin: 1. Coarse (no.20) - not more than 60% pass through no.40 sive 2. Moderately coarse (no.40) -not more than 60% pass through no.40 sieve 3. Fine (no.60) -no limit greater fineness 4. Very fine (no.120) -no limit greater fineness ------------------------------------------------------------------------------------------- Factors in determining and classify the powders based on particle size: 1. Dissolution rate of particle - the smaller the particle size results to higher dissolution rate 2. Suspendability of particles -uniform suspendability to have uniform dosing (suspensions) 3. Distribution uniformity of the substances -uniform dosing, uniform distribution 4. Penetrability of particles -not uniform particle size does not penetrate to the target organ 5. Lack of grittiness of solid particles ------------------------------------------------------------------------------------------- Methods of particle size determination A combination of methods is preferred to provide a greater cetainty of the particle size 1. Sieving -particles are passed by a mechanical shaking through a series of sieves -simplest method -generally made of wire cloth woven from brass, bronze or other suitable wire -not coated or plated -stacked from the biggest holes to the smallest holes -mechnical shaker shakes the sieves 2. Microscopy -sample particles are size through the use of calibration grid background or other measuring devices -extesive method 3. Sedimentation rate -measuring the terminal settling velocity of particles through a liquid medium, gravitational or centrifugal environment -factor affecting: gravity -calculated: stokes' law 4. Light energy diffraction/light scaterring -reduction in light reaching the sensor as particles as dispersed in a liquid or gas passes through the sensing zone -set-up: light source-solution/powder/sensor (large amount of light reached the sensor: small particle size) (small amount of light reached the sensor: big particle size) -light source: helium and neon laser -detector: silicon photo or ultrasonic probe 5. Laser holography -pulsed laser is fired through an aerosolized particle spray and is photographed in 3D with holographic camera allowing the particles to be imaged and size -more advanced technology 6. Cascade impaction -particle driven by an air stream will hit the surface in its path ------------------------------------------------------------------------------------------- Comminution of Drugs -reducing of particle size 1. Trituration/comminution -grinding a drug in a mortar to reduce its particle size -usually conducted in a small scale Types of mortar and pestle a. Glass - used for solutions/suspensions/ointments b. Wedgewood - used for crystalline solid c. porcelain - used for soft aggregates/crystals; preferred in the laboratory for finer grider action 2. Levigation -used in small-scale preparation of ointments and suspensions to reduce the particle size and grittiness of added powders -used for paste, creams and ointments -levigating paste+ointment base = ointment -levigating paste+cream base= cream -paste is formed by combining the powder and a small amount of liquid (levigating agent) in which the powders are insoluble -equipment: spatula/ointment tile/glassine paper/wax paper -figure 8 track is commonly used to incorporate materials in levigation process with the use of mortar and pestle  -levigating agent: mineral oil, glycerin) 3. Pulveration by intervention - process of reducing particle size with the aid of volatile solvent which can be remove easily after pulveration -intended for gummy, sticky like materials that resist grinding -ex: camphor+alcohol; iodide crystal+ ether ------------------------------------------------------------------------------------------- Blending of powders 1. Spatulation -little compression -blending of small powders -not suitable for large quantity of powders and powders of potent substances -suitable for eutectic mixture -spatula and ointment slab is used more often 2. Trituration -employed both to comminute and to mix powders -Involves comminution and blending -geometric dilution: used when a small potent drug to be mixed with a large amount of diluent; when active ing. and inert ing. is to be mixed and no visible sign of mixing 3. Sifting -mixed by passing them through sifters -disadvantage: not suitable for potent drug and not suitable for incorporation of drugs 4. Tumbling -mixed in a rotating chamber -thorough but time consuming -for large scale  -equipment: ribbon blender or v-shaped blending equipment ------------------------------------------------------------------------------------------- Undesirable in blending of powders Segregation -separation of the different components of the blends Occur in: 1. Sifting or percolation -fine particles are lifted while larger particles are the bottom or vice versa 2. Air entrapment (fluidization) 3. Particle entrapment (dusting) -when the finer particles are suspended in the air for a long period of time, and do not settle quickly compared to larger particles Ways to prevent segregation: 1. Minimize number of transfer steps and drop heights 2. Control dust generation (vacuum transfer) 3. Control fluidization of the powder 4. Slow fill/transfer rate 5. Appropriate venting 6. Use of deflector, vane or distributor 7. Proper hopper design and opening valves ------------------------------------------------------------------------------------------- Types of powders 1. Eutectic - powders become sticky or pasty or may liquify when mixed together because of their different melting point -remedy: addition of light magnesium oxide or magnesium carbonate (adsorbing powders) 2. Hygroscopic  -powders that absorb moisture from the air -remedy: dispense in a tight container with dessicant packets 3. Deliquescent -powders that absorb moisture from air and liquefy -remedy: dispense in a tight container with dessicant packets 4. Efflorescent -crystalline powder that contains water of crystallization -remedy: use the anhydrous form of the drug; include a drying bulking powder and use light noncompacting method of mizing 5. Explosive -powders that react violently when mixed together -remedy: do not mix and place it indifferent containers ------------------------------------------------------------------------------------------- Medicated powders/ pharmaceutical powders 1. Aerosol powders -administered with the aid of inhalers which delivers micronized drugs in metered quantities 2. Dusting powders -intended to be dusted on the skin by sprinkling or sifter-top containers 3. Douche powders -preparation of vaginal douche; for hygienic/antiseptic effect 4. Oral powders 5. Detrifices  -mild abrasive action; employed as anti-cariogenic 6. Insufflation powders 7. Trituration powders 8. Divided powders (chartulae, charts, papertabs, papelitos) -known as individualize powders and can be prepared by weighing each portion or block and divide method Types of paper used: -simple bondpaper - moisture resistance -vegetable parchment - thin semi-opaque with limited moisture resistance -glassine paper - transparent/limited moisture resistance -waxed paper - transparent waterproof used for hydroscopic or deliquescent powder ------------------------------------------------------------------------------------------- GRANULES -agglomerates of powdered materials -prepared by: a. dry method/dry granulation b. wet method/wet granulation -usually has a mesh size/sieve size of 4-12 Advantages (over powder): 1. Flows well -facilitate the transport of the drug material to hopper to the tablet press 2. Less surface area -more stable from atmosphere humidity and less tendency to cake or harden 3. Easily wetted -suitable for material that needs reconstitution prior to use ------------------------------------------------------------------------------------------- Methods of granulation 1. Wet granulation (fluid bed processing) Advantage: a. increase compressibility b. improve dissolution Disadvantage: a. not applicable for moisture and heat sensitive drug 2. Dry granulation (roll compactor/slugging) -particles are aggregated using high pressure -easier process compared to wet granulation Advantage: a. no liquid binder is added b. eliminate wetting and drying steps c. suitable for drugs that do not compress well after granulation d. suitable for heat and moisture sensitive labile drugs ------------------------------------------------------------------------------------------- Effervescent granulated salts - dosage form that when in contact with water, rapidly release carbon dioxide (which fastens the dissolution rate of the granules and it gives and enhances the flavor ) -effervescent salts are granules or coarse to very coarse powders containing medicinal agent in a dry mixture Composition: 1. Sodium bicarbonate 2. Citric acid  3. Tartaric acid The 3 compositions must be present always. If one is lacking it may result to: sodium bicarbonate + citric acid = sticky sodium bicarbonate + tartaric acid = easily crumble/crushed