POWDERS

1. POWDERS

2. Powders as a Dosage Form Powders are prepared either as dusting powders which are applied locally, dentifrices, products for reconstitution, insufflations and aerosols.

3. Advantages of Powders as a dosage form: • Flexibility in compounding and good chemical stability. • Disadvantages of powders as a dosage form: • Time-consuming to prepare • Not suited well for dispensing the unpleasant-tasting or • hygroscopic drugs. • Inaccuracy of dose for bulk powders. • The dose is influenced by many factors, including size of measuring spoon, density of powder, humidity, degree of settling and fluffiness due to agitation.  

4. Preparation of powder dosage forms Size reduction Reduction of particle size of all ingredients with the same range to prevent separation of large and small particles.

5. Trituration This term refers to the process of reducing substances to fine particles by rubbing them in a mortar with a pestle. This results in blending powders and breaking up soft aggregates of powders. When granular or crystalline materials are to be incorporated into a powdered product, these materials are triturated individually and then blended together in the mortar.

6. Pulverization by Intervention • This is the process of reducing the state of solids with the additional material as volatile solvents which can be removed easily after the pulverization has been completed and the powdered material is obtained. • This technique is applied to substances which are gummy and tend to reagglomerate or which resist grinding. • Example: • Camphor which cannot be pulverized easily by trituration because of its gummy properties, can be reduced to a fine powder by the addition of a small amount of alcohol or other volatile solvent. • Iodine crystals can be triturated with the aid of a small quantity of ether.

7. Levigation In this process a paste is first formed by the addition of a suitable non-solvent to the solid material. Particle-size reduction then is accomplished by robbing the paste in a mortar with a pestle. Levigation technique is used to incorporate solids into ointments and suspensions.

8. Blending (Mixing) Blending is used when two or more substances are to be combined to form a uniform powder mixture. Depending upon the nature of the ingredients and the amount of powder to be prepared mixing may be byspatulation, trituration, sifting, tumbling or by mechanical mixers.

9. Spatulation This method is used when small amounts of powders are to be blended by the movement of a spatula through the powders on a sheet of paper or an ointment slab.

10. Trituration • The method may be employed • both to reduce and mix powders. • Porcelain or Wedgewood mortar is • used. • For chemicals that may stain the • porcelain or Wedgewood surface, • a glass mortar may be preferred.

11. When potent substances are to be mixed with a large amount of diluent, geometric dilution method is employed to ensure the uniform distribution of the potent drug. By this method, the potent drug placed upon an equal volume the diluent in a mortar and the mixture is mixed by trituration. Then a second portion of diluent equal in volume to the powder mixture in the mortar is added, and the trituration is repeated. This process is continued by adding equal volumes of diluent to that powder present in the mortar and repeating the mixing until all of the diluent is incorporated.

12. Sifting Powders may also be mixed by passing them through sifters. This process results in a light fluffy product. This process is not acceptable for the incorporation of potent drugs into a diluent base.

13. Tumbling The powder enclosed in a large container which rotates generally by a motorized process. Such blenders are widely employed in industry to blend large amounts of powder.

14. Problems in powder manufacture The incorporation of volatile substances, eutectic mixtures, liquids and hygroscopic substances into powders presents problems that require special treatments.

15. Volatile Substances The loss of camphor, menthol and essential oils by volatilization when incorporated into powders may be prevented or retarded by use of heat-sealed plastic bags or by double wrapping with a waxed or glassine paper inside a bond paper.

16. Eutectic Mixtures Liquids result from the combination of phenol, camphor, menthol, thymol, antipyrne, phenacetin, acetanilid, aspirin, salol at ordinary temperatures. • These eutectic mixtures can be incorporated into powders by addition of an inert diluent or absorbent. • kaolin, starch, bentonite are used as absorbents • Incorporation of 20% silicic acid (particle size, 50 µm) prevented eutexia with aspirin, phenyl salicylate. This technique offers the advantage of extended product stability.

17. Magnesium carbonate or light magnesium oxide are used commonly as effective diluents for this purpose. An amount of diluent equal to the eutectic compounds is sufficient to prevent liquefaction for about 2 weeks. • Each eutectic compound should be mixed first with a portion of the diluent and gently blended together, preferably with a spatula on a sheet of paper.

18. Liquids • Liquids may be incorporated into divided powders. • Magnesium carbonate, starch or lactose may be added to increase the absorbability of the powders if necessary. • When the liquid is a solvent for a nonvolatile heat-stable compound, it may be evaporated gently on a water bath. • Lactosemay be added during the evaporation to increase • the rate of solvent loss by increasing the surface area. Some extracts and tinctures may be treated in this manner, although the use of an equivalent amount of a powdered extract is a more desirable technique.

19. Hygroscopic Substances • Substances that become moist because of affinity for • moisture in the air may be prepared as divided powders • by adding inert diluents. • Double-wrapping is desirable for further protection. • Extremely Hygroscopic compounds cannot be prepared • as powders.

20. Use and Packaging of Powders • Depending upon their use, powders are packaged and dispensed in two main ways: • Bulk powders. • Divided powders.

21. BULK POWDERS • Example of the bulk powders are: • Oral powders: as antacid and laxative powders, it can be taken by mixing an amount of powder in a portion of water or other beverage and swallowing as solution or suspension. • Douche powders: generally dissolved in warm water and used as antiseptics or cleansing agents for a body cavity as for vaginal use. Douche powders are Dispensed in wide-mouth glass jars serves to protect against air and moisture or loss of volatile materials

22. Dusting Powders: Medicated or non-medicated for external application for various parts of the body as lubricants, protectives, absorbents, antiseptics, astringents and antiperspirants agents. • Dusting Powders are usually dispensed in sifter • containers for convenient application to the skin. • Foot powders and talc powders are currently available • as aerosols. • Dentifrices: Dental cleansing powders, used in dental hygiene. • Denture powders, some used as dentifrices and others as adhesives to hold the dentures in place.

23. All powders should be stored in tightly closed containers • for Protection against humidity, air oxidation and loss of • volatile ingredients. • Dispensing powdered drugs in bulk amounts limited to • non-potent substances. • Powders containing potent substances or those that • should be administered in controlled dosage are • Supplied to the patient in divided amounts.

24. divided POWDERS • After the powder has been mixed, it may be divided into individual doses. • Each divided portion of powder may be placed on a small piece of paper or metal foil which is then folded or in small heat-sealed plastic bags so as to enclose the medication. • Hygroscopic and volatile drugs can be protected by using a waxed paper;

25. Powder Flow Properties • Pharmaceutical powders may be classified as free-flowing or cohesive (non-free-flowing). • Flow properties are significantly affected by changes in particle size, density, shape, electrostatic charge, and adsorbed moisture, which may arise from processing or formulation. • Preformulation, powder flow should be determined for the improvement of pharmaceutical formulation and consequences of processing. • This subject becomes vital for the development of a commercial solid dosage form containing a large percentage of cohesive material.

26. Factors affecting Powder Flowability: 1-Particle size: Frictional and cohesive forces (resistance to flow) are increased as the particle size is reduced . Very fine particles do not flow as large particles. In general, particles in the size range of 250-2000 µ flow freely if the shape is agreeable. Particles in the size range of 75-250 µ may flow freely or cause problems, depending on shape and other factors. With particles less than 100 µ in size, flow is a problem.

27. 2-Density and porosity: - Particles with high density and low porosity tend to posses free flowing properties. 3- Particle shape: Rough irregular particles presents more points of contact than smooth spherical particles thus Spherical particles flow better than needles. 4- Particle size distribution: Larger amount of fines can inhibit poor flowing. 5- Moisture content: Drying the powders will reduce the cohesiveness.

28. Flow rate determination • Powder flows through an orifice onto • an electronic balance. • Flow rate is determined by measuring weight of powder • pass through an orifice per time (g/sec). • Several flow rate determinations through a variety of • orifice sizes (1/8 to 1/2 inches) should be made. • In general, the greater the standard deviation between • multiple flow rate measurements, the greater is the • weight variation in products produced from that powder.

29. Particle Size Analysis The particles of pharmaceutical powders may be coarse to extremely fine. The USP utilizes terms which are related to the proportion of powder that is capable of passing through the openings of standardized sieves of varying dimensions in a specified time. Standard Sieve Shaker

30. Sieve Analysis Opening of Standard Sieves

31. Coarse powder -All particles pass through No. 20 sieve and not more 60% through No. 40 sieve. Moderately Coarse powder -All particles pass through No. 40 sieve an not more than 60% through No. 60 sieve Fine powder -All particles pass through No. 80 sieve. There is no limit as to greater fineness. Very Fine powder -All particles pass through No. 120 sieve. There is no limit as to greater fineness.

32. Methods for the determination of particle size: • Methods of particle size determinations include techniques that provide average particle size by: • Weight (sieve method, light scattering, sedimentation • method). • Volume (light scattering, electronic sensing zone, light • obstruction, air permeation and the optical • microscope).

33. Sieve Analysis Sieving:In which particles are passed by mechanical shaking through a series of sieves of known and successively smaller size and the determination of the proportion of powder passing through or being held on each sieve (range: from about 50 to 3360 micrometers, depending upon sieve sizes).

34. Microscopy:In which the particles are sized through the use of a calibrated network background (range: 0.2 to 100 micrometers)

35. Sedimentation : Particle size is determined by measuring the settling velocity of particles through a liquid medium in a gravitational or centrifugal environment. Sedimentation rate may be calculated from Stokes' law Using the "AndreasenPipet.“ The Andreasenpipet is designed where a sample can be removed from the lower portion at selected time intervals. The powder is dispersed in a nonsolvent in the AndreasenPipet. Agitated, and 20 mL samples removed over a period of time. Each 20 mL sample is dried and weighed.

36. Light energy diffraction: Particle size is determined by the reduction in light reaching the sensor when the particles, dispersed in a liquid or gas, passes through the sensing zone. Laser holography: in which a pulsed laser is fired through an aerosolized particle spray and photographed in three dimensions with a holographic camera,

37. Angles of Repose Ф The angle of repose is a relatively simple technique for estimating the flowability of a powder. Such measurements give at least a qualitative assessment of the internal cohesive and frictional effects under low levels of external loading, as might apply in powder mixing, or in tablet die or capsule shell filling operations.

38. The angle of reposecan be determined experimentally by allowing a powder to flow through a funnel and fall freely onto a surface. The height and diameter of the resulting cone is measured. It is the maximum angle that can be obtained between the free standing surface of a powder heap and the horizontal plane.

39. Tan Ф = Angle of repose Ф can be defined by the equation: Where: h is the height of the powder cone. D is the diameter of the powder cone. • Values of Ф between 20° - 40° indicate reasonable flow. • Powders with low angles of repose will flow freely • Above 50° the powder flows only with great difficulty.

40. Mass-Volume Relationships • The mass of a bulk powder can be accuracy determined • but measurement of the volume is more complicated. • The main problem arises in measuring the volume of • bulk powders is the presence of three types of air • spaces or voids between particles. • Open intraparticulate voids:- • Those within a single particle but open to the external • environment. • 2.Closed intraparticulate voids:- • Those within a single particle but closed to the external • environment. • 3. Interparticulate voids:- • The air spaces between individual particles.

41. Therefore, at least three interpretations of "powder volume may be proposed • The true volume (Vt): • The total volume of the solid particles, which excludes all • spaces greater than molecular dimensions, and which has • a characteristic value for each material. • The granular volume (particle volume)(Vg): • The cumulative volume occupied by the particles, • including all intraparticulate (but not interparticulate) • voids. • The bulk volume (Vbulk): • The total volume occupied by the entire powder mass • under the particular packing achieved during the meas

42. POROSITY, VOID AND BULK VOLUME • Packing and flow of powders are important for: • Impacting the size of container required for packaging • The flow of granulations • The efficiency of the filling apparatus during the tabletting • Encapsulating process. A number of characteristics can be used to describe powders including: • Porosity, true volume, bulk volume, apparent density, true density, and bulkiness.

43. The void is the space between the particles which resulting in a porosity. If particles are not uniform, the smaller particles will slip into the void spaces between the larger particles and decrease the void areas. The Void = Where: Bulk Volume, V bulk = The volume occupied by a selected weight of a powder. The True volume, Vt= The space occupied by the powder exclusive of spaces greater than the intramolecular space.

44. The Porosity= X 100 The bulk volume = True volume + Porosity

45. APPARENT DENSITY, TRUE DENSITY AND BULKINESS Bulk density is of great importance for capsule filling, tablet Compressibility and for the homogeneity of formulation in which there are large differences in drug and excipient densities. Apparent bulk density (g/ml) is determined by pouring presieved (40-mesh) bulk drug into a graduated cylinder via a large funnel and measuring the volume and weight "as is."

46. The Apparent Density Pa= The True Density P= The bulkiness, B = is the reciprocal of the apparent density B = 1 /pa Powders with low apparent density and large bulk volume are "light" powders, and those with high apparent density and small bulk volume are "heavy" powders.

47. Tapped density is determined by placing a graduated cylinder containing a known mass of drug or formulation on a mechanical tapper apparatus, which is operated for a fixed number of taps (≈1000) until the powder bed volume has reached a minimum. Using the weight of drug in the cylinder and this minimum volume, tapped density can be determined.

48. % Compressibility = X 100 Compressibility Where: Pt = The tapped bulk density P0= The initial bulk density

49. Compressibility index (I) = X 100 A simple indication of the flow property of a powder is given by using of compressibility index (I) Where: V = the volume occupied by a sample of the powder after tapping procedure Vo = the volume before tapping. Values of I below 15% usually give rise to good flow characteristics, but above 25% indicate poor flowability.