Bioavailability and in vitro oesophageal sticking tendency of hydroxypropyl methylcellulose capsule formulations and corresponding gelatine capsule formulations

Abstract

The overall aim of the present study was to widen our knowledge about the biopharmaceutical behaviour of novel hydroxypropyl methylcellulose (HPMC)-based two-piece capsules by comparing them with the classic hard gelatine capsules. Firstly, the tendency of the HPMC capsules to stick to isolated porcine oesophageal preparation was evaluated. The force needed to detach the HPMC capsules from the oesophagus was significantly lower than that for the gelatine capsules ( P<0.001), which is evidently an advantage of this new dosage form. The second aim was to investigate the possibility of preparing sustained-release capsules using different powdered HPMCs as diluents (K100, K4M and K15M) and the effect of the molecular weight of HPMC powder on the in vitro and in vivo behaviour of the capsules. In addition to peroral drug administration also rectal dosing was applied. Two groups of eight healthy volunteers participated in randomised, cross-over, single-dose studies. One group was administered capsules orally and the other rectally. There were no marked differences in the bioavailability properties of either the oral or rectal HPMC capsules containing ibuprofen as model drug as compared with corresponding gelatine capsule formulations. Using different viscosity grades of HPMC powders as diluents it was possible to control the absorption rate of the model drug both from gelatine and HPMC capsules as far as the oral route was concerned. After rectal administration there were no statistically significant differences between the formulations containing different grades of HPMC powder. Only partial correlation was observed between the results of the bioavailability studies and the in vitro dissolution studies. From a biopharmaceutical point of view these two shell materials can be regarded as interchangeable.