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 holders immersed in 250 mL of simulated tear fluid and detecting the ultraviolet absorbance on-line. Gels were characterized by using a controlled rate rheometer, and surfactant aggregates were characterized by using cryo-transmission electron microscopy.
RESULTS: The diffusion coefficient of alprenolol was 2.8 x 10(-6) cm2/s in a lipophilically modified poly(acrylic acid) gel without surfactants present and 0.14 x 10(-6) cm2/s when formulated with 1% sodium dodecyl sulfate. For fluvastatin, the diffusion coefficient changed from 3.0 x 10(-6) cm2/s to 0.07 x 10(-6) cm2/s in the presence of 0.2% benzyldimethyldodecyl-ammonium bromide. Alprenolol, betaxolol, metoprolol, diphenhydramine, and fluvastatin formed vesicles with oppositely charged surfactants in physiologic salt conditions.
CONCLUSIONS: In this article we show that it is feasible to control the release of charged drugs from gels by using surfactants. Vesicles are generally formed when surface active drugs are mixed with oppositely charged surfactants 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 also give a slower release.