Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

• Published in: Asian journal of pharmceutical sciences Vol. 12; no. 2; pp. 149 - 156
• Main Authors: Fukui, Sachiko, Yano, Hideki, Yada, Shuichi, Mikkaichi, Tsuyoshi, Minami, Hidemi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2017; Shenyang Pharmaceutical University; Elsevier
• Subjects: Extended-release matrix tablet; Hydroxypropylcellulose; Hypromellose acetate succinate; Original; Robust dissolution; USP apparatus 3; Hypromellose acetate succinate; USP apparatus 3; Robust dissolution; Extended-release matrix tablet; Hydroxypropylcellulose
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2016.11.002

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.