In vitro evaluation of a pH-sensitive hydrogel for control of GI drug delivery from silicone-based matrices

Abstract

The release of drugs having very different aqueous solubilities and partitioning properties, such as salicylamide (SAM), nicotinamide (NAM), clonidine·HCl (CHC) and prednisolone (PDN), from 1 mm thick silicone discs containing, in dispersion, around 35 wt% medicated granules of a pH-sensitive hydrogel, is studied in vitro. The hydrogel is a poly(acrylic acid) (PAA):poly(ethylene oxide) interpenetrating polymer network (IPN). The matrices are eluted with simulated GI fluids, i.e., with a medium of pH 1.2 for 2 h, followed by a medium of pH 6.8 for 2 h, followed by a medium of pH 7.4 for 5 h. The release rate pattern is always bimodal and is determined by the pH-dependent swelling of the IPN granules in matrix. In simulated gastric fluid (SGF) the IPN swelling degree is low and the release is limited to an initial burst, followed by a rapid decline. In simulated intestinal fluid (SIF), PAA in the IPN becomes ionized, the IPN swelling degree increases and the release rate rises to a second maximum. The drug fraction released is always preponderant in SIF compared to SGF. The matrix swelling and drug release rates are influenced by the granule size. With a loading dose of 5 wt% in IPN granules in the 355–425 μm size range, SAM, NAM and PDN show the same release rates in SIF. Differences arise when the load is raised to 20 wt% and/or the granule size range is reduced to 105–250 μm. CHC shows an ionic interaction with PAA in the IPN, which limits the release rate in SIF. The release of drugs not ionically interacting with PAA is virtually uninfluenced by ample variations in osmolality, ionic strength and buffer molarity of dissolution medium.