Context: A nonoral alternative such as transdermal system is desired to improve bioavailability and to maintain a constant and prolonged drug level with reduced frequency of dosing.
Objective: The objective of the investigation is to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the influence of chemical permeation enhancers (CPEs) on the percutaneous permeation pattern.
Material And Methods: A D-optimal mixture design was used to study the influence of CPE with oleic acid (OA), lauric acid, and propylene glycol (PG) as mixture components. The influence of chemical enhancers on skin permeation was compared using one-way analysis of variance followed by multiple comparison analysis. Criterion of desirability was used to optimize the therapeutic system. Preclinical studies in rabbits were also carried out to establish an ex vivo-in vivo correlation (EVIVC).
Results: The drug permeation pattern suggested Higuchian diffusion as predominant mode followed by case II to super case II transport as drug transport mechanism. The optimized formulation was obtained using 5% (w/w) CPE consisting of a blend of 62.41% OA and 37.59% PG. About twofold increase in alfuzosin permeation was achieved with the optimized transdermal patch. An approximate linear EVIVC was established (R(2) = 0.971).
Discussion: The optimized blend of enhancers could improve skin permeation parameters. A higher extent of in vivo skin permeation compared with cadaver skin permeation may be due to more permeable nature of rabbit skin.
Conclusion: The investigations suggest an effective alternative delivery strategy such as transdermal systems for alfuzosin hydrochloride.
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| http://dx.doi.org/10.3109/03639045.2010.522192 | DOI Listing |
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