RESUMO
The purpose of this study was to develop an extended-release (ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS) and hydroxypropylcellulose (HPC) were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.
RESUMO
The purpose of this study was to develop a new method using beagle dogs in order to evaluate the colonic absorption properties of oral extended-release (ER) solid dosage forms. The established method is not only noninvasive and inexpensive but full-sized ER dosage forms are also directly administered to the colons of conscious dogs through the anus with an endoscope and modified bioptome. In the method, it was possible to administer the ER dosage forms into the ascending colon of dogs within 30 s-1 min. The colonic absorption of Voltaren-XR (Diclofenac sodium), Glucophage-XR (metformin), Pacif (morphine hydrochloride), Herbesser-R (diltiazem hydrochloride) and Plendil (felodipine), which are currently on the market, were investigated by this method. The relative bioavailabilities of these ER dosage forms to oral drug solution were 100.3%, 42.5%, 60.6%, 46.3% and 29.8%, respectively. Some of these results reflected the human colonic absorption profiles reported in the literature. This newly developed method could provide researchers with an alternative way to predict the human colon absorption performance of oral ER delivery systems.
