Chapter 6

Powder  Use to describe the physical form of a material : a dry substance composed of finely divided particles.  Use to describe a type of pharmaceutical preparation that is a medicated powder intended for internal (i.e., oral powder) or external ( i.e., topical powder ) use.  Are intimate mixtures of dry finely divided drugs and/ or chemicals that may be intended for internal or external use. 3 uses of medicate powders  Blended with powdered fillers and other pharmaceutical ingredients to fabricate solid dosage forms as tablets and capsules.  Dissolved or suspended in solvents or liquid vehicles to make various liquid dosage forms .  Incorporated into semisolid bases in the preparation of medicated ointments and creams. Granules  Granules are prepared agglomerates of smaller particles of powder. They are irregularly shaped but may be prepared to be spherical.  They are usually in the 4 – to 12- mesh sieve size range, although granules of various mesh sizes may be prepared depending upon their application. Powder Fineness  Vegetable and Animal Drugs      VERY COARSE (No.8) : All particles pass through a No. 8 sieve and not more than 20% pass. COARSE (No. 20): All particles pass through a No. 20 sieve and not more that 40% pass through a No. 60 sieve. MODERATELY COARSE (No. 40): All particles pass through a No. 40 sieve and not more than 40% pass through a No. 80 sieve. FINE (No. 60): All particles pass through a No.60 sieve and not more than 40% pass through a No. 100 sieve. VERY FINE (No. 80): All particles pass through a number No. 80 sieve. There is no limit to greater fineness.

 Chemicals     coarse (sieve no 20) - pass through sieve #20 not more than 60% through sieve #40 Moderately Coarse (sieve no. 40) - pass through sieve #40 and not more than 60% through sieve #60 Fine (Sieve no 80) - pass through sieve #80 and no limit to greater fineness Very Fine (Sieve no 120) - pass through sieve #120 and no limit to greater fineness

Factors influenced by particle size  Dissolution rate of particles –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 – ensure dose-to-dose contend uniformity.  Penetrability of particles – intended to inhaled for deposition deep in the respiratory tract.  Lack of grittiness of solid particles -in dermal ointments, creams, and ophthalmic preparations. Methods of Determining Particle size  SIEVING – particles are passed by mechanical shaking through a series of sieves of known and successively smaller size.  MICROSCOPY – sample particles are sized through the use of a calibrated grid background or other measuring device.  SEDIMENTATION RATE – determined by measuring the terminal settling velocity of particles through a liquid medium in a gravitational or centrifugal environment. May be calculated from Stoke’s law.  LIGHT ENERGY DIFFRACTION OR LIGHT SCATTERING – particle size is determined by the reduction in light reaching the sensor as the particle, dispersed in a liquid or gas, passes through the sensing zone.  LASER HOLOGRAPHY – a pulsed laser is fired through an aerosolized particle spray and is photographed in three dimensions with a holographic camera.  CASCADE IMPACTION – are separated into various size ranges by successively increasing the velocity of the airstream in which they are carried. Micromeritics  Is the science of small particles; is any unit of matter having defined physical dimensions. It is the study of a number of characteristics, including particle size and size distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent density and bulkiness. Different Ways of Comminution of Drugs  Trituration or Comminution – grinding a drug in a mortar to reduce its particle size. On a small scale  Levigation - is commonly used in small-scale preparation of ointments and suspensions to reduce the particle size and grittiness of the added powders. A mortar and pestle or an ointment tile may be used. A paste is formed by combining the powder and a small amount of liquid (the levigating agent) in which the powder is insoluble  Mineral oil and glycerine are commonly used levigating agents.

On a large scale  Various types of mills and pulverizers may be used to reduce particle size.  FitzMill Comminutor – used for particle reduction, with attached containment system for protection of environment and prevention of product contamination. Different Methods of Mixing Powders  Depending on the nature of the ingredients, the amount of powder, and the equipment, powders may be blended by spatulation, trituration, sifting, and tumbling. Spatulation  Blending small amounts of powders by movement of a spatula through them on a sheet of paper or an ointment tile. Trituration  may be employed both to comminute and to mix powders. If simple admixture is desired without the special need for comminution, the glass mortar is usually preferred. Sifting  Powders may also be mixed by passing them through sifters like those used in the kitchen to sift flour. Sifting results in a light, fluffy product. Tumbling  Another method of mixing powders is tumbling the powder in a rotating chamber.  Special small-scale and large-scale motorized powder blenders mix powders by tumbling them. Geometric Dilution Method  When a small amount of a potent substance is to be mixed with a large amount of diluent, the geometric dilution method is used to ensure the uniform distribution of the potent drug.  Used in mixing 2 ingredients of unequal quantities, where one begins with the smallest quantity and adds an equal quantity of the ingredient having the larger amount; process continues until all the ingredients are used Different routes of administering medicated powders  Some medicated powders are intended to be used internally and others, externally.  Most powders for internal use are taken orally after mixing with water or in the case of infants in their infant formulas.  Some powders are intended to be inhaled for local and systemic effects.  Other dry powders are commercially packaged for constitution with a liquid solvent or vehicle, some for administration orally, others for use as an injection, and still others for use as a vaginal douche.  Medicated powders for external use are dusted on the affected area from a sifter-type container or applied from a powder aerosol.

Advantages and Disadvantages of medicated powders  Medicated powders for oral use may be intended for local effects or systemic effects and may be preferred to counterpart tablets and capsules by patients who have difficulty swallowing solid dosage forms.  Advantage in terms of therapeutic response may be negligible or only minimal, depending on the drug release characteristics of the counterpart products.  A primary disadvantage of the use of oral powders is the undesirable taste of the drug. Requirements of Aerosolized Powders  The particle size of the micronized medication is prepared in the range of 1 to 6 μm in diameter.  In addition to the therapeutic agent, these products contain inert propellants and pharmaceutical diluents, such as crystalline alpha-lactose monohydrate, to aid the formulation’s flow properties and metering uniformity and to protect the powder from humidity Bulk Powders and Divided Powders  Dispensing powder medication in bulk quantities is limited to nonpotent substances.  Powders containing substances that should be administered in controlled dosage are supplied to the patient in divided amounts in folded papers or packets.  Bulk powders available in prepackaged amounts are  (a) antacids and laxatives, which the patient takes by mixing with water or another beverages before swallowing  (b) douche powders, dissolved in warm water by the patient for vaginal use;  (c) medicated powders for external application to the skin, usually topical anti-infective or antifungal  (d) brewer’s yeast powder containing B-complex vitamins and other nutritional supplements.  Commercially prepared premeasured products are available in folded papers or packets, includes  headache powders  powdered laxatives  and douche powders.

Block and Divide Method  The pharmacist places the entire amount of the prepared powder on a flat surface such as a porcelain or glass plate, pill tile, or large sheet of paper  With a large spatula, forms a rectangular or square block of the powder having a uniform depth.  Then, using the spatula, the pharmacist cuts into the powder lengthwise and crosswise to delineate the appropriate number of smaller, uniform blocks, each representing a dose or unit of medication.  Each of the smaller blocks is separated from the main block with the spatula, transferred to a powder paper, and wrapped. Ways of Preparing Granules  Wet Method  Dry Method Wet Method (Basic type)  Moisten the powder or powder mixture  Pass the resulting paste through a screen of the mesh size to produce the desired size of granules  The granules are placed on drying trays and are dried by air or under heat.  The granules are periodically moved about on the drying trays to prevent adhesion into a large mass Wet Method (Fluid Bed Processing)  Particles are placed in a conical piece of equipment  Vigorously dispersed and suspended while a liquid excipient is sprayed on the particles  Product dried, forming granules or pellets of defined particle size Dry Method  Dry powder is passed through a roll compactor then through a granulating machine  The compacted powder is granulated to uniform particle size in a mechanical granulator. Dry Method (Slugging)  Compression of a powder or powder mixture into large tablets or slugs on a compressing machine under 8,000 to 12,000 lb of pressure  The slugs are granulated into the desired particle size Characteristics of granules which are advantageous over powders  Granules flow well compared to powders  Granules are more stable to the effects of atmospheric humidity  Granules are more easily wetted by liquids

Chemical combination present in effervescent granulated salts  Effervescent salts are granules or coarse to very coarse powders containing a medicinal agent in a dry mixture usually composed of sodium bicarbonate, citric acid, and tartaric acid.  When added to water, the acids and the base react to liberate carbon dioxide, resulting in effervescence. Equation Involved  For Citric Acid:  3NaHCO3 + C6H8O7 .H2O → 4H2O + 3CO2 + Na3C6H5O7

 For Tartaric Acid:  2NaHCO3 + C4H6O6 → 2H2O + 2CO2 + Na2C4H4O6

Difference between Fusion method from the Dry method of preparing effervescent granules  In the fusion method, the one molecule of water present in each molecule of citric acid acts as the binding agent for the powder mixture  While in dry method, the powders are just being compressed.