DRUG DOSAGE FORMS & DELIVERY SYSTEMS


Suppositories

Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects. The derivation of the word suppository is from the Latin supponere, meaning “to place under,” as derived from sub (under) and ponere (to place).

Rectal Suppositories

Rectal suppositories are usually about 32 mm (1.5 in.) long, are cylindrical, and have one or both ends tapered. Some rectal suppositories are shaped like a bullet, a torpedo, or the little fi nger. Depending on the density of the base and the medicaments in the suppository, the weight may vary. Adult rectal suppositories weigh about 2 g when cocoa butter (theobroma oil) is employed as the base. Rectal suppositories for use by infants and children are about half the weight and size of the adult suppositories and assume a more pencillike shape.

Urethral Suppositories

Suppositories for urethral administration tend to be thinner and tapered, often about 5 mm in diameter. They have been used in the treatment of local infections, and a much smaller urethral suppository has been introduced for the administration of alprostadil in the treatment of erectile dysfunction.

Vaginal Suppositories

These preparations are employed principally to combat infections in the female genitourinary tract, to restore the vaginal mucosa to its normal state, and for contraception. The usual pathogenic organisms are Trichomonas vaginalis, Candida (Monilia) albicans or other species, and Haemophilus vaginalis. Among the anti-infective agents in commercial vaginal preparations are nystatin, clotrimazole, butoconazole nitrate, terconazole, and miconazole (antifungals) and triple sulfas, sulfanilamide, povidone iodine, clindamycin phosphate, metronidazole, and oxytetracycline (antibacterials). Nonoxynol-9, a spermicide, is employed for vaginal contraception. Estrogenic substances such as dienestrol are found in vaginal preparations to restore the vaginal mucosa to its normal state.

The most commonly used base for vaginal suppositories consists of combinations of the various molecular weight polyethylene glycols. To this base is frequently added surfactants and preservative agents, commonly the parabens. Many vaginal suppositories and other types of vaginal dosage forms are buffered to an acid pH usually about 4.5, consistent with the normal vagina. This acidity discourages pathogenic organisms and provides a favorable environment for eventual recolonization by the acid- producing bacilli normally found in the vagina. The polyethylene glycol–based vaginal suppositories are water miscible and are generally suffi ciently fi rm for the patient to handle and insert without great diffi culty. However, to make the task easier, many manufacturers provide plastic insertion devices that are used to hold the suppository or tablet for proper placement within the vagina.

Packaging and Storage

Glycerin suppositories and glycerinated gelatin suppositories are packaged in tightly closed glass containers to prevent a change in moisture content. Suppositories prepared from a cocoa butter base are usually individually wrapped or otherwise separated in compartmented boxes to prevent contact and adhesion. Suppositories containing light-sensitive drugs are individually wrapped in an opaque material such as a metallic foil. In fact, most commercial suppositories are individually wrapped in either foil or plastic. Some are packaged in a continuous strip, separated by tearing along perforations. Suppositories are also commonly packaged in slide boxes or in plastic boxes.

Because suppositories are adversely affected by heat, it is necessary to maintain them in a cool place. Cocoa butter suppositories must be stored below 30°C (86°F), and preferably in a refrigerator (2°C to 8°C, or 36°F to 46°F). Glycerinated gelatin suppositories can be stored at controlled room temperature (20°C to 25°C, or 68°F to 77°F).

Suppositories made from a base of polyethylene glycol may be stored at usual room temperatures. Suppositories stored in high humidity may absorb moisture and tend to become spongy, whereas suppositories stored in places of extreme dryness may lose moisture and become brittle.

FINISHED PRODUCT
Manufacture:
Manufactured both on a small scale in batches of 10-20 and on a (semi) automatic scale in batches up to 20,000 per hour.
QUALITY CONTROL
Control Parameters of Suppositories:
  1. Appearance
  2. Weight
  3. Disintegration
  4. Melting (dissolution) behavior
  5. Mechanical strength (tablet crushing strength tester)
  6. Content of active ingredient
  7. Release
FORMULATION OF VAGINAL DOSAGE FORMS
  • These are mostly prepared with glycerol-gelatin bases, since this mixture is well-tolerated
  • PEGs are less common since they are said to promote irritation.