Effectiveness of binders in wet granulation: a comparison using model formulations of different tabletability.

Abstract Based on an analysis of model granulates and tablets, a comparison was made of the effectiveness of the binders PVP K30 PH, Cellulose HP-M 603, Lycatab DSH, Lycatab PGS, and L-HPC (type LH 11). A high shear mixer was used to prepare two model granulates (placebo and paracetamol) under processing conditions which were, as far as possible, comparable. The binders were added as proportions of 2%, 6%, and 10%. Water was used as the granulating liquid. The properties of the placebo granulates (particle size distribution, bulk and tapped density, granule strength, flow properties), and those of the tablets (crushing strength, friability) prepared from these granulates under different compaction forces, were generally good. However, with PVP, Cellulose HP-M603, and Lycatab, the disintegration time of the tablets did not meet pharmacopoeial requirements even though a "disintegrant" was used in the "outer phase." The paracetamol formulations were prime examples of high-dose drug substances with particularly poor granulating and tabletting properties, well suited to reveal differences between the binders. The paracetamol granulates were of higher friability and less flowability than the placebo granulates. The tablets tended to cap, friability was (with few exceptions) high, and disintegration times were long. In the preparation of model tablets containing paracetamol, PVP K30 PH (6%). and Cellulose HP-M 603 (6%) turn out to be the binders of choice with respect to crushing strength, but the disintegration times are too long. Lycatab PGS, Lycatab DSH, and L-HPC-LH 11 could not be used to produce paracetamol tablets that met the requirements.