Evaluation of a pH-sensitive semi-interpenetrating polymer network for control of GI drug delivery

Abstract

The ability of a pH-sensitive semi-interpenetrating polymer network (semi-IPN), composed of crosslinked polyethylene glycol 8000 (P8000C) and Eudragit L100 (EUD), to control the release of drugs having very different aqueous solubilities, such as nicotinamide (NAM) and salicylamide (SAM), from silicone-based matrices to simulated GI fluids, is evaluated in vitro. P8000C and EUD form an interpolymer complex through hydrogen bonding. The semi-IPN equilibrium swelling in simulated gastric fluid (SGF) depends inversely on the EUD fraction in the complex. In simulated intestinal fluid (SIF) the P8000C-EUD complex dissociates, EUD dissolves and diffuses out of the P8000C network and the swelling markedly increases. Drug release from 1-mm thick silicone disk matrices containing, in dispersion, around 35 wt% medicated semi-IPN granules is studied by eluting matrices with SGF for 2 h, followed by SIF for 7 h. Increasing EUD fractions in semi-IPN decrease the release rate in SGF and tend to linearize the overall release profile. Pseudo-zero order release, for either NAM or SAM, is obtained with semi-IPN granules composed of P8000C/EUD 1:2. The fractional release rate shows limited dependence on the dose, in the 5–20% range of drug loads in granules, and on the drug type. Dose fractions in between 50% and 80% are released in 9 h. Drug release is virtually uninfluenced by ample variations in osmolality, ionic strength and buffer molarity of dissolution medium.