Pharmaceutical suppositories


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Pharmaceutical suppositories

  1. 1. SUPPOSITORIESRakesh Kumar Sharma Rakesh Kumar Sharma 1
  2. 2. OBJECTIVES:AFTER THE END OF THIS TOPIC ,STUDENTS WILL BE ABLE TO :Define suppositories and pessaries.Differentiate between suppositories and pessaries.Classify suppositoriesAdvantages & disadvantages of suppositories.Discuss different suppository bases used.Discuss the different method of preparation Rakesh Kumar Sharma 2
  3. 3. Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert localized or systemic effects. Rakesh Kumar Sharma 3
  4. 4. Dosage form characteristics:a. Rectal suppositories for adults weigh 2 gm and are torpedo shape.Childrens suppositories weigh about 1 gm.b. Vaginal suppositories or Pessaries weigh about 3-5gm and are molded in globular or oviform shape or compressed on a tablet press into conical shapes. Rakesh Kumar Sharma 4
  5. 5. c. Urethral suppositories called bougies are pencil shape. Those intended for males weigh 4 gm each and are 100-150 mm long.those for females are 2 gm each and 60-75 mm in length.d. Nasal suppositories: called nasal bougies or buginaria meant for introduction in to nasal cavity.They are prepared with glycerogelatin base.They weigh about 1 gm and length 9-10 cm. Rakesh Kumar Sharma 5
  6. 6. e. Ear cones:Aurinaria and meant for introduction into ear.Rarely usedTheobroma oil is used as base.Prepared in urethral bougies mould and cut according to size. Rakesh Kumar Sharma 6
  7. 7. ADVANTAGES:_ Can exert local effect on rectal mucosa._ Used to promote evacuation of bowel._ Avoid any gastrointestinal irritation._ Can be used in unconscious patients (e.g. during fitting)._ Can be used for systemic absorption of drugs and avoid first-pass metabolism.− Babies or old people who cannot swallow oral medication.− Post operative people who cannot be administered oral medication.− People suffering from severe nausea or vomiting. Rakesh Kumar Sharma 7
  8. 8. DISADVANTAGES OF SUPPOSITORIES:− The problem of patient acceptability.− Suppositories are not suitable for patients suffering from diarrhea.− In some cases the total amount of the drug must be given will be either too irritating or in greater amount than reasonably can be placed into suppository.− Incomplete absorption may be obtained because suppository usually promotes evacuation of the bowel. Rakesh Kumar Sharma 8
  9. 9. Rakesh Kumar Sharma 9
  10. 10. SUPPOSITORIES:British Pharmacopoeia (BP) definition: “Suppositories are solid, single-dose preparations. The shape, volume and consistency of suppositories are suitable for rectal administration.” Rakesh Kumar Sharma 10
  11. 11. Pessaries are a type of suppository intended for vaginal use.The larger size moulds are usually used in the preparation of pessaries such as 4 g and 8 g moulds.Pessaries are used almost exclusively for local medication, the exception being prostaglandin pessaries that do exert a systemic effect. Rakesh Kumar Sharma 11
  12. 12. IDEAL SUPPOSITORY BASE:1. Melts at body temperature or dissolves in body fluids.2. Non-toxic and non-irritant.3. Compatible with any medicament.4. Releases any medicament readily.5. Easily moulded and removed from the mould.6. Stable to heating above the melting point.7. Easy to handle.8. Stable on storage. Rakesh Kumar Sharma 12
  13. 13. I FATTY BASES: designed to melt at body temperature.1- Theobroma oil (Cocoa butter)It is a yellowish-white solid with an odour of chocolate and is a mixture of glyceryl esters of different unsaturated fatty acids. Rakesh Kumar Sharma 13
  14. 14. Advantages:a- A melting range of 30 - 36°C (solid at room temperature but melts in the body).b- Readily melted on warming, rapid setting on cooling.c- Miscible with many ingredients.d- Non-irritating. Rakesh Kumar Sharma 14
  15. 15. Disadvantages:a- Polymorphism:- When melted and cooled it solidifies in different crystalline forms, depending on the temperature of melting, rate of cooling and the size of the mass.- If melted at not more than 36°C and slowly cooled it forms stable beta crystals with normal melting point.- If over-heated then cooled it produce unstable gamma crystals which melt at about 15°C or alpha crystals melting at 20°C.Cocoa butter must be slowly melted avoid the formation of the unstable crystalline form. Rakesh Kumar Sharma 15
  16. 16. b- Adherence to the mould:c- Softening point too low for hot climates.d- Melting point reduced by soluble ingredients: Phenol and chloral hydrate have a tendency to lower the melting point of cocoa butter.- So, solidifying agents like beeswax (4%) may be incorporated to compensate for the softening effect of the added substance.e- Rancidity on storage:f- Poor water-absorbing ability: Improved by the addition of emulsifying agents.g- Leakage from the body:h- Expensive Rakesh Kumar Sharma 16
  17. 17. SYNTHETIC HARD FAT:- For example: Suppocire, witepsol.Advantages:a- Their solidifying points are unaffected by overheating.b- They have good resistance to oxidation because of the lower content of unsaturated fatty acids.c- The difference between melting and setting points is small. Hence they set quickly, the risk of sedimentation of suspended ingredients is low. Rakesh Kumar Sharma 17
  18. 18. d- They are marketed in a series of grades with different melting point ranges, which can be chosen to suit particular products and climatic condition.e-They contain a proportion of w/o emulsifying agents, and therefore, their water-absorbing capacities are good.f- No mould lubricant is necessary because they contract significantly on cooling. Rakesh Kumar Sharma 18
  19. 19. Disadvantages:a- Brittle if cooled rapidly, avoid refrigeration during preparation.b- The melted fats are less viscous than theobroma oil. As a result greater risk of drug particles to sediment during preparation lack of uniform drug distribution give localized irritancy. Rakesh Kumar Sharma 19
  20. 20. II Water-soluble and water-miscible bases:1- Glycero-gelatin:The commonest is Glycerol Suppositories Base B.P., which has 14% w/w gelatin, and 70% w/w glycerol & water Q.S. to 100%. . The glycerol-gelatin base U.S.P. consisted of 20% w/w gelatin, and 70% w/w glycerol & water Q.S. to 100%. Rakesh Kumar Sharma 20
  21. 21. DISADVANTAGES:a- A physiological effect: osmosis occurs during dissolving in the mucous secretions of the rectum, producing a laxative effect.b- Can cause rectal irritation due to small amount of liquid present.c- Unpredictable solution time.d- Hygroscopic: So, they should be packaged in tight containers and also have dehydrating effects on the rectal and vaginal mucosa leading to irritation.e- Microbial contamination likely.f- Long preparation time. Rakesh Kumar Sharma 21g- Lubrication of the mould is essential.
  22. 22. 2- Macrogols (polyethylene glycols):- Polyethylene glycols are polymers of ethylene oxide and water, prepared to various chain lengths, molecular weights, and physical states.- The numerical designations refer to the average molecular weights of each of the polymers.- Rakesh Kumar Sharma 22
  23. 23. Polyethylene glycols (PEGs) having averagemolecular weights of 300, 400, and 600 are clear,colorless liquids, while those with molecularweights of 600-1000 are semisolids.-Those having average molecular weights ofgreater than 1000 are wax-like, white solids withthe hardness increasing with an increase in themolecular weight.These polyethylene glycols can be blended togetherto produce suppository bases with varying: meltingpoints, dissolution rates and physicalcharacteristics. Rakesh Kumar Sharma 23
  24. 24. Drug release depends on the base dissolving rather than melting.The melting point is often around 50°C.Higher proportions of high molecular weight polymersproduce preparations which release the drug slowly and are also brittle. Less brittle products which release the drug more readily can be prepared by mixing high polymers with medium and low polymers. Rakesh Kumar Sharma 24
  25. 25. Preparation of suppositories:Suppositories are prepared by four methods:I Hand moulding:-Hand molding is useful when we are preparing small number of suppositories:1. The drug is made into a fine powder.2. It is incorporated into the suppository base by kneading with it or by trituration in a mortar.3. The kneaded mass is rolled between fingers into rod shaped units.4. The rods are cut into pieces and then one end is pointed. Rakesh Kumar Sharma 25
  26. 26. II Compression molding:1. The cold mass of the base containing the drug is compressed into suppositories using a hand operated machine. Rakesh Kumar Sharma 26
  27. 27. **Advantages:1.It is a simple method.2. It gives suppositories that are more elegant than hand moulded suppositories.3. In this method sedimentation of solids in the base is prevented.4. Suitable for heat labile medicaments.**Disadvantages:1.Air entrapment may take place.2.This air may cause weight variation.3.The drug and/or the base may be oxidized by this air. Rakesh Kumar Sharma 27
  28. 28. III Pour moulding:- Using a supp. mould which is made of metal or plastic. Traditional metal moulds are in two halves which are clamped together with a screw.Steps:1. The base is melted and precautions are taken not to overheat it.2. The drug is incorporated in it.3. The molten liquid mass is poured into chilled(lubricated if cocoa butter or glycrogelatin is the base)molds.4. After solidification the cone shaped suppositories are Rakesh Kumar Sharma 28
  30. 30. Calibration of the Moldwhy need? Individual mold is capable of holding a specific volume of material. Because of the difference in the densities of the materials (Supp. Base and medicament), Different bases produce suppositories with different weight. Suppository mold closed Suppository mold opened Rakesh Kumar Sharma 30
  31. 31. Method of calibrationPrepare molded suppositories frombase material alone. After removalfrom the mold, the suppositories areweighed and the total weight andaverage weight of each suppository arerecorded (for the particular base used). Rakesh Kumar Sharma 31
  32. 32. Displacement value or Density factorTo prepare the suppositories of uniform and accurate weight,allowance must be made for the change of in the density(Supp.Base and Medicament) for that the displacement value of themedicament is taken into consideration. Rakesh Kumar Sharma 32
  33. 33. Displacement value or density factor is defined as“ the quantity of the drug which displaces one partof the base"Amount of Base displaced= Weight of themedicament Displacementvalue(DV) (Density factor)Example:DV of aspirin=1.3 that is 1.3gm of aspirin willdisplace 1.0 gm of cocoa butter or 1.3 gm ofaspirin will occupy the volume equal to thevolume occupied by 1.0g of cocoa butter, usingstd suppository moldDV of Boric acid= 1.5DV of Potassium Bromide = 2.2 Rakesh Kumar Sharma 33
  34. 34. Displacement value or Density factor can also becalculated = Density of the medicament Density of the baseExample: Prepare 10 suppositories, each containing200 mg of a drug with a density of 3.0. The basehas a density of 0.9, and a prepared blank weighs2.0 g. Using the determination of occupied volumemethod, preparethe requested suppositories. Rakesh Kumar Sharma 34
  35. 35. From step 1: The average weight per mold is 2.0g.From step 2: The quantity required for 10suppositories is 2 × 10 g = 20 g.From step 3: The density ratio is 3.0/0.9 = 3.3.From step 4: The amount of suppository basedisplaced by the active drug is 2.0 g/3.3 = 0.6 g.From step 5: The weight of the base required is20 − 0.6 g = 19.4 g.From step 6: The quantity of active drugrequired is 0.2 × 10 g = 2.0 g.The required weight of the base is 19.4 g, andthe weight of the active drug is 2 g. Rakesh Kumar Sharma 35
  36. 36. Note: If you are using polyethylene glycolas your base, multiply the cocoa butterreplaced by 1.25 to find the amount ofpolyethylene glycol replaced. In preparationof suppositories, it is generally assumed that ifthe quantity of active drug is less than 100 mg,then the volume occupied by the powder isinsignificant and need not be considered. This isusually based on a 2-g suppository weight.Obviously, if a suppository mold of less than 2 gis used, the powder volume may need to beconsidered. Rakesh Kumar Sharma 36
  37. 37. IV Automatic Moulding machine:All the operations in pour moulding are done by automatic machines. Using this machine, up to about 10,000 suppositories per hour can be produced. Rakesh Kumar Sharma 37
  38. 38. Rakesh Kumar Sharma 38
  39. 39. Packaging and storage:-Suppositories are usually packed in tin or aluminium, paper or plastic.-Poorly packed suppositories may give rise to staining, breakage or deformation by melting.-Both cocoa butter and glycerinated gelatin suppositories stored preferably in a refrigerator.- Polyethylene glycol suppositories stored at usual room temperature without the requirement of refrigeration. Rakesh Kumar Sharma 39