Powders and granules.pdf

Powders and Granules Powders physical form: a dry substance composed of finely divided particles. type of pharmaceutical preparation: medicated powder intended for internal or external use. Powders are intimate mixtures of dry, finely divided d...

Powders and Granules Powders physical form: a dry substance composed of finely divided particles. type of pharmaceutical preparation: medicated powder intended for internal or external use. Powders are intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended for internal or external use. The use of medicated powders in preparation of other dosage forms is extensive. may be blended with powdered fillers and other pharmaceutical ingredients to fabricate solid dosage forms as tablets and capsules. The use of medicated powders in preparation of other dosage forms is extensive. may be dissolved or suspended in solvents or liquid vehicles to make various liquid dosage forms. The use of medicated powders in preparation of other dosage forms is extensive. may be incorporated into semisolid bases in the preparation of medicated ointments and creams. Particle Size and Analysis USP uses descriptive terms to characterize particle size -very course -fine -course -very fine -moderately course Sieves- generally made of wire cloth woven from brass, bronze or other suitable wire Purpose obtain quantitative data on the size, distribution, and shapes of the drug and other components to be used in pharmaceutical formulations. Important factors that a particle size can influence Drug micronization can increase the rate of drug dissolution and its bioavailability Suspendability of particles intended to remain undissolved but uniformly dispersed in a liquid vehicle Uniform distribution of a drug substance in a powder mixture or solid dosage form to ensure dose-to-dose content uniformity Penetrability of particles intended to be inhaled for deposition deep in the respiratory tract Lack of grittiness of solid particles in dermal ointments, cream, and ophthalmic preparations. Methods for determining particle size Sieving–passed through series of sieves  Microscopy–size through the use of calibrated grid background Sedimentation Rate - measuring the terminal settling velocity through a liquid medium in a gravitational environment - Stoke’s Law Light energy diffraction – reduction in light reaching the sensor as the particle, dispersed in a liquid or gas, passes through the sensing zone Laser Holography–pulsed laser fired through an aerosolized dimensions with a holographic camera Cascade Impaction – separated into various size ranges by successively increasing the velocity of the airstream in which they are carried. – a reduction in particle size increases the number of particles and the total surface area Comminution of Drugs Small Scale: Trituration–grinding drug in a mortar to reduce its particle size Levigation–preparation of ointments and suspensions to reduce particle size and grittiness of the added powders Large Scale: Mills and Pulverizers – FitzMill – grinding action of rapidly moving blades, particles are reduced in size and passed through a screen of desired dimension to the collection container Blending Powders Spatulation – blending small amounts of powders by movement of a spatula Trituration – may be employed both to comminute and to mix powders Geometric Dilution – mixing a small amount of potent substance with a large amount of diluent / ensure the uniform distribution of the potent drug Sifting – powders are passed through sifters, resulting in a light and fluffy product Tumbling – tumbling the powder in a rotating chamber Segregation – undesirable separation of the different components of the blend – Occurs by sifting or percolation,air entrapment (fluidization), particle entrapment (dusting) – Fineparticlestendtosiftorpercolate through course particles and end up at the bottom of the container and lift the larger particles to the surface – Dusting occurs when the finer, lighter particles remain suspended in air longer and do not settle as quickly as the larger or denser particles. Guidelines to minimize/ prevent segregation Minimumnumberoftransferstepsand drop heights Control Of Dust Generation Control Of Fluidization Of Powder Slow fill/transfer rate Appropriate Venting Use of a deflector, vane or distributor  Proper hopper design and operating valves Can be taken: 1. Internally 2. Externally INTERNALLY Taken orally after mixing with water (or in milk formulas in the case of infants) *reconstitution Can be inhaled for local or systemic effects EXTERNALLY Dusted on the affected area from a sifter- type container Applied from a powder aerosol Should bear the label “EXTERNAL USE ONLY” ADVANTAGES For patients who have difficulty in swallowing tablets or capsules Drugs are too bulky to be formed as tablets May be expected to result in FASTER RATES of dissolution and absorption than solid dos. forms DISADVANTAGE May be undesirable in taste Unstable in liquid form (in which case, the manufacturer will distribute it as dry powders for constitution; stable for max of 14 days) AEROSOL POWDERS Powders that are administered by inhalation With aid of DRY-POWDER INHALERS-delivers micronized particles of medication in metered quantities Most are used in the treatment of asthma and other bronchial disorders 1 to 6 mcm- (in diameter) particle size of micronized medication. Crystalline alpha-lactose monohydrate - Pharmaceutical diluent that aids in formulation’s flow properties and protects from humidity. Powder blowers or insufflators -may be used to deliver powders to various parts of the body. BULK AND DIVIDED POWDERS BULK POWDERS: a) Antacid b) Douche powders c) Med powders for external applic. d) Brewer’s yeast powders -limited to non potent substances -stored at room temp in a clean, dry place. -kept out of reach of children and animals DIVIDED POWDERS -for potent substances -ready to take -in a variety of small pieces of paper (chartulae) Commercially available products: BC powders- for headache Psyllium mucilloid- laxative Massengill powder rackets-douche powders Method of preparation: -weigh each portion of powder separately before enfolding in a paper -bock-and-divide method (for non potent subs only) Types of papers used: a) Vegetable parchment -semi-opaque, moisture resistant. b) White bond paper- opaque, no resisting properties c) Glassine-glazed, transparent, moisture resistant d) waxed- transparent waterproof Granules prepared agglomerates of powdered materials used for the medicinal value of their content used for pharmaceutical purposes (making tablets, etc.) flow well compared to powders more stable to atmospheric humidity less likely to cake or harden upon standing Irregularly shaped but may be prepared to be spherical Usually in the 4- to 12-mesh sieve size range Prepared by wet and dry methods WET METHOD May be done in 2 ways: – basic wet method – fluid bed processing (preblending, granulation, drying) Application: drugs which are stable with moisture; for powdered materials which are not compressible Moisten the powder (powder mixture) and then pass the resulting paste through a screen of the mesh size to produce the desired size of granules  Granules are placed on drying trays and dried by air or heat. Fluid bed processing – particles placed on a conical piece of equipment, vigorously dispersed and suspended while a liquid excipient is sprayed on the particles and the product dried, forming granules or pellets of defined particle size. DRY METHOD powder mixture is compacted in large pieces & subsequently broken down & sized into granules may be done in 2 ways: – roller compactor & granulating machine – Slugging Application: heat & moisture- sensitive drugs – ASA, Vit C, Vit B1 Passed through a roll compactor (roll press) – process a fine powder into dense sheets by forcing it through two mechanically rotating metal rolls running counter to each other. SLUGGING compression of powder into large tablets or “slugs” on a compressing machine under 8,000 to 12,000lb of pressure Slugs: flat-faced and about 2.5cm(1in.) in diameter Granulated into the desired particle size, for the production of tablets Production of fines – powder that has not agglomerated into granules (separated, collected and reprocessed) EXAMPLES Biaxin granules (clarithromycin, oral suspension) Omnicef (cefdinir, oral suspension) Augmentin ES-600 (amixicillin/ clavulanate K) Ceftin (cefuroxime axetil, Oral suspension) Lactinex granules (lactobacillus acidophilus, lactobacillus bulgaricus) – treatment of uncomplicated diarrhea and diarrhea due to antibiotic therapy Zantac EFFERdose tablets – compressed granule effervescent EFFERVESCENT GRANULATED SALTS granules of coarse to very coarse powders containing a medicinal agent in a dry mixture composed of – sodium bicarbonate – citric acid – tartaric acid effervescence from the released CO2 masks the undesirable taste of drugs. tartaric acid alone -granules readily lose their firmness & crumble citric acid alone - results in a sticky mixture which is difficult to granulate prepared by: – dry or fusion method – wet method Dry or fusion method One molecule of water present in each molecule of citric acid acts as the binding agent for the powder mixture Granules are dried not exceeding 54°C and immediately placed in tight sealed containers – Acetaminophen for Effervescent Oral Solution USP WET METHOD The source of binding agent is not the water of crystallization from the citric acid but the water added to alcohol as the moistening agent, forming pliable mass for granulation