The Effect of Formulation Composition and Dissolution Parameters on the Gel Strength of Controlled Release Hydrogel Tablets

Abstract

The impact of hydrogel polymers and dissolution media on tablet gel strength, Γ, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo® lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Γ was measured using a previously reported method. The drug dissolution profiles were similar, irrespective of polymer type or dissolution media (DI water, 0.1 N HCl, and pH 6.8 phosphate buffer), at the same % w/w level of polymer. Γ, however, showed large and significant differences (p≤0.05) between tablets containing different polymers and between different dissolution media. Γ values were HPMC K100MP > HPC HXF > carbomer 971P (same % w/w) with absolute Γ values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Γ for HPMC based tablets was independent of changes in dissolution media, while the Γ values for HPC tablets were 18% lower in acid and buffer than in DI water. Of the polymers tested, carbomer based tablets had the lowest Γ values in all dissolution media and an unexpected 58% lower Γ in buffer compared with DI water or acid. Γ provides a quantitative measure of the effect of formulation and dissolution parameter changes on tablet gel layer strength, under in vitro stress conditions that may parallel in vivo tablet performance, but which cannot be deduced from a comparison of dissolution profiles or polymer viscosity.