Salt effects on the diffusion and release rate of propranolol from poloxamer 407 gels

In this report we show that salts commonly included in the formulation of poloxamer 407 (P407) gels can dramatically change the release rate of a drug from the gel. We used a model drug, propranolol, and measured its diffusion from a 21% P407 gel into an aqueous medium at 37 degrees C through a cellulose membrane. The data followed the Higuchi square root law during the first hour of release. The release rate and diffusion coefficient of propranolol were significantly reduced when NaCl, Na2SO4, NaH2PO4, MgSO4 and CaCl2, were added to the gels. The magnitude of the effect on release rate depends on the nature and concentration of the salt. Since propranolol is expected to be located outside the micelles in the gel, we attribute these salt effects to an increase in microviscosity of the aqueous regions of the gel, rather than to a change in micellization behavior. This is analogous to the change in the aggregation and phase behavior of aqueous solutions of non-ionic surfactants in the presence of salts. (C) 1998 Elsevier Science B.V. All rights reserved.