Effect of polyunsaturated fatty acids and some conventional penetration enhancers on transdermal delivery of atenolol.
The aim of our present study was to evaluate the in vitro percutaneous absorption of atenolol, a well-known antihypertensive, from a series of formulations containing various penetration enhancers. Particularly the promoting effect of EPA and DHA, two polyunsaturated fatty acids (PUFAs), has been studied, and drug permeation data have been compared with those obtained with the other formulations containing "classic" penetration enhancers such as transcutol, d-limonene, and PG. Not all the penetration enhancers tested were effective in increasing atenolol percutaneous flux and the best permeation profile for atenolol was obtained with the formulation containing transcutol (B) and PUFA (E). To explain the enhancer mechanism, the atenolol diffusion and partitioning coefficients from the different formulations were calculated. The results indicated that PUFAs increased the apparent diffusion coefficient of the drugs but did not affect their apparent stratum corneum (SC)/vehicle partition coefficient (K(m)). At this same time transcutol exerted its enhancer effect increasing significantly the apparent SC/vehicle partition coefficient (K(m)) and in a minor amount the apparent diffusion coefficient of skin permeation process (D(m)). The potential application of formulations B and E in atenolol percutaneous absorption was determined from the calculation of the steady-state plasma concentrations (C(ss)). These values resulted within the drug therapeutic range and suggest that atenolol transdermal delivery could be feasible.
Puglia
Carmelo
C
Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, Catania, Italy. capuglia@unict.it
Bonina
Francesco
F
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D001262:Atenolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D012869:Skin Absorption / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet
D000319:Adrenergic beta-Antagonists; D005079:Excipients; D005231:Fatty Acids, Unsaturated; D001262:Atenolol