The effect of formulation composition and dissolution parameters on the gel strength of controlled release hydrogel tablets.

The impact of hydrogel polymers and dissolution media on tablet gel strength, Gamma, 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. Gamma 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. Gamma, however, showed large and significant differences (p < or = 0.05) between tablets containing different polymers and between different dissolution media. Gamma values were HPMC KI00MP > HPC HXF > carbomer 971P (same % w/w) with absolute Gamma values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Gamma for HPMC based tablets was independent of changes in dissolution media, while the Gamma 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 Gamma values in all dissolution media and an unexpected 58% lower Gamma in buffer compared with DI water or acid. Gamma 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.