Pharmaceutics Lecture 5: Suppositories PDF

Pharmaceutics Lecture 5: Suppositories Part 1 2nd stage  Suppositories Suppositories Are solid dosage forms which may contain one or more active medicaments intended for insertion into body cavities where they melt, soften, or...

Pharmaceutics Lecture 5: Suppositories Part 1 2nd stage  Suppositories Suppositories Are solid dosage forms which may contain one or more active medicaments intended for insertion into body cavities where they melt, soften, or dissolve and may exert local or systemic effects. Suppositories are commonly used rectally, vaginally and occasionally urethrally.  Advantages of Suppositories 1) Can exert local effect on rectal mucosa. 2) Can be used for systemic absorption of drugs and avoid first- pass metabolism. 3) Drug stability, avoid any gastrointestinal irritation. 4) Can be used in unconscious patients. 5) Babies or old people who cannot swallow oral medication. 6) Post operative people who cannot be administered oral medication. 7) People suffering from severe nausea or vomiting. 8) Used to promote evacuation of bowel.  Disadvantages of Suppositories 1) The problem of patient acceptability. 2) The dose of a drug required for rectal administration may be greater than or less than the dose of the same drug given orally. 3) Suppositories are not suitable for patients suffering from diarrhea. 4) The fluid content of the rectum is much less than that of the small intestine, which may affect dissolution rate. 5) Incomplete absorption may be obtained because suppository usually promotes evacuation of the bowel and the absorbing surface area of the rectum is much smaller than that of the small intestine 6) There is the possibility of degradation of some drugs by the microflora present in the rectum.  Rectal suppositories for local effect ❖ They are most frequently used. ❖ Used to relieve constipation, as laxative. Examples: 1- Glycerin suppositories , promote laxation by local irritation of the mucous membranes, due to the dehydrating effect of the glycerin on those membranes. *Dulcolax (Bisacodyl) suppositories 2-Used to relieve pain, irritation, itching, and inflammation associated with hemorrhoids and other anorectal conditions. * Hydrocortisone suppositories Anti hemorrhoidal Suppositories They frequently contain a number of components, including : 1. local anesthetics. 2. vasoconstrictors. 3. astringents. 4. analgesics. 5. soothing emollients. 6. protective agents.  Rectal suppositories for systemic actions For systemic effects, the mucous membranes of the rectum and vagina permit the absorption of many soluble drugs. Although the rectum is used frequently as the site for the systemic absorption of drugs, the vagina is not as frequently used for this purpose. Examples of drugs administered rectally in the form of suppositories for their systemic effects include : A. Relief of nausea and vomiting - ondansetron suppositories. B. Tranquilizer- prochlorperazine and chlorpromazine suppositories C. Opioid analgesia - oxymorphone HCl suppositories D. NSAID- indomethacin E. Analgesic and antipyretic- paracetamol suppository F. For migraine - ergotamine tartrate. Factors affecting the absorption of drugs from rectal suppositories The dose of a drug administered rectally may be greater than or less than the dose of the same drug given orally, depending on such factors:  Physiologic factors i. Colonic contents: A drug will obviously have greater opportunity to make contact with the absorbing surface of the rectum and colon in an empty rectum. ii. Circulation route: bypass the portal circulation during their first pass into the general circulation, thereby enabling drugs otherwise destroyed in the liver to exert systemic effect. iii. pH and lack of buffering capacity of the rectal fluids: because rectal fluids are essentially neutral in pH (7.2-7.4) and have no effective buffer capacity, the form in which the drug is administered will not generally be chemically changed by the environment.  Physicochemical factors i. The relative solubility of the drug in lipid and in water: the more drug the base contains, the more drug will be available for absorption. ** ❑ If drug concentration in the intestinal lumen is above a certain amount, the rate of absorption is not changed by further increase of the drug. i. The particle size of a dispersed drug: the smaller the particle, the greater the surface area, the more readily the dissolution of the particle, and the greater the chance for rapid absorption. ❖ It is preferable to avoid a too fine particle size because of the high increase of the viscosity of the melted excipient that can result from the use of excessively small particles and possible difficulties in flow during production. iii. Physicochemical factors of the base include its ability to melt, soften, or dissolve at body temperature, its ability to release the drug substance, and its hydrophilic or hydrophobic character. If the base interacts with the drug to inhibit its release, drug absorption will be impaired or even prevented. Also, if the base irritates the mucous membranes of the rectum, it may initiate a colonic response and induce a bowel movement, eliminating the possibility of complete drug release and absorption. **Lipid–Water Solubility The lipid–water partition coefficient of a drug is an important consideration in the selection of the suppository base and in anticipating drug release from that base. A lipophilic drug that is distributed in a fatty suppository base (in low concentration) has less tendency to escape to the surrounding aqueous fluids than a hydrophilic substance in a fatty base.  SUPPOSITORY BASES The base should remain solid at room temperature, but, It must be melting, softening, or dissolving at body temperature to release its drug for absorption. No chemical and/or physical interactions between the medicinal agent and the suppository base, which may affect the stability and/or bioavailability of the drug. Long acting or slow release suppositories have also been prepared. Morphine sulfate in slow release suppositories is prepared in a base that includes a material such as alginic acid, which will prolong the release of the drug over several hours. Properties of the ideal suppository base 1. Non-toxic, non- irritating to sensitive and inflamed tissues. 2. Inert and compatible with medicaments. 3. Not deteriorated or contaminating the drug during storage. 4. Easily manufactured by compression or molding. 5. Dissolve or disintegrate in mucous secretions or melt quickly at body temperature to allow the release of medicament. 6. Remain molten for a sufficient period of time to allow pouring into molds. 7. Solidify rapidly to minimize sedimentation of dispersed solids. 8. Contract on cooling to allow easy withdrawal of the suppository from the mold. 9. Has wetting and emulsifying properties. 10. Stable on storage, keeps its shape during storage or handle does not change color, odor and drug release pattern.