Correlating cellulose derivative intrinsic viscosity with mechanical susceptibility of swollen hydrophilic matrix tablets

Abstract

Hydrophilic matrix tablets are prone to mechanical stress while passing through the gastrointestinal tract, which may result in inappropriate drug-release characteristics. Intrinsic viscosity is a physical polymer property that can be directly compared across various types and grades of polymers and correlated with the mechanical susceptibility of swollen matrix tablets. Five tablet formulations containing different HPMC and HPC polymers were prepared and analyzed using an in vitro glass bead manipulation test. The dissolution rate results were modeled using the Korsmeyer-Peppas equation and a correlation was found between the fit constants k and n, goodness-of-fit measure parameters, and intrinsic viscosity. Moreover, the dissolution profiles were used to calculate the degree of mechanical susceptibility for each formulation, defined as the ratio of the average dissolution rate after manipulation and the initial dissolution rate before manipulation. It was confirmed that an increased intrinsic viscosity polymer value resulted in a decrease in mechanical susceptibility. Considering this, two simple rules were defined for designing robust matrix tablets with respect to mechanical stresses.

Fig. 1

Mean dissolution profiles for tablet formulations tested (compositions from F1 to F5 are presented in Table I) under mechanical stress test conditions in water as a dissolution medium: a 20 h time scale with SD error bars (n = 3), b 3 h time scale, manipulation at 1.5 h is indicated

Fig. 2

Mechanical stress simulation test: percent of dissolved drug versus time (h) for tablet formulations studied (compositions from F1 to F5 are presented in Table I) using water as a dissolution medium. Dashed lines represent curves after fitting the dissolution profiles to Eq. 2: a 20 h time scale, b same plot up to 10 h

Fig. 3

Relationship of Korsmeyer–Peppas fit constants (k and n) and goodness-of-fit measures (and ) with respect to the polymer intrinsic viscosity. Open points were not included in the linear trend but are plotted on the same figure to show the effect of increased polymer concentration (F3 versus F2)

Fig. 4

Percent of released drug versus time for Formulation F4 tested with mechanical manipulation (straight line) and without manipulation (dashed line). Note that the linear assumption of release until 1.5 h is justified by the dissolution result at 1 h of sampling time point

Fig. 5

The degree of mechanical susceptibility (MS), after mechanical stress application for formulations tested. Ratios greater than 1 indicated that tablets were mechanically susceptible

Fig. 6

Mechanical susceptibility (MS) immediately after mechanical stress application for tested formulations F1 to F5 as a function of polymer intrinsic viscosity

Fig. 7

Comparison of mechanical susceptibility (MS) immediately after mechanical stress application for tested formulations F2 and F3 with various amounts of HPMC K4M polymer