Controlled drug release from gels using surfactant aggregates. II. Vesicles formed from mixtures of amphiphilic drugs and oppositely charged surfactants

Purpose. The aim of this study was to control the release of charged drugs from gels by adding surfactants that can interact with the drug and polymer matrix. Methods. The in vitro release from gels was measured by using 6-mL gel hold ers immersed in 250 mL of simulated tear fluid and detecting the ultraviole t absorbance on-line. Gels were characterized by using a controlled rate rh eometer, and surfactant aggregates were characterized by using cryo-trans m ission electron microscopy. Results. The diffusion coefficient of alprenolol was 2.8 . 10(-6) cm(2)/s i n a lipophilically modified poly(acrylic acid) gel without surfactants pres ent and 0.14 . 10(-6) cm(2)/s when formulated with 1% sodium dodecyl sulfat e. For fluvastatin, the diffusion coefficient changed from 3.0 . 10(-6) cm( 2)/s to 0.07 . 10(-6) cm(2)/s in the presence of 0.2% benzyldimethyldodecyl -ammonium bromide. Alprenolol, betaxolol, metoprolol, diphenhydramine, and fluvastatin formed vesicles with oppositely charged surfactants in physiolo gic salt conditions. Conclusions. In this article we show that it is feasible to control the rel ease of charged drugs from gels by using surfactants. Vesicles are generall y formed when surface active drugs are mixed with oppositely charged surfac tants in physiologic conditions. The strongest effects on the release rate are seen for lipophilically modified polymer gels in which the drug and the oppositely charged surfactant form vesicles, but systems with micelles als o give a slower release.