US Pharm. 2012;37(12):43-44.
Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Mix the spironolactone, niacinamide, and cimetidine with the alcohol. Add the Carbopol 940 and mix well. Then add about 40 mL of purified water and mix well. Dropwise, add the trolamine and mix until thickened. Add sufficient purified water to final weight and mix well.
Use: This formulation has been used in the treatment of acne.1-3
Packaging: Package in tight, light-resistant containers.
Labeling: For external use only. Keep out of reach of children. Store and keep away from flame and heat. Discard after ____ [time period].
Stability: A beyond-use date of up to 30 days may be used for this preparation.4
Quality Control: Quality-control assessment may include theoretical weight compared with actual weight, pH, specific gravity (SG), active drug assay, color, texture–surface, texture–spatula spread, appearance, feel, rheologic properties, and physical observations.5
Discussion: Spironolactone (Aldactone, C24H32O4S, MW 416.57) occurs as a light cream-colored to light tan, crystalline powder. It has a faint to mild mercaptan-like odor and is stable in air. It is soluble in alcohol and practically insoluble in water. It is an antihypertensive and a potassium-sparing diuretic. Spironolactone is used to manage edema and hypertension and (topically) to treat acne. It loses not more than 0.5% of its weight upon drying.4
Niacinamide (C6H6N2O, MW 122.12, nicotinamide) occurs as a white, crystalline powder that is odorless or practically odorless and has a bitter taste. It is freely soluble in water and alcohol and is soluble in glycerin. A 5% aqueous solution has a pH of 6.0 to 7.5. Niacinamide melts at 128°C to 131°C and loses not more than 0.5% of its weight upon drying. It should be stored in a tight container.4
Cimetidine (Tagamet, C10H16N6S, MW 252.34) occurs as a white to off-white, crystalline powder. It may be odorless or have a slight mercaptan odor. It is soluble in alcohol and in polyethylene glycol 400, sparingly soluble in isopropyl alcohol, and slightly soluble in water. It melts between 139°C and 144°C and loses not more than 1.0% of its weight upon drying. Cimetidine is a histamine2 blocker used in the short-term treatment of ulcers and gastroesophageal reflux, acid indigestion, and heartburn; it is also used topically in the treatment of acne.4
Carbopol 940 is a synthetic, high molecular weight (MW) polymer composed of acrylic acid cross-linked with either allyl sucrose or allyl ethers of pentaerythritol. It occurs as a white-colored, fluffy, acidic, hygroscopic powder with a slight characteristic odor. Its MW is approximately 4 × 106. The pH of a 0.5% to 1.0% dispersion ranges from 2.5 to 3.5. Carbopol 940 has a tapped density of 1.4 g/mL. It decomposes at 260°C and has an average particle-size distribution of 2 to 7 µm. It is soluble in water and (after neutralization) in 95% ethanol and glycerin. When carbomers are dispersed in water, an acidic colloidal solution of low viscosity forms that will thicken when an alkaline material, such as triethanolamine, is added. Maximum viscosity generally can be obtained in a pH range of 6 to 11. The gel should be protected from light and contain an antimicrobial preservative.6
Alcohol (ethyl alcohol, ethanol, grain alcohol, C2H5OH, MW 46.07) is a clear, colorless, mobile, and volatile liquid with a slight, characteristic odor and a burning taste. Alcohol USP refers to 95% ethanol; dehydrated alcohol refers to 99.5% alcohol. Alcohol’s SG is between 0.812 and 0.816, and its boiling point is 78.15°C. Alcohol is miscible with glycerin and water and should be stored in a cool place.7
Trolamine (TEA, triethanolamine) is an alkalizing and emulsifying agent. Occurring as a variable mixture of alkanolamines, it is a clear, colorless to pale yellow-colored, viscous liquid with a slight ammoniacal odor. Its SG is about 1.120 to 1.128 g/mL, and it has a pH of 10.5 in a 0.1-N aqueous solution. Trolamine is highly hygroscopic, melts at 20°C to 21°C, and boils at 335°C. It is miscible with water and 95% ethanol. When exposed to air and light, it may turn brown; at temperatures below 15°C, it may stratify (this can be corrected by warming and mixing). Trolamine should be stored in an airtight container, protected from light, in a cool place.8
1. Rathnayake D, Sinclair R. Use of spironolactone in dermatology. Skinmed. 2010;8:328-332.
2. Surjana D, Damian DL. Nicotinamide in dermatology and photoprotection. Skinmed. 2011;9:360-365.
3. Schmidt JB, Spona J. Topical cimetidine treatment of acne. Z Hautkr. 1986;61:1065-1072.
4. U.S. Pharmacopeia 35/National Formulary 30. Rockville, MD: US Pharmacopeial Convention, Inc; 2012:334-386,1110,1132,1146,2665,4044,4680.
5. Allen LV Jr. Standard operating procedure for performing physical quality assessment of ointments/creams/gels. IJPC. 1998;2:308-309.
6. Draganoiu E, Rajabi-Siahboomi A, Tiwari S. Carbomer. In: Rowe RC, Sheskey PJ, Cook WG, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:118-123.
7. Fenton ME. Alcohol. In: Rowe RC, Sheskey PJ, Cook WG, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:19-22.
8. Goskonda SR. Triethanolamine. In: Rowe RC, Sheskey PJ, Cook WG, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 7th ed. Washington, DC: American Pharmaceutical Association; 2012:865-867.
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