DEVELOPMENT OF RECTALLY ADMINISTERED PROLONGED-RELEASE HARD GELATIN CAPSULES USING DIFFERENT POLYMERS AS DILUENTS

The hard gelatin capsule has recently been shown to provide an alterna tive dosage form for rectal drug administration. However, it is obviou s that the pharmaceutical additives used in the capsule have a marked effect on the biopharmaceutical characteristics of the product. The ai m of this study was to investigate whether it is possible to develop p rolonged-release hard gelatin capsules for rectal administration using hydrophilic polymers, hydroxypropylmethyl cellulose and polycarbophil as diluents in the capsule. An ibuprofen capsule containing only lact ose as a diluent was used as the only diluent, adequate prolonged-rele ase rectal capsules could be prepared with a low viscosity-grade (100 mPa) of hydroxypropylmethyl cellulose. As compared to the lactose-base d capsule, the t(max) and increased and the C-max decreased, but there was no change in the AUC value. With a higher viscosity-grade (4000 m Pa) of hydroxypropylmethyl cellulose, the extent of bioadvailability b egan to decline. Polycarbophil as the only diluent totally blocked the absorption of the model drug. When the diluent consisted of 5% polyca rbophil and 95% lactose, an appropriate prolonged-release ibuprofen ca psule was once again obtained. Classic pharmacopoeial dissolution test s poorly predicted the in vivo behaviour of the capsules in man. The p resent study also confirmed that training in the administration techni que and use of a glidant are of great importance for adequate dosing o f hard gelatin capsules via the rectal route.