Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. Accurately weigh or measure each ingredient. Mix the metronidazole, misoprostol, phenytoin, and potassium sorbate with the propylene glycol into a smooth paste. Incorporate the Carbopol 934P and mix well. Add approximately 85 mL of purified water and mix well. Slowly add the triethanolamine until a pH in the range of approximately 5 to 6 is obtained, mixing with a paddle with slow rotations to minimize the incorporation of air into the preparation. Add sufficient purified water to volume and mix well. Package and label.
Use: Metronidazole, misoprostol, and phenytoin topical gel has been used in the topical treatment of open ulcers and wounds.
Packaging: Package in tight, light-resistant containers.1
Labeling: Keep out of the reach of children. Use only as directed. For external use only.
Stability: A beyond-use date of up to 30 days can be used for this preparation.1
Quality Control: Quality-control assessment can include theoretical weight compared with actual weight, pH, specific gravity, active drug assay, color, texture, appearance, feel, rheologic properties, and physical observations.2
Discussion: Metronidazole (C6H9N3O3, MW 171.15) occurs as white to pale yellow, odorless crystals or as a crystal line powder. It is stable in air, but will darken upon exposure to light. It is sparingly soluble in water and alcohol.3
Misoprostol (C22H38O5, MW 382.53) is a synthetic analog of prostaglandin E1 (alprostadil) and occurs as a water-soluble, viscous liquid. The formerly available Cytotec tablets contained either 100 mcg or 200 mcg of misoprostol. The tablets also contained hydrogenated castor oil, hydroxypropyl methylcellulose, microcrystalline cellulose, and sodium starch glycolate.4
Phenytoin (C15H12N2O2, MW 252.27, 5,5-diphenylhydantoin) occurs as a white, odorless powder. It is practically insoluble in water and slightly soluble in cold alcohol, chloroform, and ether.1,5
Propylene glycol (C3H8O2) occurs as a clear, colorless, viscous, practically odorless liquid with a sweet taste, somewhat resembling glycerin. It is miscible with acetone, chloroform, 95% ethanol, glycerin, and water.6
Carbopol 934: Carbomers (Carbopols) occur as white-colored, fluffy, acidic, hygroscopic powders with a slight characteristic odor. When carbomers are dispersed in water, an acidic colloidal solution of low viscosity will form that will thicken when an alkaline material, such as triethanolamine, is added.7
Triethanolamine (TEA, trolamine) is an alkalizing and emulsifying agent. It occurs as a clear, colorless to pale yellow-colored, viscous liquid with a slight odor of ammonia. It is miscible with water, 95% ethanol, methanol, and acetone, and it is soluble in chloroform.8
Potassium sorbate (C6H7O2K, MW 150.22) occurs as a white, crystalline powder with a faint, characteristic odor. It is used as an antimicrobial (antifungal and antibacterial) preservative, generally in concentrations of approximately 0.1% to 0.2%. Potassium sorbate is soluble in water (1 g in 1.72 mL), acetone (1 g in 1,000 mL), 95% alcohol (1 g in 35 mL), and propylene glycol (1 g in 1.8 mL). It is most effective at pH values of approximately 6 and below; it loses significant efficacy above pH 6. Some loss of antimicrobial activity occurs in the presence of nonionic surfactants and with some plastics.9
Purified water is water that is obtained by distillation, ion exchange, reverse osmosis, or some other suitable process. Water has a specific gravity of 0.9971 at room temperature, a melting point of 0°C, and a boiling point of 100°C. It is miscible with most polar solvents and is chemically stable in all physical states (ice, liquid, and steam).10
REFERENCES
1. US Pharmacopeial Convention, Inc. USP Pharmacists' Pharmacopeia. 2nd ed. Rockville, MD: US Pharmacopeial Convention, Inc; 2008:775-779,1454.
2. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
3. Sweetman SC, ed. Martindale: The Complete Drug Reference. 33rd ed. London, England: Pharmaceutical Press; 2002:594-597.
4. Physicians' Desk Reference. 58th ed. Montvale, NJ: Medical Economics; 2004:3109-3111.
5. McEvoy GK. AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2008:2268-2270.
6. Owen SC, Weller PJ. Propylene glycol. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:627-628.
7. Koleng JJ, McGinity JW. Carbomer. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:111-115.
8. Goskonda SR, Lee JC. Triethanol amine. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:794-795.
9. Owen SC. Potassium sorbate. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:609-610.
10. Galichet LY. Water. In: Rowe RC, Sheskey PJ, Owen SC, eds. Handbook of Pharmaceutical Excipients. 5th ed. Washington, DC: American Pharmaceutical Association; 2006:802-806.
