ALTHOUGH UNIONIZED DRUGS ARE MORE READILY PARTITION OUT OF THE WATER MISCIBLE BASES (GLYCERINATED GELATIN and PEG). THESE BASES TEND TO DISSOLVE SLOWLY, WHICH DELAYS THE RELEASE OF THE DRUG.
ALGINIC ACID – INCORPORATED IN LA OR SLOW RELEASE SUPPOSITORIES, TO PROLONG DRUG RELEASE FOR SEVERAL HOURS.
ANTIFUNGAL FOR VULVOVAGINAL CANDIDIASIS (Moniliasis) See page 326 table 12.2
NUMBER 0 – FOR CHILDREN, AND FOR OTIC AND NASAL USE NUMBERS 1,2, AND 3 – FOR RECTUM NUMBER 4 – VAGINAL PESSARY A and B – ARE NASAL BOUGIES
THE IDEAL SUPPOSITORY SINCE IT MELTS JUST BELOW NORMAL BODY TEMP., YET IS SOLID AT ROOM TEMP.
Chapter 12:SUPPOSITORIESandINSERTSBy:Asst. Prof. MA. LOURDES L. MOJARES, R. Ph.School of PharmacyCEU Manila
SUPPOSITORIES Solid dosage forms intended for insertion into the body orifices where it; 1. melt 2. soften 3. dissolve and exert localized or systemic effects
TYPES OF SUPPOSITORIESRECTAL SUPPOSITORIES About 32 mm (1 ½ inches) in length, cylindrical, one or both ends tapered and some are bullet shaped Adult rectal suppositories weigh about 2 grams when cocoa butter is used as a base Intended for both local and systemic actions
RECTAL SUPPOSITORIESFOR LOCAL EFFECT Used to relieve constipation, as laxative. Examples: Glycerin suppositories Dulcolax (Bisacodyl) suppositories
RECTAL SUPPOSITORIESFOR LOCAL EFFECT Used to relieve pain, irritation, itching, and inflammation associated with hemorrhoids and other anorectal conditions Examples: Hydrocortisone suppositories Mesalamine suppositories
Systemic effects via rectal route: ADVANTAGES1. Drugs are not destroyed or inactivated by the pH or enzymatic activity of the GIT2. GI irritation is avoided3. Bypass the liver4. Convenient for administration of drugs to patients who are unable to swallow5. Effective route in treatment of patients with vomiting
Factors affecting the absorption of drugs from rectal suppositories Physiologic Physicochemical factors factors Colonic content Lipid-water Circulation route solubility pH and Lack of Particle size buffering capacity Nature of the base of the rectal fluids
COLONIC CONTENTFor Systemic drug effect, absorption isgreater in a rectum that is void/empty.Diarrhea, Fecal matter Slow down rectalTumor growth drug absorptionTissue dehydration
pH and LACK OF BUFFERING CAPACITY OF THE RECTAL FLUIDS It is preferred to incorporate the “ionized” salt form of the drug, to maximize bioavailability. COCOA BUTTER – melts rapidly at normal body temperature (due to its immiscibility with fluids), it fails to release fat-soluble drugs readily.
PHYSICO-CHEMICAL FACTORS OF THE DRUG AND THE BASE Lipid – Water Solubility 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.
PHYSICO-CHEMICAL FACTORS OF THE DRUG AND THE BASE Lipid – Water Solubility A lipophilic drug that is distributed in a fatty base (at low concentration) has less tendency to be released into the body fluid, than a hydrophilic drug in a fatty base.
PHYSICO-CHEMICAL FACTORS OF THE DRUG AND THE BASE Particle Size The smaller the particle size, the greater the surface area, the more readily the dissolution of the particle, the greater the chance for rapid absorption.
PHYSICO-CHEMICAL FACTORS OF THE DRUG AND THE BASE Nature of the Base If the base interacts with the drug to inhibit its release, drug absorption will be impaired or prevented.
PHYSICO-CHEMICAL FACTORS OF THE DRUG AND THE BASE Nature of the Base If the base irritates the mucous membranes of the rectum, it may prompt bowel movement, thus eliminating the chance for complete bowel movement and absorption
VAGINAL SUPPOSITORIESAlso called “ PESSARY / PESSARIES” Globular, oviform, or cone shapedWeigh about 5 grams when cocoa butter is used as the base Employed mainly as contraceptives, antiseptics in feminine hygiene, and as specific agents to combat invading pathogen More widely compounded than vaginal inserts
VAGINAL INSERTS / TABLETS Morewidely used than vaginal suppositories. Easierto manufacture, more stable and are less messy. Ovoid shaped Package includes a plastic inserting device.
VAGINAL INSERTS Prepared by compression methods Contain lactose (filler); starch (disintegrant); PVP (dispersing agent); magnesium stearate (lubricant) Some may come in a form of gelatin capsules of the drug, which is released intravaginally.
VAGINAL INSERTS: EXAMPLESPRODUCT NAME GENERIC NAME CATEGORYSEMICID VAGINAL NONOXYNOL - 9 NON-SYSTEMICCONTRACPTIVE REVERSIBLE BIRTHINSERTS CONTROLENCARE NONOXYNOL - 9 NON-SYSTEMICCONTRACEPTIVE REVERSIBLE BIRTHINSERTS CONTROL
URETHRAL SUPPOSITORIES Also known as “BOUGIES” Slender, pencil-shaped May be antibacterial or a local anesthetic preparative to urethral examination
URETHRAL SUPPOSITORIES1. Male Urethral suppository – About 3 to 6 mm in diameter and approx. 140 mm in length; weigh about 4 grams when cocoa butter is used as the base2. Female Urethral suppository – About 70 mm in length and weigh about 2 grams when cocoa butter is used as the base
Alprostadil Urethral Microsuppository (MUSE) A single-use medicated transurethral system for the delivery of the drug, Alprostadil to the male urethra. Indicated for the treatment of erectile dysfunction (ED)
SUPPOSITORY BASESI. BASES THAT MELT –FATTY OR OLEAGINOUS BASES COCOA BUTTER –Theobroma oil Melts at 300C to 360C Good base for rectal suppositories but less ideal for vaginal and urethral suppositorries. Exhibits polymorphism Its melting can be lowered by certain drugs (e.g. phenol and chloral hydrate)
COCOA BUTTER (Theobroma cacao) CETYL ESTERS WAX (20 %) BEESWAX (4 %) May be added to compensate for the softening effect of added substance to Cocoa butter.
SUPPOSITORY BASESI. BASES THAT MELT –FATTY OR OLEAGINOUS BASES WITEPSOL BASES – triglycerides of saturated fatty acids C12 to C18. WECOBEE BASES – triglycerides derived from coconut oil FATTIBASE® - triglycerides from palm, palm kernel, and coconut oils with self emulsifying glyceryl monostearate and polyoxyl stearate
SUPPOSITORY BASESII. WATER SOLUBLE AND WATER MISCIBLE BASES PEG POLYMERS Use combination of PEG polymers of varying molecular weights: PEG 400 –liquid PEG 1000 – semisolid
SUPPOSITORY BASESII. WATER SOLUBLE AND WATER MISCIBLE BASES1. PEG POLYMERS PEG 1500 to 1540 – fairly firm semisolids PEG 4000 to 6000 – wax-like These bases “do not leak” from the orifice.
SUPPOSITORY BASESI2. GLYCERINATED GELATIN Frequentlyused base in vaginal suppositories. Suppositories (using this base) should be moistened first with water to avoid irritation to the tissue upon insertion.
SUPPOSITORY BASESIII. MISCELLANEOUS BASES Mixtures of oleaginous and water-soluble or water-miscible materials Hold water or aqueous solutions and are said to be hydrophilic
PREPARATION OF SUPPOSITORIES1. HAND ROLLING The oldest and simplest method of suppository preparation. Method of choice when only a few suppositories are to be prepared in a cocoa butter base.
HAND ROLLING METHODIt has the advantage of avoiding thenecessity of heating the cocoabutter.A plastic-like mass is prepared by“triturating” grated cocoa butterand active ingredients in a mortar.
HAND ROLLING METHODThe mass is formed into a ball in thepalm of the hands, then rolled into auniform cylinder with a large spatulaor small flat board on a pill tile.The cylinder is then cut into theappropriate number of pieces whichare rolled on one end to produce aconical shape.
COMPRESSION MOLDING METHODA method of preparing suppositoriesfrom a mixed mass of gratedsuppository base and medicamentswhich is forced into a specialcompression mold.
FUSION MOLDING METHODThe mixture is removed from theheat and poured into a suppositorymold.When the mixture has congealed, thesuppositories are removed from themold.
FUSION MOLDING: steps1. Melting the base2. Incorporating any required medicaments3. Pouring the melt into molds4. Allowing the melt to cool and congeal to suppositories5. Removing the formed suppositories
PACKAGING and STORAGE of SUPPOSITORIES1. COCOA BUTTER BASED SUPPOSITORIES Individually wrapped Kept refrigerated
PACKAGING and STORAGE of SUPPOSITORIES2. GLYCERIN SUPPOSSITORIES AND GLYCERINATED GELATIN BASED SUPPOSITORIES Packaged in a tightly closed containers Stored at temperature below 35°F Can be stored at controlled room temperature (200C to 250C)
PACKAGING and STORAGE of SUPPOSITORIES3. PEG BASED SUPPOSITORIES Stored at usual room temperature NO REFRIGERATION required