DEVELOPMENT OF A FILLER-BINDER DISINTEGRANT FOR DIRECT COMPRESSION TABLETING BY CO-PROCESSING MICROCRYSTALLINE CELLULOSE AND CROSPOVIDONE

ABSTRACT

The aim of the study was to improve the disintegration functionality of microcrystalline cellulose (MCC) as a direct compression excipient in tablet formulation by co- processing MCCwith crospovidone (CPV), a superdisintegrant. Design of Experiment (DoE) approach was adopted to optimize the composition of the co-processed excipient (CPE). The optimized CPE containing MCC (99 %) and CPV (1 %) was prepared using wet massing technique. Solid-state properties of CPE were characterized in comparison to MCC and CPV using optical and scanning electron microscopy (SEM), Powder X- Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infra-red spectroscopy (FT-IR). Powder properties such as flowability, compressibility, moisture sorption capacity, moisture content, dilution potential and lubricant sensitivity ratio (LSR) were also evaluated using standard techniques. Compaction studies were carried out using Heckel and Kawakita equations as well as compressibility-tabletability-compactibility (CTC) profiling. Tablets were formulated by direct compression incorporating metronidazole as the model drug and properties of tablets evaluated.

The study revealed an increase in particle size which enhanced the flowability of MCC as a co-processed excipient. Solid state properties of CPE revealed a material consisting of irregular shaped fibrous particles characterized by a rough texture. PXRD and DSC scans presented a material that is semi-crystalline in nature. Moisture content and moisture sorption capacity of MCC was found to decrease as a result of co-processing. The extent of plastic deformation was reduced in MCC when co-processed with CPV and this translated to a reduction in the tabletability of MCC. Tablets formulated with CPE disintegrated at 11.48mins as compared to MCC tablets that disintegrated at 26.88 mins and this was reflected in the in vitro drug release profile with CPE tablets

attaining maximum drug release at 20mins compared to MCC tablets that attained maximum drug release at 60mins. Thus, the functionality of MCC as a disintegrating filler binder for direct compression tableting was improved by co-processing with crospovidone.