powders and graWRGVBDBUHURHGJRHGBnules.pptx

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1. Powders and granules

2. Outline Powders and granules Powders as a dosage forms Introduction (definition, classification & applications) Preparation (size reduction, mixing and packing) Challenges of powder dosage forms; eg , eutectic mixtures Granules as dosage forms Granulated preparations Effervescent granules and methods of preparations

3. Powders as a dosage forms The term “powder” has more than one implication in pharmacy. It may be used to describe The physical form of a material, that is, a dry substance composed of finely divided particles. Or, Type of pharmaceutical preparation A powder is defined as a dosage form composed of a solid or mixture of solids reduced to a finely divided state and intended for internal or external use

4. Advantages powdered and granulated products Solid preparations are more chemically stable than liquid ones. For example, the shelf-life of powders for antibiotic syrups, is 2-3 years, but once they are reconstituted with water it is 1-2 weeks 2. Powders and granules are a convenient form in which to dispense drugs with a large dose 3. Orally administered powders and granules of soluble medicaments have a faster dissolution rate than tablets or capsules because these must first disintegrate before the drug dissolves

5. Disadvantages powdered and granulated products 1 . Bulk powders or granules are far less convenient for the patient to carry than a small container of tablets or capsules are as inconvenient as liquid preparations 2. The masking of unpleasant tastes may be a problem with this type of preparation 3. are not suitable for administering potent drugs with a low dose. This is because individual doses are extracted from the bulk using a 5 mL spoon. 4. not a suitable for drugs which are inactivated in , or cause damage to the stomach

6. There are a variety of powdered dosage forms commercially available, such as bulk powders divided powders dusting powders insufflations, and dry powder inhalers.

7. Medicated Powders 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 Medicated powders for external use are dusted on the affected area from a sifter-type container or applied from a powder aerosol Medicated powders for oral use may be intended for local effects (e.g., laxatives) or systemic effects (e.g., analgesics) Sterile dry powders intended to be constituted with water or another suitable solvent prior to administration by injection

8. bulk powders The mixed ingredients are packed into a suitable bulk container, such as a wide-mouthed glass jar . The constituents of bulk powders are usually relatively non-potent and non-toxic medicaments with a large dose. Patients take this powder with a 5 ml spoon and dissolve it in water before use The major problem is the inaccuracy of dose Among the bulk powders available in prepackaged amounts are antacids ( e.g., sodium bicarbonate) and laxatives (e.g., psyllium ) Medicated powders for external application to the skin, usually topical anti- infectives (e.g., bacitracin zinc and polymyxin B sulfate) or antifungals (e.g., tolnaftate )

9. Divided Powders are bulk powders in which the individual dose has been packed separately modern packing methods are developed to replace the use of paper wrapping, such as foil and plastic laminates Effervescent powders can be packed into individual doses, because the plastic laminates can protect powders from moisture adsorption The powdered product should always be protected from exposure to moisture

10. Dusting Powders Dusting powders are designed for external use, acting as a therapeutic, lubricant, or protective act locally and are intended to have no systemic absorption are usually dispensed in a relatively fine state (micronized) to increase efficacy and decrease irritation Can be packed in glass or metal containers with a perforated lid to allow the powders to be dusted to the effective area

11. Excellent flowability is necessary for this dosage form Pressure aerosols are another delivery form that can generate dusting powders They are more expensive than the sifter-container but several advantages are realized, such as convenient operation, and protection from moisture, air, and contamination

12. Insufflations and Dry Powder Inhalers (Dpi) Insufflations are fine powders of drugs, which are dosed into the nose, ear, or throat by the use of an insufflator Pulmonary delivery of dry powder formulations is a popular approach to deliver the drug to the lung locally, for the treatment of such diseases as asthma and chronic obstructive pulmonary disease (COPD)

13. Preriparation Size reduction is the mechanical process of reducing the particle size of a substance to smaller pieces, to coarse particles, or to powder Various terms have been used synonymously with size reduction depending on the product, the equipment, and the process Crushing , Grinding, Milling, Pulverization and Dispersion The choice of equipment is determined by the properties of the solid powder, such as the initial particle size the desired size reached after size reduction

14. On a small scale, the pharmacist reduces the size of chemical substances by grinding with a mortar and pestle . A finer grinding action is accomplished by using a mortar with a rough surface (as a porcelain mortar) than one with a smooth surface (as a glass mortar). Grinding a drug in a mortar to reduce its particle size is termed trituration or comminution . Pulverization is the process in which a volatile solvent is added during trituration of solids to reduce its particle size. For example Camphor, which cannot be pulverized easily by trituration because of its sticky properties; however, on the addition of a small amount of alcohol or other volatile solvent, this compound can be reduced readily to a fine powder because when the solvent is permitted to evaporate a fine powdered material is formed.

15. Levigation is the process in which a non-solvent ( the levigating agent) is added to solid material to form a paste, and particle-size reduction then is accomplished by rubbing the paste in a mortar with a pestle or on an ointment slab using a spatula. On a large scale various types of mills and pulverizers may be used to reduce particle size It has been proposed that less than 2% of the total mechanical energy is effective on the size reduction process .

16. The purpose of comminution includes: Reduction of drug particle size, increasing surface area, improve bioavailability. Alteration of powder flow, improve mixing efficiency of different drugs & reduce powder irritation propensity. Acceleration of dissolution rate of powder. Facilitate formulation of powder into various dosage forms, such as suspensions, tablets, and capsules

17. Mixing When two or more powdered substances are to be combined to form a uniform mixture it is best to reduce the particle size of each powder individually before weighing and blending. Depending on the nature of the ingredients, the amount of powder, and the equipment , powders may be blended by Spatulation trituration sifting , and tumbling

18. A- Spatulation Spatulation is blending small amounts of powders by movement of a spatula through them on a sheet of paper or an ointment tile. Because homogeneous blending is not as certain as other methods this method is not suitable for Large quantities of powders or Powders containing potent substances. Very little compression or compacting of the powder results from spatulation , so it is suited to mixing solid substances that form eutectic mixtures.

19. Eutectic mixtures are solids when in close and prolonged contact with one another liquefy. Substances that form eutectic mixtures when combined include Phenol Camphor Menthol Thymol aspirin, To diminish contact, a powder prepared from such substances is commonly mixed in the presence of an inert diluent , such as light magnesium oxide or magnesium carbonate, to separate physically the troublesome agents.

20. B- Trituration Trituration may be employed both to comminute and to mix powders. If simple admixture is desired without special need for comminution , the glass mortar is usually preferred. 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. Geometric method is especially indicated when the potent and other ingredients are the same colour and a visible sign of mixing is lacking.

21. Tumbling mixer It involves tumbling the powder in a rotating chamber. Special small-scale and large-scale motorized powder blenders mix powders by tumbling them Mixing by this process is thorough but time consuming. are likely to mix powders with good flowability and granules, rather than cohesive or powders with poor flowability because shear force provided by these mixers is not enough to separate the individual particles from agglomerates are most commonly used for powders with similar densities. FIGURE Laboratory-scale Triple V-type blender

22. Segregation is an undesirable separation of the different components of the blend . Segregation happens during or after mixing due to handling or pouring. is very important in pharmaceutical preparations as it causes a non random mixing Effects of segregation Increased content variation Un acceptable variation in weight Processing difficulties Non uniform drug release rate

23. Causes of powder segregation Particle size effect It is the main cause of segregation Particle –density effect If component are of different density, the more dense materials will have a tendency to move downward even if the particles size are similar Particle shape Spherical particles exhibit the greatest flow ability and are therefore more easily mixed, but they also segregate more easily than non spherical particles

24. Mechanism of segregation Percolation segregation Smaller particles tend to fall through the void between larger ones and moves to the bottom of the mass. Example - during vibration, Stirring or poring b. Trajectory segregation During mixing larger particles will tend to have greater kinetic energy imparted to them and therefore will tend to move greater distance than smaller particles before come to rest

25. Elutriation segregatio /Dusting out / When a material is discharged from a container, very small particles dust in a mix may tend to be blown upward by turbulent air current as the mass tumbles and remains suspended in the air

26. General guidelines to minimize or prevent segregation include Selection of particle size fractions E.g. sieving to remove fins or lumps to achieve drug and excipients within narrow particles size distribution range Selection of excipients which have densities similar to the API minimum number of transfer steps and drop heights; control of dust generation; control of fluidization of the powder slow fill/transfer rate proper hopper design so that powder residence time is minimized

27. Packing The powder mixture is packaged according to its use Bulk oral powders can be packaged in glass, plastic, metal, or other containers that have a wide mouth to allow use of the powder measure . Divided powders, or powder papers, must be individually folded Topical powders can be poured into sifter top containers or powder shakers, and insufflations can be filled into plastic puffer units

28. Challenges of powder dosage forms Eutectics Some powders may become sticky or pasty, or they may liquefy when mixed together Substances that form eutectic mixtures when combined include phenol, camphor, menthol, thymol , aspirin, phenyl salicylate , and other similar chemicals. To diminish contact, a powder prepared from such substances is commonly mixed in the presence of an inert diluent , such as light magnesium oxide or magnesium carbonate, to separate physically the troublesome agents

29. Hygroscopic and Deliquescent Powders Hygroscopic powders are those substance which will absorb moisture from the atmosphere. Eg . Phenobaribital sodium , potassium citrate Deliquescent powders are those substance which will absorb moisture from the air to the extent that they will partially or wholly liquefy Eg . Calcium chloride ,potassium acetete These problems overcome by Dispensing the ingredients in tight containers and incorporate a desiccant packet or capsule when necessary dilute the powder with an inert drying powder to reduce the amount of surface area exposed to the moisture

30. Table Common Hygroscopic & Deliquescent Powders Ammonium bromide Ammonium chloride Ammonium iodide Calcium bromide Calcium chloride Ephedrine sulfate Hyoscyamine hydrobromide Hyoscyamine sulfate Iron and ammonium citrate Lithium bromide Pepsin Phenobarbital sodium Physostigmine hydrobromide Physostigmine hydrochloride Physostigmine sulfate Pilocarpine alkaloid Potassium acetate Potassium citrate Sodium bromide Sodium iodide Sodium nitrate Zinc chloride

31. Efflorescent Powders An efflorescent powder is a crystalline powder that spontaneously liberate some or all of their water of crystallization, either during manipulations or on exposure to a low-humidity environment If this occurs , the powder will become sticky and pasty , or it may even liquefy . One approach to solve problem to use an anhydrous salt form of the drug (preferable) keeping in mind the potency differential between its anhydrous form and its hydrated Addition of an inert sorbent powder and to use a light, noncompacting method of mixing the powders.

32. Table Common Efflorescent Powders Alums Atropine sulfate Caffeine Calcium lactate Citric acid Cocaine Codeine Codeine phosphate Codeine sulfate Ferrous sulfate Morphine acetate Ferrous sulfate Morphine acetate Quinine bisulfate Quinine hydrobromide Quinine hydrochloride Scopolamine hydrobromide Sodium acetate Sodium carbonate ( decahydrate ) Sodium phosphate Strychnine sulfate Terpin hydrate

33. Granules a dosage form composed of dry aggregates of powder particles that may contain one or more APIs, with or without other ingredients flow well compared to powders T hus, granulations are commonly used in tablet making to facilitate the free flow of material from the feeding container (or hopper) into the tablet presses are usually more stable to the effects of atmospheric humidity and are less likely to cake or harden upon standing. Because their less specific surface area than powder , Granules also are more easily wetted by liquids than are certain light and fluffy powders (which tend to float on the surface) and are often preferred for dry products intended to be constituted into solutions or suspensions

34. Granules are prepared by wet and dry methods . One basic wet method is to moisten the powder or powder mixture and then 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.

35. 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 The dosage form is dissolved or dispersed in water to initiate the effervescence prior to ingestion The resulting carbonated solution masks undesirable taste of any medicinal agent . When tartaric acid is used as the sole acid, the resulting granules readily lose their firmness and crumble . Citric acid alone results in a sticky mixture difficult to granulate.

36. Effervescent granules are prepared by two general methods: ( a) the dry or fusion method and ( b) the wet method.

37. Dry or Fusion Method In this method, the one molecule of water present in each molecule of citric acid acts as the binding agent for the powder mixture the citric acid crystals are powdered and then mixed with the other powders of the same sieve size to ensure uniformity of the mixture The mixing of the powders is performed as rapidly as is practical, preferably in an environment of low humidity to avoid absorption of moisture and a premature chemical reaction.

38. After mixing, the powder is placed on a suitable dish in an oven at 34°C to 40°C. During the heating process, an acid resistant spatula is used to turn the powder The heat releases the water of crystallization from the citric acid, which, in turn, dissolves a portion of the powder mixture, setting the chemical reaction and consequently releasing some carbon dioxide

39. This causes the softened mass of powder to become somewhat spongy when it has reached the proper consistency (as bread dough), it is removed from the oven and rubbed through a sieve to produce granules of the desired size The granules are dried at a temperature no exceeding 54°C and are immediately placed in containers and tightly sealed.

40. 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 the pliable mass for granulation. In this method, all of the powders may be anhydrous as long as water is added to the moistening liquid Just enough liquid is added (in portions) to prepare a mass of proper consistency; then the granules are prepared and dried

41. Quality control Bulk Powders The pharmacist should compare the final weight of the preparation with the theoretical weight . The powder should be examined for uniformity of color particle size flowability,and freedom from caking . Divided Powders For divided powders, the pharmacist should individually weigh the divided papers and then compare that weight with the theoretical weight . The packets should be checked to confirm uniformity