SUPPOSITORIES , VAGINAL, RECTAL, NASAL, EAR,

SUPPOSITORIES

1. SUPPOSITORIES PREPARED BY – FAYEJA S ZANKHWALA ASSISTANT PROFESSOR

2. Suppositories are single solid dosage forms intended for insertion into body orifices/cavities ( nasal, vagina, rectal, ear, nose ) where they melt, soften, or dissolve and exert localized or systemic effects. It must dissolve in the body cavity fluid to release of drug The suppository can be used for both Local & systemic action even can be use in unconscious patient. The suppositories are available in different weight, size & shapes.

3. They contain one or more active substances dispersed or dissolved in a suitable basis which may be soluble or dispersible in water or may melt at body temperature. Excipients used such as diluents, adsorbents, surface-active agents, lubricants, antimicrobial preservatives and coloring matter

4. ADVANTAGES EASILY ADMINSTERED to children, old persons, to unconscious or sometimes to mentally unstable persons who cannot swallow the drug. Convenient mode of administration for drugs which irritate the GIT, causing vomiting and destroyed in acidic pH of stomach and enzymes of GIT. FASTER ONSET OF ACTION as compared to oral administration because absorption of drug through rectal mucosa directly reaches blood 4

5. DISADVANTAGES They are not acceptable by the patients. The manufacturing process is difficult. The drugs which cause irritation to the mucous membrane cannot be administered as suppositories. Most of the suppositories should be stored at low temperature10-20°c in a refrigerator , other wise the base gets liquified. 5

6. Moulds for suppositories

7. Classification Of Suppositories Rectal suppositories Vaginal suppositories ( PESSARIES ) Urethral suppositories ( BOUGIES ) Nasal suppositories Ear suppositories

8. VAGINAL SUPPOSITORY They are also called as PESSARIES. SHAPE : globular, oviform or cone-shaped. Used occasionally. Weight 4-8 gm Intended for local effects like contraceptives, antiseptics in feminine hygiene 8

9. URETHRAL SUPPOSITORY Also called as BOUGIES . SHAPE – slender, pencil-shaped. Weight 2-4gm Intended for anti-bacterial or as a local anesthetic preparative for urethral examination. Occasionally used. 9

10. RECTAL SUPPOSITORY Intended for local action to relieve constipation, irritation, itching and inflammatory associated to hemorrhoids 1-2 g wt Cone or torpedo shape 10

11. Introduced into nasal cavity also known as nasal bougies . Similar to urethral suppository. Thin , cylindrical shape Always Prepared with glycero – gelatin base. 9-10cm long and wt 1 g. NASAL SUPPOSITORY

12. Used for internal ear and also called aurinaria . Long , thin, and cylindrical shape. Weight about 1 gm Rarely used. Usually prepared with theobroma oil. EAR CONES

13. Classification Of Suppositories Via Position Of Action LOCAL EFFECT : In case of pain, itching and hemorrhoid. Locally active drugs include astringents, antiseptics, local anesthetics, vasoconstrictors, anti-inflammatory, soothing and protective agents and some laxatives. SYSTEMIC EFFECT : Anti-asthmatics, anti rheumatics, anti-pyretic and analgesics 13

14. Types of Suppositories

15. Formulation of suppositories Bases Anti- oxidants Emulsifying agents Hardening agents Preservatives Thickening agents Plasticizers 15

16. IDEAL PROPERTIES OF SUPPOSITORY BASES It should melt at body temperature or dissolve or disperse in body fluids. It should be good appearance It should release any medicament easily. It should keep its shape when being handled. It should be non-toxic and non-irritant to the mucous membrane. It should be stable on storage and also stable if heated above its M.P. 16

17. IDEAL PROPERTIES OF SUPPOSITORY BASES It should be easily molded and should not adhere to the mold. It should possess good wetting and emulsifying properties. It should be able to incorporate a high percentage of water. It should be chemically and physically stable 17

18. IDEAL PROPERTIES OF SUPPOSITORY BASES If the base is fatty, it has the following additional requirements : Acid value is below 0.2. Saponification value ranges from 200 to 245. Iodine value is less than 7. The interval between melting point and solidification point is small.

19. SUPPOSITORY BASES Classification of suppository bases 1. Fatty bases – they melt at body temperature. 2. Water-soluble or water miscible base – they dissolve or disperse in rectal secretions. 3. Emulsifying bases – they emulsifies small amount of aqueous solution of drug.

20. 1 FATTY BASES Example: Theobroma oil (Cocoa butter), Synthetic fats. Theobroma oil (Cocoa butter) It is a yellowish-white solid having chocolate flavor. It is a mixture of glyceryl esters of stearic , palmitic , oleic and other fatty acids Advantages: melting point 30-36 solid at normal room temperatures but melts in the body Ready liquefaction on warming and rapid setting on cooling. Miscibility with many ingredients

21. Disadvantages Relatively costly Immiscible with body fluid Leakage from body cavities Poor water absorbing capacity Adherence to mould

22. 2. WATER SOLUBLE AND WATER MISCIBLE BASES 1- Glycero -Gelatin base This is a mixture of glycerol and water made into a stiff jelly by adding gelatin. The base being hydrophilic in nature, slowly dissolves in the aqueous secretions and provide a slow continuous release of medicament. Glycerogelatin base is well suited for suppositories containing belladonna extract, boric acid, chloral hydrate, bromides, iodides, iodoform , opium, etc.

23. Depending upon the compatibility of the drugs used a suitable type of gelatin is selected for the purpose. Two types of gelatin used as suppository base: ( i ) Type-A or Pharmagel -A which is made by acid hydrolysis Acidic drugs having isoelectric point between 7 to 9 (ii) Type-B or Pharmagel -B which is prepared by alkaline hydrolysis Alkaline drugs having isoelectric point between 4.7 to 5

24. Disadvantages: Glycerol has laxative action. Their solution time depends on the content and quality of the gelatin used. Gelatin is incompatible with drugs those precipitate with the protein e.g. tannic acid, ferric chloride, gallic acid, etc. They are more difficult to prepare and handle.

25. 3. EMULSIFYING BASES These are synthetic bases and a number of proprietary bases of very good quality are available, few of which are described below: Witepso They consist of triglycerides of saturated vegetable acids (chain length C12 to C18) with varying proportions of partial esters. Massa Esterium This is another range of bases, consisting of a mixture of di -, tri- and mono- glycerides of saturated fatty acids with chain lengths of C11 to C17. Massuppol It consists of glyceryl esters mainly of lauric acid, to which a small amount of glyceryl monostearate has been added to improve its water absorbing capacity.

26. Other excipients Anti-oxidants They protect the drug and the base from getting degraded due to oxidation. Examples : Ethyl or propyl gallate Ascorbic acid and its esters Hydroquinone Tocopherols Emulsifying agents They increase the water-absorbing capacity of fatty bases. This makes it possible to include aqueous solutions in the formulation. Examples : polysorbates ( tween 61) Wool alcohol ,wool fat 26

27. Hardening agents: These are included in those formulations where the melting point of the base is decreased by the drug. These agents bring the melting point to normal. Examples : macrogols with high molecular weight . Preservatives : They should be included in suppositories which contain water soluble bases to prevent microbial growth. Examples :methyl paraben , propyl paraben

28. Thickening Agents : They increase the viscosity of molten base and prevent sedimentation of suspended insoluble solids. Examples: Aluminium monostearate , collodial silica, magnesium stearate . Plasticizer They impart plasticity to the fatty base and makes it less brittle. Examples : Castor oil Glycerine or propylene glycol Glycol Tween 80 Tween 85

29. PREPARATION METHODS Suppositories are prepared by four methods:- HAND MOLDING METHOD COMPRESSION MOLDING METHOD POUR MOLDING METHOD AUTOMATIC MOLDING METHOD .

30. HAND MOLD SUPPOSITORIES

31. Advantages:- Suitable for thermo labile ingredients. Economical for the manufacture of small number of suppositories. Disadvantages:- No uniformity in shape & size of suppository. HAND MOLD SUPPOSITORIES

32. COMPRESSION MOLD SUPPOSITORIES [ COLD COMPRESSION]

33. Advantages:- Suitable for thermo labile drugs. No possibility of settling of the insoluble solids in base. Disadvantages:- Rate of production is low so not suitable for large scale. Air get entrapped in the mass which leads to oxidation of ingredients. COMPRESSION MOLD SUPPOSITORIES [ COLD COMPRESSION]

34. FUSION OR MELT OR POUR MOLD SUPPOSITORIES

35. Incorporation of drug: Solid:-drug and additive powder mixed on warm tile Semisolid:-triturate the ingredients on warm tile with water. this decrease the viscosity and give homogenous liquid. Liquid:- Volatile liquid:-they can be added to the molten base directly. Nonvolatile liquid:- same as semisolid. FUSION OR MELT OR POUR MOLD SUPPOSITORIES

36. All filling , ejection and mold cleaning operations are fully automatic Output – 3500 to 6000 suppositories per hour Suppository mold is lubricated with brushing or spraying and then filled to a slight excess Excess material is removed after the mass gets solidified and collected for re – use AUTOMATIC MOLD MACHINE

37. PACK AND LABEL Packing of suppositories:- It can be foiled in aluminum ,plastic, paper, tin strip. Modern packing machine: nearly 8000 suppositories can be wrapped per hour. In packing molding : In this ,the suppository mass is directly move into the series of molds which are made up of plastic. After cooling , excess mass is trimmed of . By this technique 12,000 to 15,000 suppositories can be produce per hour. Disposable molds:- They are suitable for tropical climate. They are made up of plastic or aluminum . Labeling:- “store in a cool place.” “Not to be taken orally.”

38. EVALUATION OF SUPPOSITORIES Appearance Uniformity of weight Disintegration Test for uniformity of drug content Breaking test Softening time Test of melting rang Test for Dissolution rate

39. APPEARANCE Odor Color Surface condition Shape They may contain several layers Instabilities are identified based on changes in surface texture , color,odor

40. WEIGHT VARIATION Weigh individually 20 suppositories Weigh 20 at a time Calculate average weight Limit: not more than 2 suppository differ from the average weight by more than 5% and no suppository differs from average weight by more than 10%

41. HARDNESS or BREAKING TEST PLACE THE SUPPOSITORY IN THE INSTRUMENT ADD 600g, leave it for 1 min If not broken add 200 gm every 1minute untill suppository is broken