INVITRO RELEASE OF NICOTINIC-ACID ALKYL ESTERS FROM POLOXAMER VEHICLES

Poloxamers are poly(oxyethylene)poly(oxypropylene) block copolymers. Aqueous solutions of these polyols show reverse thermal gelation, low toxicity and good solubilization capacity. As such, they appear to be useful as components of topical drug delivery systems. The objectives of this study were to systematically investigate the effects of (1) poloxamer lipophilicity, (2) poloxamer concentration and (3) temperature on the in vitro release rate of drug from formulations containing hexyl nicotinate. Studies were conducted in a membrane-less model using isopropylmyristate as the receptor phase; for some studies, a series of n-alkyl nicotinates (methyl, ethyl, butyl and hexyl) were used as model compounds. Results indicated that the diffusion coefficients decreased with increasing poloxamer concentration and increased with increasing temperature. Results with different poloxamers indicated that the release rate increased with increasing poloxamer hydrophilic-lipophilic balance (HLB). The order of release rate for alkyl nicotinates was methyl > ethyl > butyl > > hexyl. The markedly lower release rate for hexyl nicotinate was explained by a stronger interaction between drug and poloxamer.