Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-Ku, Okayama, 700-8530, Japan.
Formulation R&D Laboratory, Research Division, Shionogi & Co., Ltd., 2-1-3 Kuise Terajima, Amagasaki, Hyogo, 660-0813, Japan.
Pharm Res. 2023 Dec;40(12):3073-3086. doi: 10.1007/s11095-023-03630-w. Epub 2023 Nov 14.
Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system.
Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs.
To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen.
This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments.
交联羧甲纤维素钠通常用作药物制剂中的超级崩解剂，在碱性 pH 条件下会水解形成凝胶结构。利用交联羧甲纤维素钠的这一特性，我们开发了一种新型的缓释（SR）系统。
制备含有交联羧甲纤维素钠、碱性赋形剂和/或羟丙甲纤维素（HPMC）的速释（IR）和 SR 片剂，并考察其湿强度和体外药物释放行为。在禁食的比格犬中评估 IR 片剂、HPMC 片剂和我们新型 SR 片剂的体内口服药物吸收情况。
为了在生理条件下形成凝胶结构，在含有交联羧甲纤维素钠的配方中加入碱性赋形剂。此外，使用 HPMC 使凝胶结构具有足够的抗机械破坏的强度。由交联羧甲纤维素钠、碱性赋形剂和 HPMC 组成的新型碱化交联羧甲纤维素钠-HPMC（ACSH）SR 片剂成功地实现了对醋氨酚、布洛芬或盐酸尼卡地平的缓释。与 IR 片剂相比，在使用小体积液体进行的释放研究中，ACSH SR 系统提供了更好的醋氨酚释放效果，而不含交联羧甲纤维素钠的 HPMC 片剂则没有。体内口服吸收研究表明，ACSH SR 系统成功地抑制并延长了醋氨酚的血浆浓度。
这种由交联羧甲纤维素钠、碱性赋形剂和 HPMC 制备的新型 ACSH SR 系统有望成为一种有前途的 SR 制剂，可使药物在远端肠道段实现大量吸收。
