Drug release from pH-response polyvinylacetal diethylaminoacetate hydrogel, and application to nasal delivery

Nasal formulations of polyvinylacetal diethylaminoacetate (AEA) were prepared and the effect of AEA concentration on drug release was evaluated in in vitro and in vivo experiments. The profiles of release of drug from dialysis tubes had both a rapid and a slow phase, and had an inflection point, at which AEA hydrogel formation appeared to occur. The higher the AEA concentration, the lower the rate of drug release observed. The apparent disappearance rate constant (k(app)) of drug was determined by the deposit method, which estimates changes in the amount of residual drug in the nasal cavity with the lavage technique following administration. Drug k(app) values decreased with increase in AEA concentration. Hydrogel formation on mucous membranes was also visually confirmed in rat nasal cavity. AEA preparations which facilitate instillation into the nose but which form hydrogel on the mucous membrane are potentially useful for controlled-release nasal delivery systems. (C) 1998 Elsevier Science B.V. All rights reserved.