The influence of polymorphism on the manufacturability and in vitro dissolution of sulindac-containing hard gelatin capsules

Context: Drug polymorphism could affect drug product dissolution, manufacturability, stability and bioavailability/bioequivalence. The impact of polymorphism on the manufacturability and in vitro dissolution profiles of sulindac capsules has not been studied yet. Objective: To evaluate the impact of polymorphism on the manufacturability and in vitro dissolution of sulindac hard gelatin capsules. Materials and methods: Sulindac crystal forms I and II (SLDI and SLDII, respectively) were prepared and characterized. Powder formulations containing one of the polymorphs, lactose and magnesium stearate (at three different levels) were prepared and their flow properties determined. Hard gelatin capsules were filled with the formulations and tested for fill-weight variations. Drug dissolution for SLDI- and SLDII-containing hard gelatin capsules was determined. Results: Differences in flow properties for each polymorph were observed, as well as for their formulations, which in turn affected capsule weight homogeneity. Statistically significant differences in the rate and extent of drug release were observed between SLDI- and SLDII-containing capsules. Discussion: Formulations containing SLDI showed a better manufacturability and a better dissolution profile than those with SLDII. Conclusion: Sulindac crystalline form I was the best candidate for hard gelatin capsule formulation because of its technological and in vitro dissolution properties.