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采用直接压片技术制备的新型琥珀酸索利那新生物等效片剂,以提高化学稳定性。

Novel Bioequivalent Tablet of Solifenacin Succinate Prepared Using Direct Compression Technique for Improved Chemical Stability.

作者信息

Kim Do Hwan, Ho Myoung Jin, Jeong Chan Kyu, Kang Myung Joo

机构信息

College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si 31116, Chungcheongnam-do, Republic of Korea.

Shin Poong Pharm. Co., Ltd., 1203-ho Daerung Techno Town 15, 401, Simin-daero, Dongan-gu, Anyang-si 14057, Gyeonggi-do, Republic of Korea.

出版信息

Pharmaceutics. 2023 Jun 14;15(6):1723. doi: 10.3390/pharmaceutics15061723.

Abstract

We designed a bioequivalent tablet form of solifenacin succinate (SOL) with an improved storage stability using a direct compression (DC) technique. An optimal direct compressed tablet (DCT) containing an active substance (10 mg), lactose monohydrate, and silicified microcrystalline cellulose as diluents, crospovidone as a disintegrant, and hydrophilic fumed silica as an anti-coning agent was constructed by evaluating the drug content uniformity, mechanical properties, and in vitro dissolution. The physicochemical and mechanical properties of the DCT were as follows: drug content 100.1 ± 0.7%, disintegration time of 6.7 min, over 95% release within 30 min in dissolution media (pH 1.2, 4.0, 6.8, and distilled water), hardness > 107.8 N, and friability ~0.11%. The SOL-loaded tablet fabricated via DC showed an improved stability at 40 °C and RH 75%, exhibiting markedly reduced degradation products compared to those fabricated using ethanol or water-based wet granulation or a marketed product (Vesicare, Astellas Pharma). Moreover, in a bioequivalence study in healthy subjects ( = 24), the optimized DCT offered a pharmacokinetic profile comparable to that of the marketed product, with no statistical differences in the pharmacokinetic parameters. The 90% CIs for the geometric mean ratios of the test to the reference formulation for the area under the curve and the maximum drug concentration in plasma were 0.98-1.05 and 0.98-1.07, respectively, and satisfied the FDA regulatory criteria for bioequivalence. Thus, we conclude that DCT is a beneficial oral dosage form of SOL with an improved chemical stability.

摘要

我们采用直接压片(DC)技术设计了一种具有改善储存稳定性的琥珀酸索利那新(SOL)生物等效片剂形式。通过评估药物含量均匀度、机械性能和体外溶出度,构建了一种最佳的直接压片(DCT),其含有活性物质(10毫克)、一水乳糖和硅化微晶纤维素作为稀释剂,交联聚维酮作为崩解剂,以及亲水性气相二氧化硅作为抗结剂。DCT的物理化学和机械性能如下:药物含量100.1±0.7%,崩解时间6.7分钟,在溶出介质(pH 1.2、4.0、6.8和蒸馏水)中30分钟内释放超过95%,硬度>107.8 N,脆碎度约0.11%。通过DC制备的载有SOL的片剂在40°C和相对湿度75%下显示出改善的稳定性,与使用乙醇或水基湿法制粒制备的片剂或市售产品(卫喜康,安斯泰来制药)相比,降解产物明显减少。此外,在一项针对24名健康受试者的生物等效性研究中,优化后的DCT提供了与市售产品相当的药代动力学特征,药代动力学参数无统计学差异。试验制剂与参比制剂的曲线下面积和血浆中最大药物浓度的几何平均比值的90%置信区间分别为0.98 - 1.05和0.98 - 1.07,满足FDA生物等效性监管标准。因此,我们得出结论,DCT是一种具有改善化学稳定性的有益的SOL口服剂型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2016/10301382/aa4df9608e29/pharmaceutics-15-01723-g001.jpg

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