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一种用于口服给药的阿瑞匹坦新型半固体自乳化制剂:体外评价

A Novel Semi-Solid Self-Emulsifying Formulation of Aprepitant for Oral Delivery: An In Vitro Evaluation.

作者信息

Nazlı Hakan, Mesut Burcu, Akbal-Dağıstan Özlem, Özsoy Yıldız

机构信息

Department of Pharmaceutical Technology, Trakya University, 22030 Edirne, Turkey.

Department of Pharmaceutical Technology, Istanbul University, 34116 Istanbul, Turkey.

出版信息

Pharmaceutics. 2023 May 16;15(5):1509. doi: 10.3390/pharmaceutics15051509.

Abstract

Aprepitant is the first member of a relatively new antiemetic drug class called NK receptor antagonists. It is commonly prescribed to prevent chemotherapy-induced nausea and vomiting. Although it is included in many treatment guidelines, its poor solubility causes bioavailability issues. A particle size reduction technique was used in the commercial formulation to overcome low bioavailability. Production with this method consists of many successive steps that cause the cost of the drug to increase. This study aims to develop an alternative, cost-effective formulation to the existing nanocrystal form. We designed a self-emulsifying formulation that can be filled into capsules in a melted state and then solidified at room temperature. Solidification was achieved by using surfactants with a melting temperature above room temperature. Various polymers have also been tested to maintain the supersaturated state of the drug. The optimized formulation consists of Capryol 90, Kolliphor CS20, Transcutol P, and Soluplus; it was characterized by DLS, FTIR, DSC, and XRPD techniques. A lipolysis test was conducted to predict the digestion performance of formulations in the gastrointestinal system. Dissolution studies showed an increased dissolution rate of the drug. Finally, the cytotoxicity of the formulation was tested in the Caco-2 cell line. According to the results, a formulation with improved solubility and low toxicity was obtained.

摘要

阿瑞匹坦是一种相对较新的名为NK受体拮抗剂的止吐药物类别的首个成员。它通常被开处方用于预防化疗引起的恶心和呕吐。尽管它被纳入了许多治疗指南,但其溶解度差导致了生物利用度问题。商业制剂中使用了一种粒径减小技术来克服低生物利用度。用这种方法生产包括许多连续步骤,这导致药物成本增加。本研究旨在开发一种替代现有纳米晶体形式的、具有成本效益的制剂。我们设计了一种自乳化制剂,它可以在熔融状态下填充到胶囊中,然后在室温下固化。通过使用熔点高于室温的表面活性剂来实现固化。还测试了各种聚合物以维持药物的过饱和状态。优化后的制剂由辛酸癸酸甘油三酯90、聚氧乙烯蓖麻油CS20、二乙二醇单乙基醚和固体分散体聚合物组成;通过动态光散射、傅里叶变换红外光谱、差示扫描量热法和X射线粉末衍射技术对其进行了表征。进行了脂解试验以预测制剂在胃肠道系统中的消化性能。溶出度研究表明药物的溶出速率增加。最后,在Caco-2细胞系中测试了该制剂的细胞毒性。根据结果,获得了一种具有改善的溶解度和低毒性的制剂。

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