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基于磷酰酯的扎托洛芬固体自纳米乳化药物递送系统的制剂与药代动力学评价

Formulation and Pharmacokinetic Evaluation of Phosal Based Zaltoprofen Solid Self-Nanoemulsifying Drug Delivery System.

作者信息

Kalamkar Rajan, Wadher Shailesh

机构信息

School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri, Nanded, Maharashtra, India.

出版信息

Pharm Nanotechnol. 2019;7(4):328-338. doi: 10.2174/2211738507666190802141754.

Abstract

BACKGROUND

Phosal based excipients are liquid concentrates containing phospholipids. They are used to solubilize water-insoluble drug and also act as an emulsifier to get the smallest droplet size of the formed emulsion after administration.

OBJECTIVE

The aim is to prepare phosal based self nanoemulsifying drug delivery system (SNEDDS) for water insoluble drug zaltoprofen.

METHODS

The various parameters like solubility of drug in different vehicles, ternary phase diagram are considered to formulate the stable emulsion which is further characterized by Self emulsification time and globule size analysis to optimize liquid SNEDDS of Zaltoprofen. Optimized L-SNEDDS was converted into free-flowing powder Solid-SNEDDS (S-SNEDDS). S-SNEDDS was evaluated for Globule size analysis after reconstitution, in vitro dissolution study and in vivo pharmacokinetic study in rats.

RESULTS

Phosal 53 MCT with highest drug solubility was used as oil along with Tween 80 and PEG 400 as surfactant and cosurfactant respectively to prepare liquid SNEDDS. Neusilin us2 was used as an adsorbent to get free-flowing S-SNEDDS. S-SNEDDS showed improved dissolution profile of the drug as compared to pure drug. In vivo study demonstrated that there is a significant increase in Cmax and AUC of S-SNEDDS compared to zaltoprofen powder.

CONCLUSION

Phosal based SNEDDS formation can be successfully used to improve the dissolution and oral bioavailability of poorly soluble drug zaltoprofen.

摘要

背景

基于磷脂的辅料是含有磷脂的液体浓缩物。它们用于溶解水不溶性药物,并且还作为乳化剂,以使给药后形成的乳液具有最小的液滴尺寸。

目的

旨在制备用于水不溶性药物扎托洛芬的基于磷脂的自纳米乳化药物递送系统(SNEDDS)。

方法

考虑药物在不同载体中的溶解度、三元相图等各种参数来配制稳定的乳液,通过自乳化时间和球粒尺寸分析进一步表征,以优化扎托洛芬的液体SNEDDS。将优化后的L-SNEDDS转化为自由流动的粉末状固体SNEDDS(S-SNEDDS)。对S-SNEDDS进行重构后的球粒尺寸分析、体外溶出研究和大鼠体内药代动力学研究。

结果

使用药物溶解度最高的Phosal 53 MCT作为油相,分别使用吐温80和聚乙二醇400作为表面活性剂和助表面活性剂来制备液体SNEDDS。用Neusilin us2作为吸附剂来获得自由流动的S-SNEDDS。与纯药物相比,S-SNEDDS显示出改善的药物溶出曲线。体内研究表明,与扎托洛芬粉末相比,S-SNEDDS的Cmax和AUC有显著增加。

结论

基于磷脂的SNEDDS的形成可成功用于改善难溶性药物扎托洛芬的溶出度和口服生物利用度。

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