Apixaban and clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Saudi Pharmaceutical Journal Pub Date : 2024-04-29 DOI:10.1016/j.jsps.2024.102089
Ni'meh Al-Shami, Hani Naseef, Feras Kanaze
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Abstract

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release Clopidogrel 75 mg and Extend-Release Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded Clopidogrel and extended-release Apixaban for 24 h with the desired in vitro drug dissolution.

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阿哌沙班和氯吡格雷的固定剂量复方制剂:配方和体外评估
固定剂量复方制剂(FDC)产品是一种新型、安全且具有成本效益的制剂。在合并心血管疾病的患者中,联合使用抗凝药物和抗血小板药物很常见。本研究旨在配制阿哌沙班和氯吡格雷的 FDC 片剂,作为血栓栓塞事件的预防和治疗药物。通过直接压片和湿法制粒,将75毫克速释氯吡格雷和5毫克缓释阿哌沙班的小片组合在一起,开发出了FDC片剂。其中,阿哌沙班片剂的开发使用了设计专家软件,并输入了不同类型和浓度的聚合物。至于氯吡格雷片剂,则使用了各种稀释剂来开发制剂。然后,研究了每个配方的溶出曲线。最后,将优化配方封装在硬明胶胶囊中。阿哌沙班制剂的药物释放机制为零阶超Ⅱ型转运机制。阿哌沙班的药物释放率受制剂中聚合物类型和浓度的影响(P < 0.05)。随着 HPMC 浓度的增加,阿哌沙班的释放速度减慢。至于氯吡格雷,使用喷雾干燥乳糖填充剂和硬脂富马酸钠润滑剂配制的片剂性能稳定。总之,最佳配方可使氯吡格雷和阿哌沙班缓释片在 24 小时内达到理想的体外药物溶出度。
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来源期刊
Saudi Pharmaceutical Journal
Saudi Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
6.10
自引率
2.40%
发文量
194
审稿时长
67 days
期刊介绍: The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.
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