The effect of wet granulation on the erosion behaviour of an HPMC-lactose tablet, used as a rate-controlling component in a pulsatile drug delivery capsule formulation

Jason T McConville, A. Ross, A.R. Chambers, G. Smith, A.J. Florence, H. Stevens

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The purpose of this study was to investigate the variability in the performance of a pulsatile capsule delivery system induced by wet granulation of an erodible HPMC tablet, used to seal the contents within an insoluble capsule body. Erodible tablets containing HPMC and lactose were prepared by direct compression (DC) and wet granulation (WG) techniques and used to seal the model drug propranolol inside an insoluble capsule body. Dissolution testing of capsules was performed. Physical characterisation of the tablets and powder blends used to form the tablets was undertaken using a range of experimental techniques. The wet granulations were also examined using the novel technique of microwave dielectric analysis (MDA). WG tablets eroded slower and produced longer lag-times than those prepared by DC, the greatest difference was observed with low concentrations of HPMC. No anomalous physical characteristics were detected with either the tablets or powder blends. MDA indicated water-dipole relaxation times of 2.9, 5.4 and 7.7×10−8 ms for 15, 24 and 30% HPMC concentrations, respectively, confirming that less free water was available for chain disentanglement at high concentrations. In conclusion, at low HPMC concentrations water mobility is at its greatest during the granulation process, such formulations are therefore more sensitive to processing techniques. Microwave dielectric analysis can be used to predict the degree of polymer spreading in an aqueous system, by determination of the water-dipole relaxation time.

Original languageEnglish
Pages (from-to)541-549
Number of pages8
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number3
Early online date11 Mar 2004
Publication statusPublished - 2004


  • microwave dielectric analysis
  • high shear granulation
  • erosion
  • HPMC
  • pulsatile delivery
  • lag-time

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