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Compounding Suppository Dr. Muslim Suardi, MSi., Apt. Faculty of Pharmacy University of Andalas Suppositories Are medicated, solid bodies of various sizes & shapes suitable for introduction into body cavities. The medicament is incorporated into a base such as cocoa butter which melts at body temperature, or into one such as glycerinated gelatin or PEG which slowly dissolves in the mucous secretions. Action Local action Systemic effect To exert a mechanical effect to facilitate emptying the lower bowel Ideal Suppository Base Nontoxic Nonirritating Inert, compatible with medicaments Easily formed by compression or molding. Dissolve or disintegrate in the presence of mucous secretions or melt at body temperature to allow for the release of the medication. Role of Suppository Base As with the ointment bases, suppository base composition plays an important role in both the rate & extent of release of medications Utilize Suppositories Medicated solid formulations that are inserted into body cavities. Made in a variety of shapes & sizes because they are used in many different ROA (body cavities). Rectal Drugs administered via the rectum are given for a local effect or to achieve a systemic effect. Local effects may include the soothing of inflamed hemorrhoidal tissues, promoting laxation, & enemas. Rectal Administration To achieve systemic activity is preferred when the drug is destroyed in the GIT, if oral administration is not possible because of vomiting, or the patient is unconscious or incapable of swallowing oral formulations. Has been used to treat a variety conditions such as asthma, nausea, motion sickness, anxiety, & bacterial infections. Common Rectal Formulations Suppositories Solutions Ointments Suppositories Solid dosage forms that dissolve or melt when inserted into the rectum. Manufactured in a variety of shapes. Rectal suppositories for adults are tapered at one end & usually weigh 2g. Infant rectal suppositories usually weight ±1g or ± 1/2 of adult supp Major Disadvantages Rectal absorption of most drugs is frequently erratic & unpredictable. Some suppositories "leak" or are expelled after insertion. They are not preferred by patients; they are inconvenient. Vaginal Administration Advantages Generally there is less drug degradation via this ROA compared to oral administration The dose can be retrieved if necessary There is the potential of long term drug absorption with various IUDs Vaginal Administration Lead to variable absorption since the vagina is a physiologically & anatomically dynamic organ that causes pH & membrane permeability to change over time. There is also a tendency of some dosage forms to be expelled after insertion into the vagina. Vaginal Formulations Include: solutions, powders for solutions, ointments, creams, aerosol foams, suppositories, & tablets. Vaginal suppositories are employed as contraceptives, feminine hygiene antiseptics, bacterial antibiotics, or to restore the vaginal mucosa. Are inserted high in the vaginal tract with the aid of a special applicator Shape Usually globular, oviform, or coneshaped & weigh between 3-5g Patients should be instructed to quickly dip the suppository in water before insertion. Because they are generally used at bedtime & can be messy if the formulation is an oleaginous base, patients should wear a sanitary napkin to protect nightwear & bed linens. Urethral Suppositories Not specifically described in the USP 24 either by weight or dimension. Traditionally, they are cylindrical in shape (3-6 mm in diameter) & vary in length according to gender. Female Urethral Suppositories Can be 25-70 mm in length while male urethral suppositories can be about 50-125mm in length. The one commercially available urethral suppository is actually marketed as a "pellet," & is 1.4 mm in diameter & 3 or 6 mm in length depending on strength. They are unusual & may not be Inserting Rectal Suppositories If possible, go to the toilet & empty bowels. Wash hands carefully with soap & warm water. Remove any foil or plastic wrapping Lubricate the tapered end of the suppository with a small amount of KY® Jelly. If the jelly is not available, moisten it with a small amount of Inserting Rectal Suppositories Separate buttocks to expose the rectal area. Gently but firmly push the suppository into the rectum until it passes the sphincter (±1/2-1 inch in infants, & 1 inch in adults. Inserting Rectal Suppositories Close your legs & sit (or lay) still for ±15min. Avoid emptying bowels for at least 1h (unless the suppository is a laxative). Avoid excessive movement or exercise for at least 1h Wash hands again with soap & warm water immediately after inserting the suppository. Inserting Vaginal Suppositories Wash hands with soap & warm water. Remove any foil or plastic wrapping Place suppository in applicator. Hold the applicator by the opposite end from where the suppository is. Either lay on your back with your knees bent, or stand with your feet spread a few inches apart & your knees bent. Inserting Vaginal Suppositories Gently insert the applicator into the vagina as far as it will go comfortably. Once you are ready, push the inside of the applicator in & place the suppository as far back in the vagina as possible. Remove the applicator for the vagina. Wash your hands again with soap & warm water Suppository Bases Suppository bases may be conveniently classified as according to their composition & physical properties: Oleaginous (fatty) bases Water soluble or miscible bases Oleaginous Bases Include Theobroma Oil & synthetic triglyceride mixtures. Theobroma Oil or cocoa butter is used as a suppository base because, in large measure, it fulfills the requirements of an ideal base. Oleaginous Bases At ordinary room temp of 15-25°C (59-77°F), it is a hard, amorphous solid, but at 30-35°C (86-95°F), i.e., at body temperature, it melts to a bland, nonirritating oil. Thus in warm climates, theobroma oil suppositories should be refrigerated. Preparing Suppositories with Cocoa Butter 2 factors of particular attention: First, this base must not be heated above 35°C (95°F) because cocoa butter is a polymorphic compound & if overheated will convert to a metastable structure that melts in the 25-30°C (77-86°F) range. Finished suppositories would melt at room temperature & not be usable. Preparing Suppositories with Cocoa Butter The second factor is the change in mp caused by adding certain drugs to cocoa butter supp. E.g: chloral hydrate & phenol tend to lower the mp. It may be necessary to add spermaceti /beeswax to raise the mp of finished supp back to the desired range. Synthetic Triglycerides The newer base. Consist of hydrogenated vegetable oils. Advantage over cocoa butter: not exhibit polymorphism. More expensive Some of the bases are single entity formulations. Some may denote a series of bases. Bases are varied to give a range of mp Synthetic Triglycerides E.g: Fattibase® is a single entity base that consists of triglycerides from palm, palm kernel, & coconut oils. Wecobee® is a series of bases. Wecobee FS, M, R, & S are all made from triglycerides of coconut oil. But FS has a mp range of 39.4 to 40.5°C, M has a range of 33.3 to 36.0°C, R has a range of 33.9 to Water Soluble/Water Miscible Bases Ccontaining glycerinated gelatin or the PEG polymers. Glycerinated Gelatin A useful supp base, particularly for vaginal supp. Suitable for use with a wide range of medicaments including alkaloids, boric acid, & ZnO. Glycerinated gelatin supp are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in mucous secretions to provide Supp Made with Glycerinated Gelatin Must be kept in well-closed containers in a cool place since they will absorb & dissolve in atmospheric moisture. Intended for extended shelf-life should have a preservative added, such as nipagin/nipasol, or a suitable combination of the two. To facilitate administration, glycerinated gelatin supp should be PEG Polymers Have received much attention as supp bases in recent years because they possess many desirable properties. Chemically stable, nonirritating, miscible with water & mucous secretions, & can be formulated, either by molding or compression, in a wide range of hardness & mp. Like glycerinated gelatin, they do not melt PEG Polymers May be used singly as supp bases but, more commonly, formulas call for compounds of 2 or more MW mixed in various proportions as needed to yield a finished product of satisfactory hardness & dissolution time. PEG Polymers Since the water miscible supp dissolve in body fluids & need not be formulated to melt at body temperature, they can be formulated with much higher mp & thus may be safely stored at room temperature. Methods of Preparation Suppositories can be extemporaneously prepared by: 1. Hand Rolling 2. Compression Molding 3. Fusion Molding 1. Hand Rolling The oldest & simplest method of supp preparation & may be used when only a few suppositories are to be prepared in a cocoa butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-like mass is prepared by triturating grated cocoa butter & active ingredients in a mortar. 1. Hand Rolling The mass is formed into a ball in the palm of the hands, then rolled into a uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape. 1. Hand Rolling Effective hand rolling requires considerable practice & skill. The suppository "pipe" or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded & softened. 2. Compression Molding is a method of preparing suppositories from a mixed mass of grated suppository base and medicaments which is forced into a special compression mold. 2. Compression Molding The method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies & weighing the finished supp. When API are added, it is necessary to omit a portion of the supp base, based on the density factors of the API. 3. Fusion Molding Involves first melting the supp base, & then dispersing or dissolving the drug in the melted base. The mixture is removed from the heat & poured into a supp mold. When the mixture has congealed, the supp are removed from the mold. The fusion method can be used with all types of supp & must be used with Suppository Volume Supp are generally made from solid ingredients & drugs which are measured by weight. When they are mixed, melted, & poured into supp mold cavities, they occupy a Vol-the vol of the mold cavity Since the components are measured by weight but compounded by volume, density calculations & mold When a drug is placed in a suppository base, it will displace an amount of base as a function of its density. If the drug has the same density as the base, it will displace an equivalent weight of the base. If the density of the drug is greater than that of the base, it will displace a proportionally smaller weight of the base. Density factors for common drugs in cocoa butter are available in standard reference texts. The density factor is used to determine how much of a base will be displaced by a drug. The relationship is: Eg. ASA has a density factor in cocoa butter of 1.3. If a supp is to contain 0.3g of ASA, it will replace 0.3g÷1.3 or 0.23g of cocoa butter. If the blank supp (supp without the drug) weighed 2g, then 2g-0.23g or 1.77 g of cocoa butter will be needed for each supp, & the supp will weigh 1.77g+0.3g=2.07g So if a pharmacist was making 12 aspirin supp using cocoa butter as the base, he would weigh 1.77g×12=21.24g of cocoa butter & 0.3g×12=3.6g of ASA Some Density Factors of Drugs in Cocoa Butter Medicaments Density Factor Aspirin 1.3 Barbital 1.2 Bismuth salicylate 4.5 Chloral hydrate 1.3 Cocaine hydrochloride 1.3 Codeine phosphate 1.1 Diphenhydramine hydrochloride 1.3 Morphine hydrochloride 1.6 Hand Rolling The oldest & simplest method of supp preparation & may be used when only a few supp are to be prepared in a cocoa butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-like mass is prepared by triturating grated cocoa butter & API in a mortar. Hand Rolling The mass is formed into a ball in the palm of the hands, then rolled into a uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape Hand Rolling Effective hand rolling requires considerable practice & skill. The supp "pipe" or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded & softened. 2. Compression Molding Method of preparing supp from a mixed mass of grated supp base & medicaments which is forced into a special compression mold. The method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies & weighing the finished supp. When active ingredients are added, it is necessary to omit a portion of the supp base, based on the density factors of the active ingredients 3. Fusion Molding Involves first melting the supp base, & then dispersing/dissolving the drug in the melted base. The mixture is removed from the heat & poured into a supp mold. When the mixture has congealed, the supp are removed from the mold. Fusion method can be used with all supp types & must be used with most Composition of Suppository Generally made from solid ingredients & drugs which are measured by weight. When they are mixed, melted, & poured into supp mold cavities, they occupy a V-the volume of the mold cavity. Since the components are measured by weight but compounded by Density Factor When a drug is placed in a supp base, it will displace an amount of base as a function of its density If the drug has the same density as the base, it will displace an equivalent weight of the base If the density of the drug is greater than that of the base, it will displace a proportionally smaller weight of the The Density Factor Density factors for common drugs in cocoa butter are available in standard reference texts. is used to determine how much of a base will be displaced by a drug. Aluminum Metal Molds Come in a variety of cavity sizes & with a variety of number of cavities per mold. Common sizes vary from 1-2.5 g, & common number of cavities range from 6 cavities up to 100 cavities. 2 halves of the mold are held together with either nuts or some molds have 1 centered screw Plastic Suppository Shells Come in long strips that can be torn into any number of cavities. The supp mixture is poured directly into the shell up to a mark. These disposable molds do not need any lubrication regardless of the suppository mixture. When the mixture has hardened, the plastic mold is heat sealed. Usage a Suppository Patient select 1 shell & peel the sides of the shell off to obtain supp One advantage of this type of mold: if the supp should melt, it wont run out of the mold. If the material can ongeals again, it will retain the supp shape. This type of mold is available in 1-5 g sizes, & many different colors Flexible Rubber Molds When the supp mixture has congealed in these molds, the finished supp are "pushed" out of each cavity. If the prescription does not require all of the cavities in the strip, it can be trimmed with scissors. These flexible rubber molds are ideal if the supp need to be refrigerated (shells also are suitable for this