St. Alexius College PDF - Powders and Granules

PCTS1-DDS Powders and Granules Jefferson A. Chanco Objectives After reading this chapter, the student will be able to: 1. Differentiate a powder from a granule 2. Explain how a drug's powder particle size influences the pharmaceutical dosage forms that will be used to administer it 3. D...

PCTS1-DDS Powders and Granules Jefferson A. Chanco Objectives After reading this chapter, the student will be able to: 1. Differentiate a powder from a granule 2. Explain how a drug's powder particle size influences the pharmaceutical dosage forms that will be used to administer it 3. Define micromeritics, the angle of repose, levigation, spatulation, and trituration 4. Compare and contrast the various types of medicated powders, for example, bulk, divided 5. Provide examples of medicated powders used in prescription and nonprescription products 6. Differentiate between the fusion method and wet method for the preparation of effervescent granulated salts Powders and Granules Powders Medicated powders Granules Quality control Packaging/dispensing Patient counseling Powders Particle size and analysis Comminution of drugs Blending powders Medicated Powders Aerosol powders Bulk and divided powders – Bulk powders – Divided powders Granules Effervescent granulated salts – Fusion method -drugs and other solids are dissolved in an ointment base and then combined – Wet method -process of size enlargement in which a liquid is added to a powder with agitation to produce agglomeration or granules. Powders Particle Size and Analysis Very coarse #8 sieve 2,360 μm 2.36 mm Coarse #20 sieve 850 μm 0.85mm Mod. coarse #40 sieve 425 μm Fine #60 sieve 250 μm Very fine #80 sieve 180 μm Particle Size Dissolution Suspendability of suspensions Uniformity of mixtures in liquids Penetrability of particles for inhalation Nongrittiness for ointments, creams, gels Particle Size (cont.) If uniform, will aid in mixing and distribution. Finer particles may migrate to bottom. Larger particles may migrate to top. Differences may change the color intensity of a powder. Especially important in dermatologicals. Comminution of Drugs Comminution of Drugs The process of reducing the particle size of a solid substance to a finer state of subdivision. Stone mills were the original implement for grinding. Mortars and pestles are the symbol of pharmacy. Objectives of Comminution Facilitate crude drug extraction Increase the dissolution rates of drugs Aid in the formulation process Enhance absorption Methods of Comminution Manual Mechanical Manual Methods of Comminution Trituration (to rub to pieces) – Pill tile and spatula – Mortar and pestle Porcelain Wedgewood Glass Manual Methods of Comminution (cont.) Levigation to make smooth – Triturating while moistened with a liquid in which the powder is insoluble Pulverization by intervention – Comminution by utilizing a solvent that can be easily removed Mechanical Methods of Comminution Ball mills – Closed – Continuous Roller mills Cutter mills Hammer mills Colloid mills Mechanical Methods of Comminution Ball mills- size reduction is done by impact as the balls drop from near the top of the shell. Roller mills- uses cylindrical rollers to crush and grind material Cutter mills- involves successive cutting or shearing the materials with the help of sharp knives Hammer mills- crushes material into smaller pieces by the repeated blows of little hammers. Colloid mills- decrease the particle size of an insoluble material in suspension, either in liquid or in emulsion. Mechanical Methods of Comminution (cont.) Fluid energy mills- rely on collisions in a stream of particles entrained in a high-velocity fluid, typically air or steam, to effect breakage. Lyophilization (freeze-drying) Spray drying  Cutter Mill Ball Mill Hammer Mill Roller Mill Colloid Mill Fluid Energy Mill Lyophilizer Spray Drying Blending Powders When Preparing Dosage Forms Reduce particle size until uniform with other ingredients. Start with the substance present in the smallest amount and add ingredient with next larger quantity (if practical) using geometric dilution technique. Also “tracer” method. Continue adding substances until all are added and uniformly mixed. Blending (Mixing) A process that tends to result in a randomization of dissimilar particles within a system 1. Small-scale blending equipment – Compounding 2. Large-scale blending equipment – Manufacturing Small-Scale Blending Equipment Pill tile and spatula Mortar and pestle Bottle/container Plastic baggie Easily cleanable Dust tight Provide complete discharge/recovery Mixing Mechanisms Convective mixing Shear mixing Diffusive mixing Equipment Categories Batch mixing Continuous mixing Tumblers – Double-cone blender – Twin-shell blender Paddle blenders – Blade and paddle blender Factors in Blending Size Shape Density Electrostatic forces Limits of blend Segregation mechanisms Medicated Powders Powder Applications Dentifrices – Powders used to clean the teeth Insufflations – Intended for application to the body cavities (e.g., tooth sockets, ears, nose, throat, vagina) Powder aerosols – Antiperspirants, deodorants, feminine hygiene sprays, body sprays, insufflations, dry lubricants Aerosol Powders Inhalation Dry-powder inhalers Micronized powders External application and nose, throat, lung, and vagina Insufflators Powder blowers Oral inhalation Bulk and Divided Powders Powders: Categories Bulk powders – Intended to be administered in dosage quantities that are safe for the patient to measure – Should pass through a 100-mesh sieve – Dusting powders, aerosols, dentifrices, antacids, laxatives, dietary nutrient supplements, douches Dusting Powders Must be homogenous, free from potential of causing local irritation Should flow easily, spread uniformly, and cling to the skin upon application Generally dispensed in sifter-top containers Powders: Categories Divided powders (chartula, charts, powder papers, powders) – Single doses of the powdered drug mixture individually enclosed in paper, cellophane, or metallic foil wrappers or packets – Sufficiently potent to require premeasured doses Advantages of Divided Powders 1. Allows physicians to prescribe a precise amount of the drug. 2. More stable than the liquid form of many drugs. 3. Dissolve more rapidly than compressed solid dosage forms. 4. Rapid dissolution leads to faster blood levels and possibly less GI irritation. Applications Easily alter dose Clinical studies, easy to prepare and alter Infants/young children (“sprinkles”) Bulky drugs Rapid onset of action, good bioavailability Stable Disadvantages of Powders 1. Not suitable for bitter, nauseating, or corrosive drugs 2. Preparation is time consuming, therefore more costly 3. Exposure of powder to atmospheric conditions Preparation of Powders Spatulation Trituration Sifting Tumbling Dividing Powder Mixtures into Unit Doses Weighing each powder Blocking and dividing Powder measures Volumetric template Chart Preparation A chart should fold readily, hold its form, remain clean with handling, protect contents from atmosphere, be water-repellant, and present an elegant appearance. Parchment, glassine, waxed paper Bond paper Double wrapping Preparation Techniques Potent drugs Incorporation of liquids Volatility Hydration, crystal hydrates Hygroscopic and deliquescent powders Efflorescent powders Water of imbibition Eutectic mixtures Potent Drugs Rx – Atropine sulfate 0.4 mg – Mft Pwdr #1, DTD #XII Sig: i 15 min ac. Incorporation of Liquids Rx – Belladonna tincture 0.6 mL – Acetaminophen 300 mg – M. Disp. Cap. #10 Incorporation of Liquids (cont.) Rx – Belladonna extract – Phenobarbital aa 0.4 – Bi subnitrate 24 – Kaolin 45 – Peppermint oil 0.12 – Sig: drams I ac until diarrhea subsides. Volatility Camphor Iodine Menthol Hydration, Crystal Hydrates Depending upon the humidity, a salt hydrate may: – Remain unchanged – Deliquesce – Effloresce Hygroscopic and Deliquescent Powders Hygroscopic – Substances that absorb moisture from the air Deliquescent – Substances that absorb moisture from the air to the extent that they liquefy by partially or wholly forming a solution Examples: Hygroscopic and Deliquescent Powders Ammonium bromide/chloride/iodide Calcium bromide/chloride Ephedrine sulfate Hyoscyamine HBr/sulfate Lithium bromide Phenobarbital sodium Potassium acetate/citrate Sodium bromide/iodide/nitrate Physostigmine sulfate/HCl/HBr Pilocarpine Efflorescent Powders Crystalline substances that become powdery and liberate their water of crystallization Alums, atropine sulfate, caffeine, calcium lactate, citric acid, cocaine, codeine phosphate/sulfate, ferrous sulfate, morphine acetate, scopolamine HBr, sodium acetate, sodium carbonate, sodium phosphate, strychnine sulfate, terpin hydrate Water of Imbibition Colloidal substances may absorb large amounts of water and retain the appearance of dry powders. This may cause problems in weighing. The water content varies with the humidity. Cellulose, starch, agar, gelatin. Eutectic Mixtures A proportion of components that will give the lowest melting point A mixture of components with a melting point less than room temperature Aspirin, beta-naphthol, camphor, chloral hydrate, menthol, phenol, salol, thymol Avoiding Eutectics 1. Dispense powders separately. 2. Add an absorbent powder (talc, starch, lactose, calcium phosphate). 3. Keep ingredients separated as much as possible. 4. Make the eutectic, and then add absorbent to incorporate the liquid. Explosive Mixtures When triturating an oxidizing agent with a reducing agent (using a mortar and pestle) Oxidizing agents – Potassium chlorate/nitrate/permanganate, sodium peroxide, silver nitrate, silver oxide Reducing agents – Charcoal, hypophosphites, sulfur, sulfides, tannic acid, volatile oils Dusting Powder (cont.) Applied to intertriginous areas as a covering to protect the skin from chafing of friction and moisture Vehicles: Bentonite, kaolin, kieselguhr, magnesium carbonate, starch – Note: These vehicles will absorb secretions and dry the area and impart a cooling effect. Dusting Powder (cont.) The following will impart adhesiveness to the powder: – Aluminum stearate, kaolin, magnesium stearate, zinc oxide, zinc stearate Granules Granules Particles ranging from 4 to 10 mesh in size Not intended for use with potent drugs because of inherent error when a patient measures the dose with a teaspoon, scoop, etc. Good for unstable drugs Example: antibiotics for reconstitution Granule Preparation Prepared by moistening blended powders and by passing this mass through a screen or a granulator. Granules are then air- or oven-dried. Flavors can be sprayed on the granules and then dried. Effervescent Granules Contain mixtures of citric acid, tartaric acid, or sodium biphosphate with a bicarbonate and a medicinal agent. The carbonated solution is a pleasant vehicle and lessens the bitter and salty taste of salts (e.g., magnesium sulfate). Effervescent Granules (cont.) Dispense in: – Packets – Wide-mouth bottles Do not want them to effervesce too quickly as they will overflow the container during mixing Examples: Lactinex, Bassoran, Zantac Effervescent Granulated Salts Fusion method- drugs and other solids are dissolved in an ointment base and then combined by melting the ingredient into the base Wet method- ingredients are moistened with a non- aqueous liquid to prepare a coherent mass which is then passed through a sieve and dried in an oven  MICROMERITICS The Science of Small Particles Particle Any unit of matter having defined physical dimensions Why Study Particles? 1. A majority of drug dosage forms are solids. 2. Solids are not “static” systems. 3. Physical state can be altered by physical manipulation. 4. They can alter therapeutic effectiveness. Measurement of Particle Size 1. Microscopic method 2. Sieving method 3. Sedimentation method 4. Elutriation method 5. Centrifugal method 6. Coulter counter 7. Permeation method 8. Adsorption method Micromeritic Properties 1. Solubility 2. Angle of repose 3. True density 4. Apparent density 5. Porosity 6. Void 7. True volume 8. Bulk volume 9. Bulkiness Porosity Void × 100 True Volume V Void Vbulk − V Vbulk Bulk Volume True volume + porosity Apparent Density Pa = Mass/bulk volume True Density P = Mass/true volume Bulkiness B = 1/Pa Packaging/Dispensing Oral administration – Wide-mouth containers – Powder papers Topical administration – Sifter containers – Puffer units Storage/Labeling Store in dry places. Protect from light in some cases. Keep out of reach of children. Stability Dry USP – 6 months if prepared from USP/NF ingredients – 25% of expiration date remaining if prepared from commercial product Patient Counseling Dose measuring technique? Mix with liquid or food? Premix and store? Quantity of powder to apply? Rub or pat into skin? Safe to apply where children are playing? Should the skin be dry? Sweaty? Powdered Dentifrice Triclosan 1g Ppt calcium carbonate 98 g Sodium lauryl sulfate 400 mg Saccharin sodium 200 mg Peppermint oil 0.4 mL Cinnamon oil 0.2 mL Wintergreen oil 0.8 mL Douche Powder Boric acid 80 g Ammonium aluminum sulfate 15 g Menthol 500 mg Sodium lauryl sulfate 500 mg Thymol 300 mg Phenol 200 mg Tannic acid 500 mg End of Discussion