Drug Release and Skin Irritancy of Poloxamer Gel Containing Kojic Acid

코지산을 함유한 폴록사머 겔 제제의 약물방출 및 피부자극성

  • Park, Eun-Woo (College of Pharmacy, Chung-Ang University) ;
  • Cho, Seong-Wan (College of Pharmacy, Chung-Ang University) ;
  • Kim, Dong-Sup (Dept. of Clinical Pharmacology, National Institute of Toxicology Center) ;
  • Choi, Ki-Hwan (Dept. of Clinical Pharmacology, National Institute of Toxicology Center) ;
  • Choi, Young-Wook (College of Pharmacy, Chung-Ang University)
  • 박은우 (중앙대학교 약학대학) ;
  • 조성완 (중앙대학교 약학대학) ;
  • 김동섭 (국립독성연구소 약효약리과) ;
  • 최기환 (국립독성연구소 약효약리과) ;
  • 최영욱 (중앙대학교 약학대학)
  • Published : 1998.09.20

Abstract

Low toxicity, reverse thermal gelation and high drug loading capabilities suggest that poloxamer 407 gels have great potential as a topical drug delivery system. Kojic acid (KA) is an antimelanogenic agent which has been widely used in cosmetics to whiten the skin color. However, it has the drawbacks of skin irritancy due to its acidic pH. Poloxamer gels of different polymer contents were formulated to overcome the problem and compared to the cream type formulations of either w/o/w multiple emulsion cream or o/w type emulsion cream. Using Franz diffusion cells mounted with a synthetic cellulose membrane (MWCO 12,000), drug release characteristics of the formulations were evaluated by the HPLC assay of KA concentration in the receptor compartment of pH 7.4 phosphate buffered saline solutions. Drug release from w/o/w multiple emulsion cream was controlled by oil membrane, showing the apparent zero order release kinetics. The KA release from the poloxamer gels was also controlled by the gel matrix, showing that drug release increased linearly as KA contents increase, but decreased exponentially as the polymer contents increase. In the skin irritancy test, the primary irritancy index(PII) of poloxamer gel base was lower than those of multiple emulsion cream base and o/w cream. Depending on KA contents or polymer contents in the gel. PH values in poloxamer gels were ranged from 1.3 to 2.0, which are interpreted as low or negligible irritation on skin. There was a good correlation between the log value of flux in drug release and PII value in skin irritation. It was possible to conclude that the poloxamer gels containing KA might be a good candidate for an antimelanogenic topical delivery system by virtue of the controlled release of the drug and the reduced skin irritancy.

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