Effect of particle size on in-die and out-of-die compaction behavior of ranitidine hydrochloride polymorphs.

The present study investigates the effect of particle size on compaction behavior of forms I and II of ranitidine hydrochloride. Compaction studies were performed using three particle size ranges [450-600 (A), 300-400 (B), and 150-180 (C) μm] of both the forms, using a fully instrumented rotary tableting machine. Compaction data were analyzed for out-of-die compressibility, tabletability, and compactibility profiles and in-die Heckel and Kawakita analysis. Tabletability of the studied size fractions followed the order; IB > IA > > IIC > IIB > IIA at all the compaction pressures. In both the polymorphs, decrease in particle size improved the tabletability. Form I showed greater tabletability over form II at a given compaction pressure and sized fraction. Compressibility plot and Heckel and Kawakita analysis revealed greater compressibility and deformation behavior of form II over form I at a given compaction pressure and sized fraction. Decrease in particle size increased the compressibility and plastic deformation of both the forms. For a given polymorph, improved tabletability of smaller sized particles was attributed to their increased compressibility. However, IA and IB, despite poor compressibility and deformation, showed increased tabletability over IIA, IIB, and IIC by virtue of their greater compactibility. Microtensile testing also revealed higher nominal fracture strength of form I particles over form II, thus, supporting greater compactibility of form I. Taken as a whole, though particle size exhibited a trend on tabletability of individual forms, better compactibility of form I over form II has an overwhelming impact on tabletability.