含苯磺酸氨氯地平的改良固定剂量联合降压片的研制与评价:生物等效性与稳定性研究。

IF 5.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Hyeon Woo Moon, Jin-Hyuk Jeong, Chun-Woong Park
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引用次数: 0

摘要

背景/目的:奥美沙坦、苯磺酸氨氯地平、氢氯噻嗪等固定剂量联合降压药被广泛应用于原发性高血压的治疗。虽然外消旋氨氯地平有效,但同时含有活性S(-)-氨氯地平和非活性R(+)-氨氯地平的使用与剂量依赖性不良反应相关,如外周水肿。s -氨氯地平是一种具有药理活性的对映体,其降压效果只有原来的一半,副作用发生率更低。方法:本研究采用s -氨氯地平替代外消旋氨氯地平,在提高耐受性的同时保持治疗效果,研制了一种改良的氟氯地平配方。结果:采用双层片剂设计,最大限度地减少了杂质的形成,保证了处方的稳定性,并在应力和加速条件下得到了证实。体外溶出度测试证明与上市参考FDC药物等效,体内药代动力学研究证实生物等效性。结论:这些结果表明,新开发的含苯磺酸s -氨氯地平FDC片是现有奥美沙坦/氨氯地平/氢氯噻嗪联合用药的可行替代方案,具有相当的疗效和药代动力学特性,并有可能提高高血压治疗的安全性和患者依从性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Development and Evaluation of a Modified Fixed-Dose Combination Antihypertensive Tablet Containing S-Amlodipine Besylate: A Bioequivalence and Stability Study.

Development and Evaluation of a Modified Fixed-Dose Combination Antihypertensive Tablet Containing S-Amlodipine Besylate: A Bioequivalence and Stability Study.

Development and Evaluation of a Modified Fixed-Dose Combination Antihypertensive Tablet Containing S-Amlodipine Besylate: A Bioequivalence and Stability Study.

Development and Evaluation of a Modified Fixed-Dose Combination Antihypertensive Tablet Containing S-Amlodipine Besylate: A Bioequivalence and Stability Study.

Background/Objectives: Fixed-dose combination (FDC) antihypertensive medications containing olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide are widely used for the treatment of essential hypertension. Although effective, the use of racemic amlodipine, which contains both active S(-)-amlodipine and inactive R(+)-amlodipine, has been associated with dose-dependent adverse effects, such as peripheral edema. S-amlodipine, a pharmacologically active enantiomer, provides comparable antihypertensive efficacy at half the dose with a lower incidence of side effects. Methods: In this study, a modified FDC formulation was developed by replacing racemic amlodipine with S-amlodipine to enhance tolerability while maintaining therapeutic efficacy. Results: A bilayer tablet design was employed to minimize the formation of impurities and ensure formulation stability, which was confirmed under stress and accelerated conditions. In vitro dissolution testing demonstrated pharmaceutical equivalence with the marketed reference FDC, and an in vivo pharmacokinetic study confirmed bioequivalence. Conclusions: These results suggest that the newly developed S-amlodipine besylate-containing FDC tablet is a viable alternative to existing olmesartan/amlodipine/hydrochlorothiazide combinations, offering comparable efficacy and pharmacokinetic properties with the potential for improved safety and patient adherence in the management of hypertension.

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来源期刊
Pharmaceutics
Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍: Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications,  and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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