Differential compaction behaviour of roller compacted granules of clopidogrel bisulphate polymorphs

Abstract

In the present work, in-die and out-of-die compaction behaviour of dry-granulated powders of clopidogrel bisulphate (CLP) polymorphs, form I and form II, was investigated using a fully instrumented rotary tablet press. Each polymorph was compacted at three different roller pressures [70.3 (S1), 105.5 (S2) and 140.6 (S3)kgf/cm2], and obtained granules were characterized for their physico-mechanical properties. Compaction data were analyzed for out-of-die compressibility, tabletability and compactibility profiles, and in-die Heckel, Kawakita and Walker analysis. The roller compacted granules of both forms showed markedly different tabletting behaviour. Roller pressure exhibited a trend on compaction behaviour of form I granules, whereas, in case of form II, the effect was insignificant. Tabletability of the six granule batches follows the order; I_S1>I_S2>I_S3>II_S1≈II_S2≈II_S3. In case of form I, the reduced tabletability of the granules compacted at higher roller pressure was attributed to the decreased compressibility and plastic deformation. This was confirmed by compressibility plot and various mathematical parameters derived from Heckel (Py), Kawakita (1/b) and Walker (W) equations. The reduced tabletability of form I granules was due to ‘granule hardening’ during roller compaction. On the other hand, insignificant effect of roller compaction on tabletting behaviour of form II granules was attributed to brittle fragmentation. The extensive fragmentation of granules offered new ‘clean’ surfaces and higher contact points that negated the effect of granule hardening.