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载头孢泊肟酯自固化固体 SNEDDS 的物理特性表征及体外溶出度评价

Physical Characterization and In Vitro Evaluation of Dissolution Rate from Cefpodoxime Proxetil Loaded Self Solidifying Solid SNEDDS.

机构信息

Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University Uttar Pradesh, 201303, Uttar Pradesh, India.

Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Uttar Pradesh, India.

出版信息

Curr Drug Deliv. 2022;19(3):395-406. doi: 10.2174/1567201818666210805153859.

Abstract

BACKGROUND

Cefpodoxime Proxetil (CPD) is a broad-spectrum cephalosporin indicated in respiratory and urinary tract infections. CPD is a BCS class IV drug with pH-dependent solubility and has poor bioavailability. This study investigated the challenges of developing ternary components based on solid SNEDDS of CPD for in vitro dissolution rate enhancement and self-solidifying behaviour.

METHODS

Tween 80, Transcutol and PEG6000 were employed as surfactants, solvents and solidifiers for a base of ternary components to develop self-solidifying solid SNEDDS, respectively. Ternary phase diagrams were used to characterize solidifying behaviour of ternary components in different proportions. S-SNEDDS formulations were drawn on the solidification areas available in the phase diagram and characterized for IR, XRD, DSC and in vitro drug release in various pH media.

RESULTS

Ternary components for the preparation of self-solidifying solid SNEDDS were selected based on drug solubility. FTIR and DSC characterization studies ruled out any drug interaction between CPD and components chosen to prepare S-SNEDDS. CPD was transformed from a crystalline into an amorphous state in ternary dispersions as revealed from XRD data. Optimized formulation (S-S 1) demonstrated more than 95% of drug release irrespective of the pH environments of the medium. Calculation of dissolution efficiency and similarity factors indicate that S SNEDDS resulted in a higher drug dissolution rate over binary dispersion (p<0.01). The stability studies showed that the S SNEDDS were stable in performances and CPD assay.

CONCLUSION

The present investigation provides an alternative approach for enhancing the CPD dissolution rate using self-solidifying solid SNEDDS exhibited solidification behaviour at ambient temperature conditions and drug loading, which could be exploited over conventional dosage form.

摘要

背景

头孢泊肟酯(CPD)是一种广谱头孢菌素,用于治疗呼吸道和尿路感染。CPD 是一种 BCS 分类为 IV 类的药物,具有 pH 依赖性溶解度和较差的生物利用度。本研究旨在探讨基于 CPD 的固体 SNEDDS 的三元成分开发用于提高体外溶出速率和自固化行为的挑战。

方法

吐温 80、Transcutol 和 PEG6000 分别用作表面活性剂、溶剂和固化剂,用于开发自固化固体 SNEDDS 的三元成分基础。使用三元相图来表征不同比例下三元成分的固化行为。S-SNEDDS 配方绘制在相图中可用的固化区域,并对其进行 IR、XRD、DSC 和不同 pH 介质中的体外药物释放进行表征。

结果

根据药物溶解度选择了用于制备自固化固体 SNEDDS 的三元成分。FTIR 和 DSC 特征研究排除了 CPD 与用于制备 S-SNEDDS 的成分之间的任何药物相互作用。XRD 数据显示,CPD 在三元分散体中从结晶态转变为无定形态。优化配方(S-S1)在无论介质的 pH 环境如何,都能实现超过 95%的药物释放。溶解效率和相似因子的计算表明,S-SNEDDS 比二元分散体具有更高的药物溶解速率(p<0.01)。稳定性研究表明,S-SNEDDS 在性能和 CPD 测定方面均稳定。

结论

本研究提供了一种替代方法,通过自固化固体 SNEDDS 来提高 CPD 的溶解速率,该固体 SNEDDS 在环境温度条件下表现出固化行为,且具有载药量,可替代传统剂型。

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