title: Influence of 6-ketocholestanol on skin permeation of 5-aminolevulinic acid and evaluation of chemical stability.
abstract: The ability of 6-ketocholestanol to increase the skin permeation of the prodrug aminolevulinic acid (5-ALA) was investigated. 6-Ketocholestanol was incorporated together with 5-ALA in four different formulations. Preparations used were a liquid solution/suspension of 5-ALA in buffer, 5-ALA in phospholipid liposomal formulations with and without gelating agent, and finally, a complex cream formulation also including phospholipids. Standard diffusion experiments of 5-ALA using Franz-type diffusion cells and porcine skin were performed. Drug stability was monitored by analyzing the 5-ALA content in the different formulations over time and viewing the preparation for microbial contamination. The analysis of 5-ALA as a nonfluorescent probe was performed after chemical reaction, leading to a fluorescent derivative. The 5-ALA permeation through porcine skin was increased threefold by 6-ketocholestanol in the cream formulation. The chemical stability of 5-ALA in the tested formulations was in the range of about 33 to 72% after an observation period of 28 days. After that time point microbial stability was no longer evident for formulations 2 and 3. Formulation 1 could be observed until day 34, and only formulation 4 showed a microbial stability over the whole observation period of 42 days.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, Centre of Pharmacy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Barbara Gabriele
authors.initials: BG
authors.lastname: Auner
authors.forename: Elke
authors.initials: E
authors.lastname: Petzenhauser
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenta
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D066298:In Vitro Techniques; D007653:Ketocholesterols / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013552:Swine
chemical_list: D007653:Ketocholesterols; C063833:6-ketocholestanol; D000622:Aminolevulinic Acid