Influence of 6-ketocholestanol on skin permeation of 5-aminolevulinic acid and evaluation of chemical stability.
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.
Auner
Barbara Gabriele
BG
Institute of Pharmaceutical Technology and Biopharmaceutics, Centre of Pharmacy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Petzenhauser
Elke
E
Valenta
Claudia
C
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
D007653:Ketocholesterols; C063833:6-ketocholestanol; D000622:Aminolevulinic Acid