Preparation of Griseofulvin for Topical Application Using N-Methyl-2-pyrrolidone

• Published in: Biological & pharmaceutical bulletin Vol. 23; no. 11; pp. 1341 - 1345
• Main Authors: FUJII, Makiko, BOUNO, Masayo, FUJITA, Sachie, YOSHIDA, Minako, WATANABE, Yoshiteru, MATSUMOTO, Mitsuo
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.11.2000; Maruzen; Japan Science and Technology Agency
• Subjects: Administration, Topical; Animals; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Antipruritics - pharmacokinetics; Biological and medical sciences; emulsion; Emulsions; Excipients; General pharmacology; griseofulvin; Griseofulvin - administration & dosage; Griseofulvin - pharmacokinetics; In Vitro Techniques; Medical sciences; Menthol - pharmacokinetics; N-methyl-2-pyrrolidone; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphatidylcholines; Pyrrolidinones - chemistry; Skin Absorption - drug effects; Soybean Oil; Suspensions; Swine; Swine, Miniature; topical application; Pharmaceutical technology; 3-p-Menthanol; Oil water emulsion; Biological transport; Permeation; Epidermis; Drug carrier; Griseofulvin; In vitro; Pig; Percutaneous route; Vertebrata; Mammalia; Animal; Dosage form; Phosphatidylcholine; Skin; Absorption enhancer; Artiodactyla; Pyrrolidone derivatives; Derm; Diffusion; Soybean oil; Ungulata
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.23.1341

We attempted to prepare a new griseofulvin formulation for topical application using N-methyl-2-pyrrolidone (NMP). Griseofulvin dissolves poorly in both water and oil, but dissolves in NMP to a concentration of about 100 mg/ml. A soybean oil-water emulsion with soybean lecithin and NMP as emulsifier and co-solvent, respectively, was prepared using a Microfluidizer, a high-pressure homogenizer. The size of the droplets in emulsion was about 200 nm, and the emulsion was stable for over 3 months. The skin permeation of griseofulvin through Yucatan micropig skin was studied in vitro using vertical type cells under donor phase open conditions. The permeation of griseofulvin from the NMP-water mixture (0-40%) into the skin tended to increase with increasing NMP concentration, although this finding was not statistically significant. Permeation from emulsion (oil phase, 20%; NMP 10-40%) was significantly higher than that from the water-NMP mixture. Permeation from the oil-NMP mixture was highest among the formulations investigated, and permeation from emulsion under donor phase closed conditions was significantly lower than that under open conditions. We believe that the evaporation of water from the emulsion after application to the skin was an important factor in skin permeation enhancement. When the emulsion containing 3% l-menthol was applied, a sufficient skin concentration (47μg/cm3 in dermis) was obtained.