Pharmaceutics Lecture 6: Suppositories PDF

Pharmaceutics Lecture 6: Suppositories Part 2 2nd stage  Suppository bases A suppository base should remain solid at room temperature but soften, melt, or dissolve readily at body temperature so that the drug is fully available s...

Pharmaceutics Lecture 6: Suppositories Part 2 2nd stage  Suppository bases A suppository base should remain solid at room temperature but soften, melt, or dissolve readily at body temperature so that the drug is fully available soon after insertion. Certain bases are more efficient in drug release than others. Classification of Bases: A. Fatty or oleaginous bases. B. Water-soluble or water-miscible bases. C. Miscellaneous bases, generally combinations of lipophilic and hydrophilic substances. A- Fatty bases or oleaginous bases, Cocoa butter (theobroma oil): melts quickly at body temperature, but is immiscible with body fluids as for fat-soluble drugs tend to remain in the oil and have little tendency to enter the aqueous physiologic fluids. For water- soluble drugs in cocoa butter, the reverse is usually true and goodrelease results. Also, when irritation or inflammation is to be relieved, as in the treatment of anorectal disorders, cocoa butter appears to be the superior base because of its emollient or soothing, spreading action. B- Water soluble or water miscible bases (glycerinated gelatin or polyethylene glycol): Fat-soluble drugs seem to be released more readily from these bases, but, both of which dissolve slowly in body fluids. C-Miscellaneous bases: generally combinations of lipophilic and hydrophilic substances.  Effect of drug ionization and suppository base on release ◦ Un-ionized drug (HB) ◦ Ionized drug (B-) ◦ Although un-ionized drugs more For systemic drug action using a cocoa readily partition out of water- butter base, it is preferable to incorporate miscible bases such as glycerinated the ionized (salt) form rather than the un- gelatin and polyethylene glycol, the ionized (base) form of a drug to maximize bases themselves tend to dissolve bioavailability slowly and thus retard release of the drug  Fatty or Oleaginous Bases types: 1. Cocoa butter 2. Hydrogenated fatty acids of vegetable oils ,i.e. such as palm kernel oil and cottonseed oil and a mixture of oleic and stearic acids are recommended as a substitute of Cocoa Butter. 3. Fat-based compounds ,esters of glycerin with the higher molecular-weight fatty acids ,such as glyceryl monostearate and glyceryl monopalmitate. The bases in many commercial products employ varied combinations of these types of materials to achieve the desired hardness under conditions of shipment and storage and the desired quality of submitting to the temperature of the body to release their medicaments.  Cocoa Butter Fat obtained from the roasted seed of Theobroma cacao. At room temperature, it is a yellowish-white solid having a faint, agreeable chocolate-like odor (naturally occurring comp.) Chemically, the main constituent of cocoa butter is the triglyceride derived from palmitic acid, stearic acid, and oleic acid. Cocoa butter melts at 30°C to 36°C, it is an ideal suppository base, melting just below body temperature and yet maintaining its solidity at usual room temperature. However, because of its triglyceride content, cocoa butter exhibits marked polymorphism, or existence in several crystalline forms. Cocoa Butter polymorphism When cocoa butter is hastily or carelessly melted at a temperature greatly exceeding the minimum required temperature ( about 35°C) and is then quickly chilled, the result is a metastable crystalline form (alpha crystals) with a melting point much lower than that of the original cocoa butter. In fact, the melting point may be so low that the cocoa butter will not solidify at room temperature. Cocoa butter must be slowly and evenly melted, preferably over a bath of warm water, to avoid formation of the unstable crystalline form and ensure retention in the liquid of the more stable beta form crystals having the greater stability and a higher melting point.  lowering Melting point Substances such as phenol and chloral hydrate have atendency to lower the melting point of cocoa butter. If the melting point is low enough that it is not feasible to prepare a solid suppository using cocoa butter alone as the base, solidifying agents like cetyl esters wax (about 20%) or beeswax (about 4%) may be melted with the cocoa butter to compensate for the softening effect of the added substance. However, the addition of hardening agents must not be so excessive as to prevent the base from melting in the body, nor must the waxy material interfere with the therapeutic agent in any way so as to alter the efficacy of the product.  Water-Soluble and Water-Miscible Bases Glycero-gelatin (Glycerinated gelatin) base and PEGs : Glycerinated gelatin suppositories may be prepared by dissolving gelatin (20%) in glycerin (70%) and adding water or a solution or suspension of the medication (10%). The stiffness of the mass depends upon the proportion of gelatin used. A glycerinated gelatin base is most frequently used in preparation of vaginal suppositories, with which prolonged local action of the medicinal agent is usually desired. The glycerinated gelatin base is slower to soften and mix with the physiologic fluids than cocoa butter and therefore provides a slower release. Glycero-gelatin base suppositories are less commonly used than the fatty base suppositories because of its following Disadvantages: 1. Glycerol exerts laxative action. 2. They are hygroscopic in nature and hence must be carefully stored due to nature of glycerin. 3. suppository may have a dehydrating effect and irritate the tissues upon insertion. Water in the formula for the suppositories minimizes this action; however, if necessary, the suppositories may be moistened with water prior to insertion to reduce the initial tendency of the base to draw water from the mucous membranes and irritate the tissues.  Polyethylene glycols (PEGs) (Macrogols) ❑ Polymers of ethylene oxide and water prepared to various chain lengths, molecular weights (No.), and physical states ❑ PEGs Hardness increases with an increase in the molecular weight. ❑ Various combinations of these polyethylene glycols may be combined by fusion, using two or more of the various types to achieve a suppository base of the desired consistency and characteristics. Polyethylene glycol suppositories do not melt at body temperature but rather dissolve slowly in the body’s fluids. Therefore, the base not need to be formulated to melt at body temperature. Thus, suppositories from mixtures prepared having melting points considerably higher than body temperature to permits a slower release of the medication from the base , and permits convenient storage of these suppositories without need for refrigeration. Further, their solid nature permits slow insertion without fear that they will melt in the fingertips (as cocoa butter suppositories sometimes do). Polyethylene glycol suppositories that do not contain at least 20% water should be dipped in water just before use to avoid irritation of the mucous membranes after insertion.  Miscellaneous Bases In the miscellaneous group of bases are mixtures of oleaginous and water- soluble or water-miscible materials. ✓These materials may bechemical or physical mixtures. ✓Some are preformed emulsions, generally of the water-in-oil type, or they may be capable of dispersing in aqueous fluids. Example is Polyoxyl 40 stearate. The substance is a white to light tan waxy solid that is water soluble. Its melting point is generally 39°C to 45°C.  Preparation of Suppositories Calibration of the Mold Each individual mold is capable of holding a specific volume of material in each of its openings. Because of the difference in the densities of the materials, different bases prepared in the same mold will have different weight. The base is cocoa butter, the weight of the suppositories will differ from the weight of that prepared in the same mold with a base of PEGs.  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.