Development of lipophilic calcium stearate pellets using ibuprofen as model drug.

INTRODUCTION

The aim of the study was the development of lipophilic pellets containing calcium stearate and ibuprofen as model drug. The pellets were produced by a standard wet extrusion and spheronisation technology. As a main target, the pellets should exhibit sufficient mechanical stability, should not disintegrate in an aqueous vehicle and should show a retarded release kinetic. Furthermore, the drug release should be adjusted only by the ratio between drug and excipient without any additional coating procedure.

METHODS

Different lipids (Precirol(R), Compritol(R), glyceryl monostearate, magnesium stearate and vegetable calcium stearate) were used as lipophilic pelletisation excipients in extrusion/spheronisation using ethanol/water as granulation liquid. The lipids were combined with ibuprofen as a model drug with pH-dependent solubility in several concentrations (15%, 20% and 25% drug content).

RESULTS

Calcium stearate (CS) was found to be a suitable carrier substance for the preparation of spherical pellets (AR1.2). As pellet properties, the mean particle random diameter, surface area, porosity, tensile strength and dissolution profile were determined. By variation of the die plate (1mm, 0.8mm and 0.5mm) and variation of the ethanol/water composition (96% and 50%) of the granulation liquid, pellets in the size range from 800 to 1250microm with a sufficient drug loading capacity up to 20%, a zero-order drug release and high mechanical stability could be produced.

CONCLUSION

The results demonstrated that calcium stearate can be used as pelletisation excipient for slow release formulations by a wet extrusion/spheronisation technique. With this technology, a continuous production of slow release multiple unit preparations will be possible without further coating steps.