用于结肠给药的美沙拉秦 400 毫克缓释片的设计、优化和体外评估

Diponkor Kumar Shill, U. Kumar, Asm Monjur Al Hossain, Dilshad Noor Lira, A. S. Rouf
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摘要

溃疡性结肠炎是一种慢性炎症性疾病,如果直接在结肠中给药,患者将获得更多益处。美沙拉嗪可直接进入结肠治疗溃疡性结肠炎。在此,我们旨在采用质量源于设计(QbD)的方法,设计并优化美沙拉秦 400 毫克缓释片,用于结肠特异性给药。首先将片剂配制成优化的核心片剂,然后用 Eudragit S 12.5 包衣,以确保结肠给药。核心片剂的实验设计采用 32 全因子设计,其中淀粉乙醇酸钠(SSG)和聚乙烯吡咯烷酮(PVP K-30)的百分比为自变量,片剂硬度(kg/cm2)和 1.5 小时后在 pH 值为 7.2 的磷酸盐缓冲液中的累积药物释放百分比为响应变量。通过对初步探索配方的反应进行评估,开发出一种优化配方,使其硬度值达到 7-8 公斤/平方厘米,并在 pH 值为 7.2 的缓冲液中达到最大的药物释放量。优化配方中使用了 SSG 和 PVP K-30,含量分别为 3.05% 和 1.69%。优化芯片的硬度和累积药物释放率分别为 7.8 kg/cm2 和 91.76%。利用 XRD、FTIR 和 TGA 研究了药物与辅料的相容性。然后用 Eudragit S 12.5 包衣优化后的核心片剂,以将药物选择性地输送到结肠,并进一步评估其体外溶出度。溶出度研究表明,增重 7.4% 的包衣片剂具有最大的累积药物释放率(91.19 ± 0.11%),药物释放曲线为零阶(R2 = 0.943)。根据 ICH Q1A (R2) 指南,在加速储存条件下进行了稳定性研究,结果表明药物含量在储存期间没有显著变化,这表明配制的片剂批次具有稳定性。这些数据共同表明,通过 QbD 方法开发的美沙拉嗪片剂具有优异的物理性质和药物释放特性,因此可推荐用于商业生产。Dhaka Univ.22(2):189-201,2023 年(12 月)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design, Optimization and In vitro Evaluation of Mesalazine 400 mg Delayed Release Tablet for Colon Specific Delivery
Ulcerative colitis is a chronic inflammatory disease, and patients would get benefit more if the drug is given directly to the colon. Mesalazine is intended to deliver to the colon for treating ulcerative colitis. Here, we aimed to design and optimize mesalazine 400 mg delayed release tablet for colon-specific delivery using a quality by design (QbD) approach. The tablet was first formulated as an optimized core tablet and then coated with Eudragit S 12.5 for ensuring colonic delivery. The experimental design for the core tablet was constructed using a 32 full factorial design, where the percentages of sodium starch glycolate (SSG) and polyvinylpyrrolidone (PVP K-30) were independent variables and the tablet hardness (kg/cm2) and cumulative percentage of drug release at pH 7.2 phosphate buffer after 1.5 hours were treated as responses. Responses obtained from the initial exploratory formulations were evaluated to develop an optimized formulation to have a hardness value of 7-8 kg/cm2 and the maximum amount of drug release at pH 7.2 buffer. The optimized formulation involved the use of SSG and PVP K-30 at 3.05% and 1.69%, respectively. Hardness and cumulative percent of drug release obtained for the optimized core tablet were 7.8 kg/cm2 and 91.76%, respectively. The compatibility of drug and excipients was studied utilizing XRD, FTIR and TGA. The optimized core tablet was then coated with Eudragit S 12.5 to deliver the drug selectively to the colon and further assessed for its in vitro dissolution. Dissolution studies indicated that coated tablets with a weight gain of 7.4% exhibited the maximum cumulative percent of drug release (91.19 ± 0.11%), with a zero-order drug release profile (R2 = 0.943). A stability study performed according to ICH Q1A (R2) guidelines at accelerated storage conditions identified that there was no significant change in drug content over the storage period, indicating the stability of the formulated tablet batches. Together, these data suggest that the mesalazine tablet developed through the QbD approach offers excellent physical properties and drug release profile and, therefore, could be recommended for commercial manufacturing. Dhaka Univ. J. Pharm. Sci. 22(2): 189-201, 2023 (December)
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