In vitro evaluation of the release of albuterol sulfate from polymer gels: effect of fatty acids on drug transport across biological membranes.
In this investigation, the diffusion of the beta 2 agonist albuterol sulfate (ABS) across several membranes (cellulose, hairless mouse skin, human cadaver skin) from polymer gels was studied, and the effects of several fatty acids on drug permeation through skin were evaluated. The results were then used to predict whether transdermal delivery would be appropriate for ABS. All in vitro release studies were carried out at 37 degrees C using modified Franz diffusion cells. In preliminary studies, ABS release through cellulose membranes was studied from two polymeric gels, Klucel (hydroxypropylcellulose) and Methocel (hydroxypropylmethylcellulose). Three polymer concentrations were used for each gel (0.5%, 1.0%, and 1.5%). From these experiments, Klucel 0.5% was selected as the optimal formulation to study ABS diffusion across hairless mouse skin. Experiments were conducted to evaluate the effects of capric acid, lauric acid, and myristic acid as penetration enhancers. The results suggested that lauric acid preferentially enhanced ABS diffusion compared to the other fatty acids studied, and follow-up studies were done to evaluate the release through human cadaver skin from a donor containing 2% ABS and lauric acid in 0.5% Klucel. These experiments showed that a 2:1 (lauric acid:ABS) molar ratio gave the best ABS release rates. The release rate across human cadaver skin declined slowly over 24 hr, and an average flux over 24 hr of approximately 0.09 mg/hr cm2 was measured. Using this value as a steady-state flux, extrapolations predicted that transdermal delivery can be used to maintain therapeutic ABS plasma levels (6-14 ng/mL) for extended periods. The results of this research suggest that ABS is a good candidate for transdermal drug delivery.
Chisty
Mohammed Nasser Ali
MN
Division of Pharmaceutics and Industrial Pharmacy, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island University, Brooklyn, NY 11201, USA.
Bellantone
Robert A
RA
Taft
David R
DR
Plakogiannis
Fotios M
FM
D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D007850:Lauric Acids / Q000494:pharmacology; D008566:Membranes / Q000187:drug effects; D051379:Mice; D019814:Myristic Acid / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects*
D003652:Decanoic Acids; D005227:Fatty Acids; D005782:Gels; D007850:Lauric Acids; D019814:Myristic Acid; C030358:lauric acid; C031071:decanoic acid; D000420:Albuterol