DDS Lec Module 2.4 Suppositories PDF

SUPPOSITORIES INSERTS AND STICKS SUPPOSITORIES Solid dosage form in which one or more API’s are dispersed in a suitable base and molded into a suitable shape Are solid dosage forms intended for insertion into the body orifices where they melt, soften, or dissolve and exert localized...

SUPPOSITORIES INSERTS AND STICKS SUPPOSITORIES Solid dosage form in which one or more API’s are dispersed in a suitable base and molded into a suitable shape Are solid dosage forms intended for insertion into the body orifices where they melt, soften, or dissolve and exert localized or systemic effects Reasons in using Suppositories 1. promote defecation 2. introduce drugs into the body 3. treat anorectal disease 3 Advantages of Suppositories Avoid first pass effect Avoid gastric degradation Administer larger doses of drugs than oral medication Administer drugs that can cause irritation to GI mucosa Administer unpleasant tasting or smelling drugs  Advantages of Suppositories Useful in children, refuse oral medication and fear of injection For patient experiencing nausea and vomiting when patient is unconscious Presence of disease in upper GIT that may interfere drug absorption Rapid drug effect systematically (alternate to injection) Disadvantages of Suppositories Lack of flexibility in dosage resulting to underuse and lack of availability Made by demand, it is expensive They are safe but effectiveness varies in different factors Narrow therapeutic margin drugs cannot be interchanged without risk of toxicity Bullet shape suppository after insertion can leave at anorectal site, should not be used at bedtime Disadvantages of Suppositories Absorbing surface area of rectum is much smaller than that of the small intestine Fluid content of the rectum is much less than that of the small intestine which may affect dissolution rate Possibility of degradation of some drugs by the microflora present in the rectum Greater dose for rectal route than oral route  LOCAL ACTION Once inserted , it will melt, soften, or dissolve, distributing its medicaments to the tissue of the region. RECTAL VAGINAL URETHRAL ▪ Constipation Contraceptives Antibacterial ▪ Relive pain, (nonoxynol 9) Local anesthetics irritation, itching and Antiseptic in feminie for urethral inflammation hygiene examination associated with Combat invading hemorhoids and pathogen anorectal conditions (Trichomonacides, ▪ Laxative (glycerin) Antifungal, Antibiotics, Anti-infectives)  Systemic Action Use/Indication/Therapeutic Drug (Active in suppository form) Class Ondansetron nausea and vomiting Prochlorperazine and nausea, vomiting Chlorpromazine tranquilizers Oxymorphone and morphine opioid analgesic Ergotamine tartrate Migraine Indomethacin NSAID Opigesic supp. (Paracetamol) Analgesic-antipyretic Factors affecting the absorption of drugs from rectal suppositories PHYSICOCHEMICAL PHYSIOLOGIC FACTORS FACTORS Circulation route Lipid-water Solubility pH of Rectal fluids Particle size Colonic content Nature of base Factors affecting the absorption of drugs from rectal suppositories Physiologic Factors Circulation route Drugs absorbed in the rectum bypass the first pass effect in the liver instead of being absorbed into the general circulation Lymphatic circulation also assist in the absorption of rectally administered drug Factors affecting the absorption of drugs from rectal suppositories Physiologic Factors pH and Lack of buffering capacity of the rectal fluids Rectal fluids are essentially neutral in pH and have no effective buffer capacity, the form in which the drug is administered will not generally be chemically changed by the rectal environment. Factors affecting the absorption of drugs from rectal suppositories Physiologic Factors Colonic content It is more effective for a drug to absorbed systemically in an empty rectum than from one that is distended with fecal Diarrhea, tissue dehydration can influence the rate and degree of absorption at the rectal site Factors affecting the absorption of drugs from rectal suppositories Physicochemical Factors Lipid-water solubility a lipophilic drug that is distributed in a fatty suppository base in low concentration has less of a tendency to be released into the body fluid, than in a fatty base Particle size Smaller particle size the more readily the dissolution of the particle and the greater chance for rapid absorption Factors affecting the absorption of drugs from rectal suppositories Physicochemical Factors Nature of the base Base must be capable of melting, softening or dissolving to release its absorption If the base interacts with the drug to inhibit its release , drug reaction will be impaired or prevented Ideal Suppository Bases Physically and Chemically and Chemically stable physically inert Nonirritating Compatible with a Nontoxic variety of drug Nonsensitizing Stable during storage Esthetically acceptable(odor and appearance)  Classification of Bases Fatty or oleaginous Water soluble or Miscellaneous Water miscible Most frequently used Glycerinated Gelatin Mixture of oleaginous Cocoa butter Polyethylene glycol and Water soluble Hydrogenated fatty and water miscible acids of vegetable oil Polyoxyl 40 stearate (palm kernel oil and cottonseed oil) Fat based with glycerin and high MW fatty acids (palmitic and stearic acids; glyceryl monosterate and glyceryl monopalmitate) Fatty and Oleaginous Base Cocoa Butter o Theobroma cacao o Melts at 30-36°C o Ideal rectal suppository base o Disadvantage: exhibit polymorphism=> crystals o Must be slowly and evenly melted in water bath to avoid crystallization o Phenol and chloral hydrate-lowers melting pt o Cetyl esters wax (20%) or beeswax (4%)  WITEPSOL BASES – triglycerides of saturated fatty acids (lauric acid) -triglycerites of saturated fatty acids C12-C18 with varied portion of corresponding partial glycerides) WECOBEE BASES – triglycerides derived from coconut oil FATTIBASE® - triglycerides from palm, palm kernel, and coconut oils with self emulsifying glyceryl monostearate and polyoxyl stearate Water soluble and Water Miscible Bases Glycerinated gelatin Most frequently used in vaginal suppositories Gelatin (20%) glycerin (70%) Medication (10%) Tends to absorb moisture, has dehydrating effect and irritates tissue upon insertion (moist prior to insertion) Urethral: Gelatin (60%) glycerin (20%) Medication (20%)  Do not melt at body Do not leak from orifices temperature but rather PEG less than 20% dissolved slowly in the water should be dipped body’s fluid in water prior to use  Formulation Consideration a. Nature and form of the active ingredients b. Physical state, particle dimensions and specific surface of the products c. Solubility of the drug in various bases d. Presence or absence of adjuvants added to the Active Principles e. Nature and type of dosage form in which the active principles is incorporated f. Pharmaceutical procedures used in the preparation of the dosage forms Preparation of Suppositories Molding from a melt - most frequently used (fusion method) Hand rolling and shaping - oldest and simplest method, by rolling the suppository into the desired shape. The mass is then rolled into a cylindrical rod of desire length and diameter Compression - cold mass of the base containing the drug is compressed into suppositories by using compression into the desired shape.  Molding from a melt ▪ Melting of the base ▪ Incorporation of any required medicament ▪ Pouring the melt in the molds ▪ Allowing the melt to cool and congeal to suppositories ▪ Removing the formed suppositories from the mold ▪ The molds may be made up of stainless steel, aluminum, brass, plastic ▪ Lubricant- necessary with glycerinated gelatin (mineral oil)  Packaging and Storage Cocoa Butter Glycerinated PEG gelatin Individually wrapped Tightly closed Tightly closed Separate container container compartmentalized box Stored below 30C Controlled room Usual room refrigerated temperature (20-25) temperature Light sensitive drugs- individually wrapped, opaque materials like metallic foil or plastic Stored in high humidity- absorb moisture tends to become spongy Stored in extreme dryness may lose moisture and become brittle Urethral Suppository MUSE (ALPROSTADIL) urethral microsuppository A single-use medicated transurethral system for the delivery of alprostadil to the male urethra Treatment of Erectile dysfunction http://muserx.com/hcc/about-muse/how-to-use-muse.aspx  VAGINAL INSERT Vaginal tablet Adv: easy to manufacture; more stable; less messy Usually ovoid packed with inserter Prepared by tablet compression Lactose - filler/diluent Starch - disintegrant Polyvinylpyrrolidone - Dispersing agent Magnesium Stearate - lubricant Capsules of gelatin coating (vagina and rectum) STICKS Medicated sticks Administering topical drugs Cylindrical in shape ranging from 5 to 25g Packed in an applicator tube for topical administration and the applicator can be adjusted to continually exposed new fresh sticks How to prepare Same as preparing supp except that melt is poured into the administering device or tube Local anesthetics, sunscreens, oncology products, antiviral and antibiotics