Powders and granules

topic about powders and granules as pharmaceutical agents,methods of granulation,types of powders,

1. Introduction to Pharmaceutics-1 PCT 221 3rd Semester ) 8/13/2015 1 IHS-Gaborone

2. Unit-1 Powders and Granules Unit-2 Semisolid Dosage Forms Unit-3 Emulsions Unit-4 Suspensions Unit-5 Pharmaceutical Calculations Total Credit = 3 Assessment = 2CAs (60%) + End of sem. Exam (40%) 8/13/2015 2 IHS-Gaborone

3. Recommended Books Pharmaceutical dosage forms and drug delivery systems Ansel H.C, Popovich Pharmaceutics, The science of dosage form design, M.E Aulton Remington, The science and practice of Pharmacy Vol-1 & 2 Pharmaceutical Calculations by Stocklosa & Ansel Any other handouts / Reference material given to the class 8/13/2015 3 IHS-Gaborone

4. Unit-1 Powders and Granules 8/13/2015 4 IHS-Gaborone

5. Unit contents Powders and granules as dosage forms Special problems in powdered dosage forms Factors affecting drug availability from powdered dosage forms Package and storage of powders 8/13/2015 5 IHS-Gaborone

6. TOCs Basic definitions Advantages and disadvantages Powders and granules as dosage forms (types / Differences) Special problems in powdered dosage forms / Solution Factors affecting drug availability from Powdered DF Packaging and storage Particle size and size analysis Calculations 8/13/2015 6 IHS-Gaborone

7. Definitions Micromeritics: Science of small particles Powders: Is a mixture of finely divided drugs and /or Chemicals in a dry form According to B.P = subdivided solids containing constituent particles which can range 1.25um – 1.7mm in diameter As DF = are formulations in which powdered drug has been mixed with powdered excipients to produce final formulations Eg . Oral powders, Dusting, dentifrices, bulk powders etc 8/13/2015 7 IHS-Gaborone

8. Granules (Sieve size=4-12) Are aggregations of fine particles of powders in a mass of about spherical shape or Consists of powdered particles which have been aggregated to form a larger particles of about 2-4mm in diameter Can be prepared by Dry or Wet Granulation techniques 8/13/2015 8 IHS-Gaborone

9. Why we prepare granules when we have powders? To avoid powder segregation, if the powder is composed of particles with different dimensions & different densities, a separation between these particles will occur. To enhance the flow of powder, Higher flow ability gives better filling of the dies or containers, during a volumetric dosage. 8/13/2015 9 IHS-Gaborone

10. Granules have higher porosity than powders, To improve the compressibility of powders. The granulation of toxic materials will reduce the hazard of generation of toxic dust, which may arise during the handling of the powders. Materials, which are slightly hygroscope, may adhere & form a cake if stored as a powder. 8/13/2015 10 IHS-Gaborone

11. Sieve Number A number used to designate the size of the Sieve, which corresponds to the no. of openings per linear inch E.g.. Sieve 20 will have 20 openings in 1 linear inch Sieve opening Its an approximate size of aperture of a given sieve as given in USP E.g. sieve no 20 will have 20 opening per linear inch and each opening will have an aperture size = 850µm 8/13/2015 11 IHS-Gaborone

12. Some commonly used sieve no Sieve Number Sieve opening (µm) 20 850 40 425 60 250 80 180 120 125 . . .. .. … … 400 38 8/13/2015 12 IHS-Gaborone

13. Angle of repose ( θ = Tan -1 h/r) The maximum slope measured in degrees from the horizon at which loose solid material will remain in place or Angle of repose of a granular powder is the steepest angle of descent or dip relative to horizontal plan to which a material can be piled up. If θ > 50 unsatisfactory flow θ = 25 or less than 25 very good flow properties 8/13/2015 13 IHS-Gaborone

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15. Glidents Excipients that increase flow properties of given material By correcting surface irregularity, reducing friction or by neutralizing surface charges b/w particles E.g., Mag. Stearate, Aerosil (colloidal silicon dioxide), Starch, Talc 8/13/2015 15 IHS-Gaborone

16. Geometric mixing/dilution (doubling up method) Mixing of ingredients according to order of their increasing weight/volume in equal proportions E.g. Consider the following master formula A =10g B =50g C =40g D =90g What could be the benefits ? 8/13/2015 16 IHS-Gaborone

17. Powder mixing techniques Spatulation is the combining of materials (2 or more powders) into a homogeneous mixture by continuously mixing them together & smoothing the mass out on a smooth surface with a spatula Trituration is the process for reducing the particle size of a substance by grinding, eg grinding of powders in a mortar with a pestle Sifting relates to putting through a sieve or straining device to separate fine particles from coarse ones Tumbling 8/13/2015 IHS-Gaborone 17

18. Advantage of powders/granules Stability Solid are more stable than liquids E.g. ( Ampicillin ) Antibiotics powders dry form = 2-3 yrs shelf life While liquid of same antibiotics = 1-2 weeks More suitable/convenient DF for large dose E.g. Mag.Trisillicate Antacid (1-5g) 8/13/2015 18 IHS-Gaborone

19. 3. Faster dissolution rate/Bioavailability Increase S.A -------  increase dissolution Rapid onset of action 4. Can be taken orally by some patients who are unable to swallow other solid dosage forms such as capsules and tablets 8/13/2015 19 IHS-Gaborone

20. Disadvantages Inconvenient to carry / handle (except when presented as divided DF) Unpleasant Taste Not very suitable DDS for potent drugs Divided DF can be used however Tabs are preferred Not suitable for acid labile / Enzyme prone drugs (Coated granules may be used) 8/13/2015 20 IHS-Gaborone

21. Disadvantages……. (Cont.) Poor/Misunderstanding about correct method of use Higher decomposition rate incase of Hygroscopic, deliquescent or aromatic ingredients Because of different particle size/density diff. powder mix can be partly separated. Non uniform distribution 8/13/2015 21 IHS-Gaborone

22. Powders VS Granules Powders Granules Comparatively poor flow properties Flow well compared to tablets, good choice for compressing tabs Relatively less stable (physically and Chemically) due to inc. S.A & Atm. Effect Has less surface area, more stable to atm. effect More likely to hardening / cake formation on long storage Less likely For some powders, drugs float on the surface, difficult to make solution More easily wetted by the solvents , good choice reconstitution liquids Relatively poor compressibility Good compressibility Chances of non uniform dosing are more Relatively more uniformity of contents in case of granules More dust due to small p.s Generate less dust on handling Comparatively less appealing Have a more elegant appearance Relatively simple method of processing/formulation It involves more processing, exposure to heat and contact with solvents 8/13/2015 22 IHS-Gaborone

23. Preparation of Granules Wet method Moistening the desired powder Passing paste like mass thru sieve no 4-14. Tray dry / oven dry / vacuum dry Packed and labeled 8/13/2015 IHS-Gaborone 23

24. Dry method Powder material is passed through a roll compactor Granulating machine. Densified sheets or flakes The compacted powder is then granulated to uniform particle size by passing through a mechanical granulator. 8/13/2015 IHS-Gaborone 24

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26. Powders and granules as dosage form. 8/13/2015 26 IHS-Gaborone

27. Powders / Granules Therapeutic use: As a true & proper pharmaceutical dosage form Non therapeutic use: for the preparation of other dosage forms Tablets, Capsules, Suspensions, Solutions etc Bulk/divided/dusting/insufflations/DPI/Reconstitution All powders are stored at dry place Away from children 8/13/2015 27 IHS-Gaborone

28. Bulk Powders Mixed ingredients are packed suitable containers like wide mouthed bottles or glass jars Constituents are non toxic / Less potent Large doses can be dispensed Usually supplied with a measuring spoon Proper directions for use should be provided 8/13/2015 28 IHS-Gaborone

29. Bulk Powders (Cont…) E.g. Compound Mag Trisilicate powder Refreshens salt (laxative) Douch powders for vaginal irrigation/ cleansing Dietry suppliments and feeding formula. STORAGE: wide mouthed bottles, plastic / glass, Cool and dry place, out of children reach Prepare a list of at least 3 bulk powders available in Botswana, Ingredients, Uses, type of packaging etc. 8/13/2015 29 IHS-Gaborone

30. Bulk Powders (Cont…) 8/13/2015 30 IHS-Gaborone

31. Divided powders More potent ingredients are usually packed individually/ separately wrapped. List advantages / Disadvantages E.g. Mag. Trisilicate powder individually wrapped Grand Pa , (?) Acetyl cystine List some more with ingredients (check Community Pharmacy) 8/13/2015 31 IHS-Gaborone

32. Divided powders (Cont…) Packaging Ind. Wrapped paper, (How to wrap) If material is volatile or moisture sensitive than wax lined paper or grease proof paper Air tight sealed sachets Foiled laminate (replaced Paper) Individual powder are than boxed. (easy handling) Storage Cool and dry place, Avoid moisture (avoids agglomerates formation) 8/13/2015 32 IHS-Gaborone

33. Divided powders (Cont…) 8/13/2015 33 IHS-Gaborone

34. Dusting Powders. Used externally for Therapeutic ---- antifungal Prophylaxis----- antifungal/antiseptic Lubricating------ talc, Kaolin etc Dusting powders for open wounds should be sterile ( chlorohexidine Dusting Powders) , but lubricating powders do not need to be sterilized, however should be free from pathogens/Spores, Dry heat for sterilization is usually used,, (160 C for more than 60 minute) 8/13/2015 34 IHS-Gaborone

35. Dusting Powders.(Cont…) Packaging, Plastic, Glass or metal drum fitted with a perforated lid. Glidents are usually added to enhance the flow (Talc, Sterillizable Maiz starch) Storage: Closed Lid, Dry place, Away from child….. Examples Antifungal/ Antibacterial foot powders. Zinc undecylinate , Chlorohexidine Lubricating dusting powder, Talc 8/13/2015 35 IHS-Gaborone

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37. Insufflations Are medicated powders intended to be blown into regions such as ear, nose, and throat with the help of an insufflators Not very acceptable, In- elegent and less convenient to use, May show systemic effects (Rapid abosrption ) Some drugs are more rapidly absorbed from lungs than oral use. E.g. Sodium Chromoglycolate Traditional insufflator replaced by Advance devices, Handihaler , Accuhaler , Etc. 8/13/2015 37 IHS-Gaborone

38. Dry powders for inhalation (DPIs) DPIs are used to deliver medicaments to lungs in a dry powder form using a hand-held device, as you inhale through it. It does not have propellant like MDI do. E.G Seretide Accuhaler , (Can you list what does serretide contains) Handihaler Uses a capsule in device which is broken down as you operate and than u inhale medicaments. 8/13/2015 38 IHS-Gaborone

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41. FDA approved Afrezza (Insulin DPI) 8/13/2015 IHS-Gaborone 41

42. Video Demonstration 8/13/2015 IHS-Gaborone 42

43. For optimum delivery and absorption into the lungs,,,,,,,, What should be the Particle size ???? 8/13/2015 43 IHS-Gaborone

44. 8/13/2015 IHS-Gaborone 44 If particle size is less than 0.5 micron, than drug may be exhaled out with breath when given as powdered DF…...

45. Oral antibiotics powders Reconstituted at the time of use. Moisture can cause degradation of the product, So presented as dry powder for reconstitution E.g. Phenoxy methyl peicillin . Cefaclor , Augmentin List more Shake well before use for suspension 8/13/2015 45 IHS-Gaborone

46. Powder for injections (PFI) Sterile powders in ampoule / Vials Must be made immediately before use Diluents WFI Contains other additives along with active moiety E.g. Augmenting PFI Amphoteracin B, Ampicillin , Ceftriaxone PFI Cephradine , and chloramphenical PFI 8/13/2015 46 IHS-Gaborone

47. Special problems in Powdered DF / Solution 8/13/2015 47 IHS-Gaborone

48. Volatile substances Such as Camphor, menthol, essential oils Evaporation loss. Solution Packed into heat sealed plastic bags, Air tight containers Proper storage instructions to the client 8/13/2015 IHS-Gaborone 48

49. Eutectic mixture Some solids when mixed together form liquid. E.e . Phenol, menthol, thymol , antipyrene , phenacetin . Solution. Adding inert diluents such as Mag. Carbonate Light Mag oxide Kaoline , Starch, Bentonite 8/13/2015 IHS-Gaborone 49

50. Liquids Can be added in small amounts to powders. Some adsorbing materials should be added. Lactose, Mag.Carbonate , Starch. Fluid extract & Tinctures used in this way 8/13/2015 IHS-Gaborone 50

51. Hygroscopic or Deliquescent material Absorb moisture from air and liquefy Increase rate of hydrolysis Packed in air tight containers. Inert diluents can be added. 8/13/2015 IHS-Gaborone 51

52. Efflorescent materials Crystalline substances may liberate water of crystallization due to trituration and powder becomes wet. Anhydrous salt form can be used. Inert diluents can be added. 8/13/2015 IHS-Gaborone 52

53. Factors affecting Drug availability from Powdered DF 8/13/2015 IHS-Gaborone 53

54. Some basic concepts 8/13/2015 IHS-Gaborone 54

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57. Particle size can influence a number a factors Dissolution rate Suspendability Uniform distribution Penetrability Texture of the formulation 8/13/2015 IHS-Gaborone 57

58. Dissolution Process by which a drug particle dissolves 8/13/2015 IHS-Gaborone 58 Noyes Whiteny Equation

59. Surface area Particle size is inversely related to S.A Poorly or slowly soluble drugs when presented in small particle size…… enhanced dissolution…… enhanced bioavailability E.g. Theophyllin , Griseofulvin Micronized powder in SDF show more rapid absorption 8/13/2015 IHS-Gaborone 59

60. Crystal or amorphous form Amorphous form of a chemical is more soluble than its crystalline counterpart. E.g. Chloramphenicol is ineffective in its crystalline form but show good absorption through GIT in its amorphous state 8/13/2015 IHS-Gaborone 60

61. Salt form Drugs are either week acid or week basis. E.g. EthyleneDiAmine salt of Theophyyline has 5-Fold water solubility 8/13/2015 IHS-Gaborone 61 Sodium and potassium salts of week organic acids & Hydrochloric salts of week organic basis SHOW Rapid dissolution rate than respective free drugs

62. Sate of hydration Anhydrous form of an organic molecule is more soluble than its hydrated counter part. E.g. Ampicillin Anhydrous is more soluble than its tri-hydrate form 8/13/2015 IHS-Gaborone 62

63. Effect of pH Unionized form of drug absorb more faster than ionized form. Week acidic drugs absorb well in acidic pH. i.e Stomach Basic drugs absorb well in intestine. 8/13/2015 IHS-Gaborone 63

64. Particle size and Size distribution analysis 8/13/2015 IHS-Gaborone 64

65. Particle size and Size distribution analysis A number of methods can be used including Microscopy Calibrated grid background Sieving Sedimentation rate Terminal settling velocity Light energy diffraction Reduction of light reaching the sensor Laser holography 3 D picture by holography camera Cascade impact Striking surface with air stream 8/13/2015 IHS-Gaborone 65

66. Sieving technique Sieve number ? Sieve Opening ? Principle Particles passed by mechanical shaking through a series of sieves of known sizes (which reduces gradually from top to bottom), Amount of powder retained / Passed through is determined and manipulated 8/13/2015 IHS-Gaborone 66

67. Sieves are usually made up of wired cloth woven from Brass, Bronze or other metals 8/13/2015 IHS-Gaborone 67 Sieve No. Sie ve Opening (µm) 20 850 40 425 60 250 80 180 120 125 ….. …. 400 38

68. USP characterize Powders by following descriptive terms 8/13/2015 IHS-Gaborone 68 Type of powder All particles pass thru Sieve No Not more than Very coarse 8 20% thru 60 Coarse 20 40% thru 60 Moderately coarse 40 40%thru 80 Fine 60 40% thru 100 Very fine 100 No limit

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70. Powders calculations 8/13/2015 IHS-Gaborone 70

71. While dealing powders calculations Always calculate for at least 1 extra powder to compensate loss of powder during manipulations If amount of active ingredient is less than minimum weighable qty than dilutions (triturations) are to be made Min. weighable qty is diluted over several time to obtain req. dose 8/13/2015 IHS-Gaborone 71

72. Doubling up method / Trituration Calculations involving powder volumes 8/13/2015 IHS-Gaborone 72

73. E.g. Rx Hyoscine HBr 300 mcg mitte 4 powders one to given 30minutes before journey (Remember: minimum powder weight for divided powder = 120mg) Calculate for 5 doses Active req. = ? Diluent (lactose) req. = ? 8/13/2015 IHS-Gaborone 73

74. Step-1 Hyoscine HBr =100mg Diluent =900mg Step-2 Triturate A =100mg Diluent =900mg Step-3 Triturate B =? Diluent =? 8/13/2015 IHS-Gaborone 74

75. Example Rx Send 10 aspirin powders 200mg for a child of 3-years (14kg) Is dilution required? 300 mg tabs are available in dispensary 8/13/2015 IHS-Gaborone 75

76. Example Calculate quantities required to make 8 powders each containing 200mcg of digoxin per 120 mg of powder. Use lactose as a diluents Min. weighable qty = 100mg (class B balance) 8/13/2015 IHS-Gaborone 76

77. Calculation involving powders volume Powder displacement Example Calculate the volume of suspension occupied by amoxicillin powder 150mL – 111mL = 39mL 8/13/2015 IHS-Gaborone 77

78. Quantity of amoxicillin present in entire bottle 5mL contains =250mg 150mL contains =7500mg Volume of suspension that will contains 500mg/5mL 7500mg /500mg/5mL =75mL Volume of purified water required 75mL-39mL =36mL of water to be added. 8/13/2015 IHS-Gaborone 78

79. If the volume of 250mg of ceftriaxone sodium (powdered) is 0.1mL. How many mL of diluents should be added to 500mg of ceftriaxone to make 250mg / mL concentrated suspension. Volume of ceftriaxone ? Final volume of product.? Volume to be added.? 8/13/2015 IHS-Gaborone 79

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81. Some practice problems 8/13/2015 IHS-Gaborone 81

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