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.
['Guadalupe Sánchez-González|Elizabeth|E|', 'Yépez-Mulia|Lilian|L|', 'Jesús Hernández-Abad|Vicente|V|', 'Jung Cook|Helgi|H|']
D000894:Anti-Inflammatory Agents, Non-Steroidal D002214:Capsules D002626:Chemistry, Pharmaceutical D003460:Crystallization D065546:Drug Liberation D005079:Excipients D005780:Gelatin D007785:Lactose D011208:Powders D012995:Solubility D013229:Stearic Acids D013467:Sulindac
polymorphs manufacturability Formulation mechanical properties physical characterization