Development of a compressed bead-in-capsule drug delivery system for sustained release

Abstract

Multiple-unit pellet systems (MUPS) are solid oral dosage forms consisting of multi-particulates (e.g. coated and/or uncoated beads) compressed into mini-tablets or tablets; or they may be loaded into hard gelatine capsules. Mini-tablet-in-capsule dosage forms are well described in the scientific literature, but no information could be found on mini-MUPS-in-capsule dosage forms. The purpose of this study is to develop a mini-MUPS-in-capsule drug delivery system for sustained drug release. Various bead formulations were prepared by extrusion-spheronisation containing different selected fillers (i.e. Avicel® PH 101, MicroceLac® 100; RetaLac®) and active ingredients (i.e. furosemide and pyridoxine) using a full factorial design. A portion of each formulation of beads was coated using a mixture of the film coating material Eudragit® L 100 and Eudragit® S 100 (50:50) in a rotating pan coater. Uncoated and coated beads were each compressed into mini-MUPS on a Korsch® single tablet press with a 6 mm diameter concave punch. Six mini-MUPS were loaded into a hard gelatine capsule (i.e. three containing coated beads and three containing uncoated beads) to form the mini-MUPS-in-capsule dosage form. Each mini-MUPS-in-capsule drug delivery system was formulated in such a way as to contain 60 mg of active ingredient in total (i.e. 10 mg per mini-MUPS unit). The powder flow properties of the filler materials (i.e. Avicel® PH 101, MicroceLac® 100; RetaLac®) as well as the uncoated and coated beads were evaluated. Scanning electron microscopy (SEM) was used to evaluate the morphology of the powders, uncoated and coated beads as well as the optimum mini-MUPS formulations. The mini-MUPS formulations produced from the factorial design were evaluated in terms of physical properties and dissolution behaviour in order to obtain the optimum formulations for each model compound (furosemide and pyridoxine) and filler (Avicel® PH 101, MicroceLac® 100; RetaLac®) combination investigated in this study. Accelerated stability testing was conducted on the optimised mini-MUPS formulations over a six month period. Neither the physical properties nor the dissolution profiles of the mini-MUPS were improved by film coating of the beads. All mini-MUPS-in-capsule drug delivery systems developed in this study illustrated pulsatile drug release. Therefore, different mini-MUPS-in-capsule drug delivery systems were developed with potential applications for modified drug release in the pharmaceutical industry.