Song Seh Hyon, Chae Bo Ram, Sohn Se Il, Yeom Dong Woo, Son Ho Yong, Kim Jin Han, Kim Sung Rae, Lee Sang Gon, Choi Young Wook
Daewon Pharm. Co., Ltd., 520 Cheonhodae-ro, Gwangjin-gu, Seoul 04994, Republic of Korea.
College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
Int J Pharm. 2016 Sep 25;511(2):864-75. doi: 10.1016/j.ijpharm.2016.07.074. Epub 2016 Aug 1.
To develop a matrix-type, controlled-release tablet formulation of pelubiprofen (PLB), a recently developed non-steroidal anti-inflammatory drug, polymeric excipients including hypromellose, hydroxypropylcellulose, Eudragit(®) RS PO, and Kollidon(®) SR were screened. A formulation containing 12.4% w/w Kollidon(®) SR (K2 tablet) was found to be the most promising and stable for 6 months in an accelerated stability test. PLB release from K2 tablet was limited at pH 1.2, but gradually increased at pH 6.8 with a surface-erosion, resulting in the best fit to Hixson-Crowell equation. Comparative human PK studies were performed using a randomized, 2-way crossover design. LC-MS/MS assay revealed that the plasma level of PLB-transOH, an active metabolite, was significantly higher than that of PLB. After multiple dosing of immediate-release tablet (R) and K2 tablet (T), the T/R ratios of AUC were 1.02 and 1.04 for PLB and PLB-transOH, respectively. Level A in vitro-in vivo correlation was established for the K2 tablet-administered group. PK profile of PLB-transOH was not influenced by food intake, while that of PLB was altered. We suggest that K2 tablet could be administered twice a day without being affected by food intake, thereby enhancing patient compliance.
