Suppository and pessries
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This document discusses suppositories and pessaries, which are semi-solid dosage forms intended for insertion into body orifices. Suppositories are meant for the rectum, vagina, or urethra and melt or dissolve at body temperature to exert localized or systemic effects. The document covers the definition, shapes and sizes, advantages, disadvantages, and ideal properties of suppository bases. It also describes common bases like cocoa butter, synthetic fats, glycero-gelatin, and macrogols (PEG), noting their properties, advantages, and disadvantages for use in suppositories.
![II] HAND ROLLING
Hand molding is useful when we are preparing a small
number of suppositories
The drug is
made into fine
powder
Incorporated
into suppository
base
By trituration or
kneading
Mass is rolled
into rod shape
by fingers
Rods are cut
into pieces
Desired shape
is given by
hand](https://image.slidesharecdn.com/suppositoryandpessries-200930123842/85/Suppository-and-pessries-42-320.jpg)
![III] COMPRESSION MOLDING -LARGE SCALE
OPERATION
Prepared mass C is placed in a cylinder A
It is forced through narrow opening D by
means of piston B into a mould.
Threads of mass pass in the mould G
and are compressed until a homogenous
fused mass is formed in E.
On removal of retaining plate F the
suppositories are ejected by further
pressure.
The mass and compression cylinder of
the machine may be chilled to prevent
heat of compression from making the
mass too fluid.
Useful for moulding suppositories
containing insoluble solids (no risk of
s e d i m e n t a t i o n ) o r t h e r m o l a b i l e
medicaments.
Unsuitable for glycero-gelatin products](https://image.slidesharecdn.com/suppositoryandpessries-200930123842/85/Suppository-and-pessries-43-320.jpg)
Suppository and pessries
- 1. SUPPOSITORIES & PESSARIES Parag Jain Assistant Professor Chhattrapati Shivaji Institute of Pharmacy Durg, Chhattisgarh Presented by
- 2. Definition • Semi-solid dosage forms intended for insertion into the body orifices where it; melt , soften dissolve and exert localized or systemic effects • A suppository is a medicated solid dosage form generally intended for use in the rectum, vagina and to a lesser extent, the urethra. • After insertion they melt or soften at body temperature, whereas vaginal suppositories sometimes called as pessaries, are also made as compressed tablets that disintegrate in body fluids.
- 3. Shape and size of suppositories
- 4. Advantages Oral route not useful. Patient – GIT problems, Nauseous or post operative. Very young , very old, or the mentally disturbed. Drug have GI side effects. Drug - not stable at GI pH or susceptible to enzymatic attack in the GI tract Drug - first pass metabolism. Drugs with an unacceptable taste can be administered. Drug that may be abused as in suicide.
- 5. Disadvantages Mucosal irritation Traditional Issues- feeling of aversion Leakage Sometimes incomplete absorption. Inter and intra subject variation. Proctitis. Large scale production difficult and costly Shelf life (stringent storage conditions) . GI state affects absorption
- 6. TYPES OF SUPPOSITORIES • Cone or torpedo shaped weighing 1 – 2 gRectal • Globular, oviform, cone or wedge shaped weighing 2 – 8 g • Made from glycero-gelatin or macrogol base Vaginal (pessaries) • Thin pencil shaped pointed at one end • Male bougies – 4 g and 100-150 mm • Female bougies – 2 g and 60 – 75 mm Urethral bougies • Thin pencil shaped with pointed ends • 1.2 g and 9 – 10 mm long Nasal bougies •Pencil shapedEar cones
- 8. Melt at body temp. Dissolve or disperse in body fluids Release any medicament readily Retain its shape when handled Non-toxic & non- irritant to mucous membrane Stable on storage Compatible with all medicaments Stable above its melting point Easily mouldable Should not adhere to the mould Properties of an ideal suppository base
- 9. TYPES OF SUPPOSITORIESBASES Suppository bases Fatty bases Cocoa Butter Synthetic fats Proprietary synthetic bases Water soluble or water miscible bases Glycero- gelatin Macrogols
- 10. Fatty bases
- 11. Properties It is the most widely used suppository base. And it is used in the prescriptions when no base is specified. It is naturally occuring triglyceride with oleopalmitostearin and oleodistearin glyceride chain and contains 40% of the unsaturated fatty acid. It is yellowish white, solid, brittle fat, which smells and tastes like chocolate. Its melting point lies between 30-35oC (86-95oF) its iodine value is between 34 - 38 and its acid value is no higher than 4. It satisfies the requirements for an ideal base – non-reactive, and melts at body temp.
- 12. Disadvantages Polymorphism Adherence to mould Low softening point Melting point reduction Deterioration during storage Poor water absorbing capacity Leakage from the body
- 13. POLYMORPHISM Polymorphism in cocoa butter is observed due to high proportion of unsaturated triglycerides. The formation of various forms of cocoa butter depends on the degree of heating, on the cooling process and on the conditions during this process. Each form of cocoa butter has different melting point and drug release rates.
- 14. Cocoa butter exits in four crystalline state α form • melts at 24oC • Obtained by suddenly cooling melted cocoa butter to 0oC. ß form • Crystallizes out of the liquefied cocoa butter with stirring at 18 to 23oC. • Its melting point lies between 28 and 31oC. ß` form • changes slowly into the stable ß form. • Melts between 34 and 35oC. • Change is accompanied by volume contraction. γ form • melts at 18oC • Obtained by pouring a cool cocoa butter, before it solidifies, into a container which is cooled at deep freeze temp.
- 15. Cocoa butter does not contract sufficiently on cooling to loosen the suppositories in the mould. Sticking may be overcome by adequate lubrication. Softening point too low for hot climates To raise the softening point, white bees wax may be added to theobroma oil suppositories intended for use in tropical and subtropical countries. 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. Adherence to the mould
- 16. Rancidity on storage: Due to the oxidation of unsaturated glycerides. Poor water- absorbing ability: Improved by the addition of emulsifying agents. Leakage from the body: Sometimes the melted base escapes from the rectum or vagina, so, it is rarely used as a pessary base. Expensive Relatively high cost
- 17. SYNTHETIC FATS To overcome the disadvantages of theobroma oil synthetic substitutes were searched. Obtained from hydrogenation and heat treatment to vegetable oils such as palm kernel and arachis. Hydrogenation saturates unsaturated glycerides and heat treatment splits some of the triglycerides into fatty acid and partial esters (mono and di glycerides). Most synthetic fat bases are made by first hydrolysing the vegetable oil, then hydrogenating the resulting fatty acids and finally esterifying the acids by heating with glycerol.
- 18. Their solidifying points are unaffected by over heating. They have good resistance to oxidation because their unsaturated fatty acids have been reduced. The difference between melting and setting points is small; generally only 1.5 to 2oC and seldom over 3oC. Hence, they set quickly, the risk of sedimentation is low and they are easier to administer. The melting point depression caused by fat soluble drugs can be counteracted by choosing a high melting point grade, while the hardness and brittleness that sometimes results from a high content of insoluble powder can be prevented by using a low melting point grade. Advantages
- 19. High softening point grades are advantageous for tropical and sub tropical formulations. They usually contain a proportion of partial glycerides some of which e.g. glyceryl monostearate, are w/o emulsifying agents and therefore their emulsifying and water absorbing capacities are good. No mould lubricant is needed because they contract significantly on cooling. They produce suppositories that are white and almost odourless and have very attractive, clean and polished appearance. Advantages
- 20. Disadvantages They are more fluid than theobroma oil when melted and at this stage sedimentation is greater. Thickeners such as magnesium stearate, bentonite reduce this problem. The release and absorption of drugs in the body may differ for theobroma oil and synthetic bases. They should not be cooled in a refrigerator or ice because they become brittle if cooled quickly.Additives such as polysorbate 80 correct this fault.
- 21. PROPRIETARY SYNTHETICBASES Whitepsol (formerly called Imhausen) • It consists of triglycerides of saturated vegetable acids (C12 to C18) with varying proportions of partial esters. • The W45 grade is used for general dispensing. Massa Estarinum • It consists of mixture of tri, di and monoglycerides of saturated fatty acids with chain lengths of C11 to C17. Grade B is recommended for general dispensing. • This differs from the previous materials in being single general purpose base with only one modification, for cold moulding. • 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. • The B.P.C allows the use of hydrogenated vegetable oils provided the melting point of the suppositories is not above 37oC. Massuppol
- 22. WATER SOLUBLE OR WATER MISCIBLE BASES
- 23. GLYCERO-GELATIN This is a mixture of glycerol and water into a stiff jelly by adding gelatin. It is used for making jellies, suppositories and pessaries and its proportion is changed according to its intended purpose. Glycero-gelatin dissolves in body secretions and therefore is preferable to a fatty base for administering antiseptics. Since, solution is slow, drug release is more prolonged than from fatty base. At present the B.P allows a maximum disintegration time of 1 hr. for Glycerol Suppositories B.P made with gelatin of B.P standard.
- 24. Disadvantages of glycero- gelatin base They are more difficult to prepare and handle. Their solution time depends on the content and quality and gelatin and the age of the base. They are hygroscopic. So a careful storage is required. It also leads to dehydration of the rectal mucosa with consequent irritation; this is an advantage where a laxative effect is required. Gelatin is incompatible with protein precipitants such as tannic acid. They have a physiological action (used as laxative)
- 25. MACROGOLS (PEG) Properties long chain polymers of ethylene oxide with general formula HOCH2(CH2OCH2)8CH2OH Exist as liquid if their average molecular range from 200 to 600 and they exist as wax like solid it is above 1000. Their water solubility, hygroscopicity and vapour pressure with increase in average molecular weight. They do not hydrolyse or deteriorate and are physiologically inert and do not support mold growth. The PEG suppositories can be prepared by both moulding and cold compression methods.
- 26. 1.The mixtures have melting point above 42oC. Hence, cool storage is not required, they are satisfactory for use in hot climates, and administration is easy because they are not slippery to handle. 2.Because of this high melting point they do not melt in the body but gradually dissolve and disperse, freeing their medication slowly and providing longer action than fatty bases. 3.Their physical properties can be varied by suitable admixture of high and low polymers. High polymers give hard products that disintegrate and release their drug slowly. ADVANTAGES OF MACROGOLS
- 27. ADVANTAGES OF MACROGOLS4.They do not stick to the mould since they contract on cooling. 5.Because of their high molecular weight solution of high viscosity are produced when they disperse in the body. 6.They absorb water well and have excellent solvent properties. 7. Products have clean smooth appearance. ADVANTAGES OF MACROGOLS
- 28. 1.They are hygroscopic so careful storage is required. Irritancy can be reduced by incorporating about 20% of water in the mass or by instructing the patient to dip the preparation in water just before insertion. This type of base is suitable for systemically active drugs. 2.Its good solvent properties can result in retention of the drug in the liquefied base in the body with consequent reduction in therapeutic activity. 3.Products sometimes fracture on storage, particularly if they contain. High solubility of macrogols which can lead to a super saturated solution in the water and subsequent crystallisation and this the mass granular and brittle. DISADVANTAGES OFMACROGOLS
- 29. 4.Crystal growth of certain medicaments may occur particularly if they are partly in solution and partly in suspension in the base. This makes the product brittle and crystals may be irritating because they are large and takes longer time to dissolve. 5.They are incompatible with bismuth salts, tannins and phenol. They lower the activity of some antibacterial agents and dissolve certain plastics necessitating care in choosing containers. DISADVANTAGES OFMACROGOLS
- 31. 1. Moulding 2. Hand rolling 3. Compression METHODS OF PREPARATION
- 33. PREPARATION BY MOLDING • The steps in molding include (a) melting the base, (b) incorporating any required medicaments, (c) pouring the melt into molds, (d) allowing the melt to cool and congeal into suppositories, (e) removing the formed suppositories from the mold. • Cocoa butter, glycerinated gelatin, polyethylene glycol, and most other bases are suitable for preparation by molding.
- 34. Suppository Molds • Molds in common use today are made from stainless steel, aluminum, brass, or plastic. • reusable and disposable Commercially available molds available for preparation of rectal, vaginal, and urethral suppositories, can produce individual or large numbers of suppositories of various shapes and sizes.
- 35. Lubrication of the Mold • Depending on the formulation, suppository molds may require lubrication before the melt is poured to facilitate clean and easy removal of the molded suppositories. • Lubrication is seldom necessary when the base is cocoa butter or polyethylene glycol. • Lubrication is usually necessary with glycerinated gelatin. • A thin coating of mineral oil applied with the finger to the molding surfaces usually suffices.
- 36. lubrication before the melt is poured to facilitate clean and easy removal of the molded suppositories
- 37. Calibration of the Mold • Each individual mold is capable of holding a specific volume of material in each of its openings. • Different bases prepared in the same mold will have different weight Because of the difference in the densities of the materials, Similarly, any added medicinal agent alters the density of the base, and the weight of the resulting suppository differs from that of those prepared with base material alone. • The pharmacist should calibrate each suppository mold for the usual base (generally cocoa butter and a polyethylene glycol base) so as to prepare medicated suppositories each having the proper quantity of medicaments.
- 38. Determination of the Amount of Base Required • Knowing the amount of drug substances provided in each suppository subtracted from the total volume of the mold will give the volume of base required. • if considerable quantities of other substances are to be used, The total volume of these materials is subtracted from the volume of the mold, and the appropriate amount of base is added. • Because the bases are solid at room temperature, the volume of base may be converted to weight from the density of the material.
- 39. Preparing and Pouring the Melt - Using the least possible heat over a water bath, the weighed suppository base material is melted on porcelain casserole . - Medicinal substances are incorporated into a portion of the melted base by mixing on a glass or porcelain tile with a spatula. - After incorporation, this material is stirred into the remaining base, which has been allowed to cool almost to its congealing point. - Any volatile materials or heat-labile substances should be incorporated at this point with thorough stirring.
- 40. Preparing and Pouring the Melt - The melt is poured carefully and continuously into each cavity of the mold, which has been previously equilibrated to room temperature. - If any undissolved or suspended materials in the mixture are denser than the base, so that they have a tendency to settle, constant stirring, even during pouring, is required, - The mold is usually placed in the refrigerator , after harding , the mold is removed from the refrigerator and allowed to come to room temperature. Then the sections of the mold are separated, and the suppositories are dislodged, with pressure being exerted principally on their ends and only if needed on the tips. - Generally, little or no pressure is required, and the suppositories simply fall out of the mold when it is opened.
- 42. II] HAND ROLLING Hand molding is useful when we are preparing a small number of suppositories The drug is made into fine powder Incorporated into suppository base By trituration or kneading Mass is rolled into rod shape by fingers Rods are cut into pieces Desired shape is given by hand
- 43. III] COMPRESSION MOLDING -LARGE SCALE OPERATION Prepared mass C is placed in a cylinder A It is forced through narrow opening D by means of piston B into a mould. Threads of mass pass in the mould G and are compressed until a homogenous fused mass is formed in E. On removal of retaining plate F the suppositories are ejected by further pressure. The mass and compression cylinder of the machine may be chilled to prevent heat of compression from making the mass too fluid. Useful for moulding suppositories containing insoluble solids (no risk of s e d i m e n t a t i o n ) o r t h e r m o l a b i l e medicaments. Unsuitable for glycero-gelatin products
- 44. 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 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
- 45. PACKAGING AND LABELLING FOR SUPPOSITORIES Rigid paperboard boxes Flat box with a lid Labelling : 1. Store in a cool place 2. For rectal use only or not to be taken orally 3. Moisten before use (for glycero-gelatin and macrogol bases)
- 46. PACKAGING AND LABELLING FOR PESSARIES Glass bottles Plastic bottles Labelling : 1. Moisten the pessaries with water before insertion to reduce stinging caused by osmotic withdrawl of water to reduce the tissues during solution in vagina. 2. For vaginal use only or not to be taken orally. 3. Store in a cool place.
- 47. Website: www.probecell.com Email: probecellinfo@gmail.com Ph: 7415211131 Office: Smriti Nagar, Bhilai, Chhattisgarh - 490020 https://youtube.com/c/ParagJainthunderpassionate https://www.facebook.com/thesisresearchwriting Research article Review article Thesis Synopsis PhD Title Research guidance