1. PH 201.631 Suppositions and pessasies Are semisolid dosage forms meant for Insertion into body cavities. Formulated to melt at body temperature. Introduction

2. PH 201.632 Used to treat local conditions such as hemorrhoids in rectum, infections in vagina Useful in infants, debilitated patients, nausea, vomiting, incapability of swallowing and GIT disturbances Merits :

3. PH 201.633 For prolonged action of drugs Faster onset & action than oral administration Degradation at gastric P H is avoided

4. PH 201.634 Should be stored at freezed conditions Inconvenient to patients. Demerits :

5. PH 201.635 FIG.NO.1: SHAPES AND SIZES OF SUPPOSITORIES

6. PH 201.636 Types of suppositories Rectal suppositories : For introduction into the rectum For systemic action Vaginal suppositories : Meant for introduction into vagina med for local action Nasal suppositories : Meant for introduction into the nasal cavity Also known as nasal bougies

7. PH 201.637 Urethral suppositories : For introduction into urethra Ear cones : For introduction into the ear

8. PH 201.638 New trends of suppositories : 1.Tablet suppositories Prepared by compression 2.Layered suppositories Contain different drugs in different layers

9. PH 201.639 3.Capsule suppositions Soft gelatin capsules & different shapes and sizes are used 4.Coated suppositions Coated by dipping in solution of coated materials

10. PH 201.6310 5.Disposable suppositions: Suppository material is poured into the disposable moulds and cooled.

11. PH 201.6411 Suppository base exert influence on the action of the drug Ideal properties of base are : Should melt at body temperature Should keep its shape Should release the medicament readily Should be non-t0xic,non-irritant to the mucous membrane Suppository Bases

12. PH 201.6412 Should be stable an storage Should be compatible with large number of drugs Should be stable it heated above its melting point Should be easily moulded Should have wetting and emulsifying properties.

13. PH 201.6413 Oleaginous bases Water soluble bases Water miscible bases Emulsifying bases Types & Suppositories bases

14. PH 201.6414 Theobroma oil Yellowish white solid Obtained from crushed and roasted seeds of theobroma cocoa Known as coca butter M.P-30-35 0 c Mixture & glyceryl esters of Stearic acid Oleic acid and Palmitic acid Oleaginous Bases

15. PH 201.6415 Shows phenomena of polymorphism When melted and cooled get solidified into different crystalline forms depending upon melting temperature rate & cooling,size & the mass. Becomes rancid and melts in warm weather Disadvantages

16. PH 201.6416 Sticks to the sides of the mould Leakage from body cavities Immiscible with body fluids Liquefy when combined with drugs like chloral hydrate

17. PH 201.6417 Used when large quantities of aqueous solutions are to be incorporated 5% glycerol momostearate 10% lanette wax 2-3% cetyl alcohol 4% bees wax 12% spermaceti Emulsified Theobrama oil

18. PH 201.6418 Obtained by hydrogenation of vegetable oils like Arachis oil Cotton seed oil Coconut oil Palm oil Hydrogenated oils Used as a substitute for theobroma oil

19. PH 201.6419 These are Resistant to oxidation Lubrication & mould is not required Over heating does not affect the solidifying point Produce colorless, odour less elegant suppositories Good emulsifying and water capacities

20. PH 201.6420 Disadvantages : Become brittle on rapid cooling More fluid than theobroma – when melted

21. PH 201.6521 Aqueous bases are water soluble and water miscible bases They are three types : Glycero-gelation bases Macrogol bases Soap glycerin bases

22. PH 201.6522 Mixture of glycerol and water with gelatin Suitable for suppositories and pessaries Glycerogelatin Bases

23. PH 201.6523 Glycerogelation base B.P. contains 14%w/w gelatin, 70% glycerol and rest water USP. base contains 20%w/w gelatin 70% glycerol and rest water

24. PH 201.6524 Dissolves in body secretions Provides prolonged release slower to soften, mix with physiologic fluids Advantages

25. PH 201.6525 Difficult to prepare and handle Solution depends an the content and quality of gelatin Gelatin is gyroscopic, requires cold storage Disadvantages

26. PH 201.6526 Gelatin is incompatible with drugs like tannic acid, Gallic acid and ferric chloride More changes of bacterial and mould growth preservative is required Has physiological action as laxative

27. PH 201.6527 Gelatin is replaced with sodium stearate Soap helps in the evacuation action of glycerin Soap – glycerin suppositories

28. PH 201.6528 Hygroscopic Must be protected from atmosphere Disadvantages

29. PH 201.6529 PEG`s are commonly known as carbowaxes or polyglycols or macrogols Physical character changes according to molecular weight Macrogols < 1000 are liquids Macrogols > 1000 are solids Polyethylene glycols : (PEG)

30. PH 201.6530 Chemically stable Non – irritant Do not allow bacterial or mould growth Physiologically inert Provide prolonged action Do not stick to the mould Have smooth and clean appearance Advantages

31. PH 201.6531 Hygroscopic – require special storage condition Incompatible with drugs like tannins, phenols Disadvantages

32. PH 201.6532 Synthetic bases Witepsol : Consists of triglycerides of saturated vegetable acid and partial Estes Small amount of bees wax is added in hot climates Suppositories should be cooled quickly mould should be lubricated Emulsifying bases

33. PH 201.6533 Mixture of mono, di and triglycerides of saturated fatty acids also known as adeps solidus White, brittle, odorless Tasteless solid Massa Esterinum

34. PH 201.6534 M.p -33.5 to 35.5 Available in various grades Grade B is commonly used in dispensing

35. PH 201.6535 Consists of glyceryl esters of Lauric acid Small amount of glycerol monostearate to improve water absorbing capacity Massuppol

36. PH 201.6536 Does not alter the physical characteristics Solidify rapidly, Non-irritant Lubrication is not required Can absorb fairly large amount of water on aqueous liquid White, odorless,clean and attractive Less liable to rancidity Advantages

37. PH 201.6537 Should not be cooled rapidly Not very viscous on melting Medicaments settle down rapidly Disadvantages

38. PH 201.6638 Suppositories are prepared by  Rolling method  Hot process or fusion method  Cold compression

39. PH 201.6639 Ancient Method  Base is rolled into desired shapes with hand  Method is not used now a days Rolling Method

40. PH 201.6640 Hot Process Or Fusion Method  Used for dispensing purposes  Base is melted and medicament is incorporated  Filled in lubricated mould  Cooled and removed

41. PH 201.6641 Suppository Mould

42. PH 201.6642 Suppository moulder

43. PH 201.6643 Moulds In dispensing  of various types and sizes are available  Suppository mould having 6-12 cavities with desired shape and size  Made of stainless steel, nickel, copper,alloy, brass aluminum and plastic

44. PH 201.6644  Mould is opened longitudinally by removing screws  Cleaned by immersing in hot water containing detergent  Rinsed thoroughly  Wiped gently with soft cloth, then dried  Lubricated if necessary Cleaning

45. PH 201.6645 Lubrication Of Mould  Essential for cocoa bitter base glycerol gelatin base  Lubricant used for Cocoa butter  Soft soap  Glycerin  Alcohol 90%  Glycero- gelatin  Liquid paraffin or arachis oil  Emulsifying base  No lubricant is used

46. PH 201.6646  Lubricant is applied with a brush or gauze swab  Do not use cotton (fibers detach easily)  Drain excessive lubricant by keeping the mould in inverted position on ice

47. PH 201.6647 Calibration of the mould  Size remains the same, Weight varies  Densities of bases and medicaments are different  Calibrated for individual base and medicament

48. PH 201.6648 Displacement Values  To prepare suppository of uniform and accurate weight  Must be made for the change in density of the mass due to added medicaments  So displacement value is used which is defined as  “The quantity of the drug which displaces one part of the base”

49. PH 201.6649 Displacement value of a given medicament may be determined as follows  Find out the weight of 5 suppositories  containing theobroma oil = a g  containing says 20% medicament = b g  Calculate the amount of  theobroma oil present in medicated suppositories = (80/100)*b = c g  medicament present in medicated suppositories =(20/100)*b = d g

50. PH 201.6650  Calculate the amount of theobroma oil displaced by d g of medicament = (a-c) g  Displacement value of the medicament ( amount of drug displaces 1 g of base =(d/ (a-c)

51. PH 201.6651  weight of 5 suppositories  containing theobroma oil = 5 g  containing says 40% medicament = 5.5 g  Calculate the amount of  theobroma oil present in medicated suppositories = (80/100)*5.5 = 4.4 g  medicament present in medicated suppositories = (20/100)*5.5 = 1.1 g

52. PH 201.6652  the amount of theobroma oil displaced by 1.1 g of medicament = (5 – 4.4) = 0.6 g  0.6 g theobroma oil is displaced by 1.1 g medicament  1 g theobroma oil will be displaced by =(1.1/ 0.6) = 1.8 g  Displacement value of medicament= 1.8 g

53. PH201.6753 Cold Compression Method

54. PH201.6754 Method Avoids heat and stirring Useful for thermolabile drugs and insoluble drugs Not suitable for bases where melting is required Steps involved are Cocoa butter is grated Mass is prepared by mixing powdered drug with equal quantity of grated Cocoa butter

55. PH201.6755 Then add remaining amount of grated Cocoa butter Allowance is made for unavoidable wastage during the preparation Compression of the prepared mass is done on hand or power operated compression machines

56. PH201.6756 Cold compression machine for suppositories

57. PH201.6757 Prepared mass C is placed in a cylinder A Which is forced through the narrow opening D by applying pressure to the piston B Thus forming suppositories at E Pressure is further applied, stop plate F is removed The finished suppositories are taken out

58. PH201.6758 On large scale manufacturing Hydraulically operated cold-compression machines are used Which are cooled by water jackets to prevent heat of compression from making the mass too fluid or mass and the compression cylinder of the machine may be chilled on small scale

59. PH201.6759 Package and Storage Packed in shallow partitioned card board boxes in upright position Do not allow them to come in contact with each other

60. PH201.6760 Commercial suppositories are packed separately in aluminum foil or P V Cc polyethylene strip Glycero-gelation suppositories are packed in tightly closed screw capped glass container

61. PH201.6761 Suppositories are directly moulded in to primary packing made of plastic material or aluminum foil Mould are sealed Excess is trimmed off Finally packed in cartons Stored in cold place to retain the shape

62. PH201.6762 Labeling Labeled with instructions “store in a cool place” Warning “ not to be taken orally” Or For rectal use only

63. PH201.6763 Rx Alum 300 mg Theobroma oil q.s Fiat: Suppositories mitte tales quarta Sig: Onus omni nocte utendum Displacement value of alum is 2.0

64. PH201.6764 Procedure Considering the wastage calculate for 5 suppositories instead of 4 Melt the calculated quantity of theobroma oil in a dish Pour half of melted theobroma oil on powdered alum placed on a tile

65. PH201.6765 Mix thoroughly Transfer to dish Warm if necessary Pour into the cavities of lubricated mould Keep on ice

66. PH201.6766 Fill five cavities to over flowing Allow mass to solidify Trim off excess of the mass Remove the suppositories Warm in wax paper Pack in partitioned cardboard boxes

67. PH 201-6867 Every batch of suppositories manufactured Must be tested to ensure that required standards are met Each suppository Must be visually examined for general appearance Suppository containing medicament in suspended form is sliced longitudinally to determine uniform distribution Assays must be carried out Evaluation of suppositories

68. PH 201-6868 Tests performed Uniformly of weight test Melting range test Liquefaction or softening time test Breaking test Disintegration/ dissolution test

69. PH 201-6869 Uniformity of weight test Weight 20 suppositories Average weight is calculated Each suppository is weighted individually Deviation should not be more than 5% Two should not deviate by more than 7.5%

70. PH 201-6870 Melting Range Test Also known as macromelting range test Test is performed for suppositories containing fatty base only To check physical and absorption characteristics Time taken for entire suppository to melt is measured USP tablet disintegration apparatus is used Suppository is immersed completely in constant temperature i.e., 37 o C water bath Time taken for melting is noted

71. PH 201-6871 Liquefaction Or Softening Time Test Performed on rectal suppositories A glass rod is placed on the suppository held in U –tube of the apparatus immersed in water bath Time take for the rod to pass through the suppository is recorded as softening time

72. PH 201-6872 Breaking test Or fragility test To determine tensile strength Can withstand the hazards of packing, transporting normal handling

73. PH 201-6873 Disintegration / Dissolution Test For water soluble bases Disintegration / dissolution apparatus USP are used Test media is modified accordingly

74. PH 201-6874 Factor Affecting Drug Absorption From Rectal Suppositories Release of drug and absorption depends Physiologic factors Physico-chemical characteristics of The drug The base and adjuvant

75. PH 201-6875 Physiologic Factors Number of drugs cannot be administered orally Get destroyed in the stomach Therapeutic activity is modified or reduced by liver 50-70% drugs administered through rectum are absorbed directly into blood circulation Bypassing the liver PH of rectal fluids plays an important role

76. PH 201-6876 Absorption of acidic drug increases and basic drug decreased when ph decreased Anorectal membrane also plays a role in absorption of drugs Membrane is covered with mucous which acts as mechanical barrier for free passage of drug molecules

77. PH 201-6877 Physico-Chemical characteristics of the drug Fat soluble release in slow Water soluble drug is faster Distribution depends on Nature of the drug Surfactants Physiological condition of colon and Chemical nature of the solids & liquids present in it

78. PH 201-6878 Physico -Chemical characteristics of base and adjuvants Absorption rate is faster from oily bases with low melting point Adjuvant affect dissolution of the drug