Matrix mini-tablets based on starch/microcrystalline wax mixtures

Abstract

Matrix mini-tablets based on a combination of microcrystalline waxes and starch derivatives were prepared using ibuprofen as a model drug. The production of mini-tablets was preferred over the production of pellets, as up-scaling of the pelletisation process seemed problematic. Prior to tabletting, melt granulation in a hot stage screw extruder and milling were required. The in vitro drug release was varied using microcrystalline waxes with a different melting range, the slowest drug release being obtained with a formulation containing a microcrystalline wax with a melting range between 68 and 72°C. Generally speaking increasing the wax concentration resulted in a slower drug release. In vitro drug release profiles were also modified using different starches and mixtures of starches. Increasing the ibuprofen concentration to 70% resulted in a faster drug release rate.

Introduction

Mini-tablets (micro tablets) are tablets with a diameter equal to or smaller than 2–3 mm (Lennartz and Mielck, 1998). These mini-tablets can be filled into hard gelatin capsules for the production of a sustained release multiple unit dosage form which has definite advantages over single unit dosage forms. These advantages are: less risk of dose dumping, less inter- and intra- subject variability, high degree of dispersion in the digestive tract thus minimizing the risks of high local drug concentrations (Bechgaard and Nielsen, 1978, Follonier and Doelker, 1992). Mini-tablets also offer an alternative for pellets because of their relative ease of manufacturing and because dosage forms of equal dimensions and weight with smooth regular surface are produced in a reproducible and continuous way. Mini-tablets are very suitable for coating in order to sustain the drug release but the coating process is expensive, time consuming and sometimes associated with reproducibility problems of release during storage. So the development of mini-matrices to control the drug release has gained a lot of interest. Several papers have already been published describing matrix mini-tablets based on hydrophilic (Colombo et al., 1985, Feely and Davis, 1989, Bongiovanni et al., 1992, Østberg et al., 1994, Clancy and Cumming, 1998, Rouge et al., 1997, Rouge et al., 1998, Sujja-areevath et al., 1998) as well as hydrophobic materials (Önay-Başaran and Olsen, 1985, Önay-Başaran et al., 1985, Ratsimbazafy et al., 1996). The aim of the present work was the preparation of matrix mini-tablets based on a combination of microcrystalline wax and a starch derivative in order to sustain the drug release. Formulations based on these components have already been described (Zhou et al., 1996) as flexible matrix systems when producing pellets by a melt pelletisation process, but up-scaling of this production process proved problematic.