Purpose

The study was aimed at exploring the feasibility of LIPOID SPC-3 as a coprecipitate carrier to enhance the aqueous solubility and permeability of ranolazine, a BCS class II drug.

Methods

LIPOID SPC-3-based coprecipitates of ranolazine (RNZ-SPC-CP) were developed using the solvent method. The developed formulation was physico-chemically characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder x-ray diffractometry (PXRD), and drug content. Functional evaluation of RNZ-SPC-CP formulations was carried out by solubility analysis, in vitro dissolution studies, fed vs. fasted state dissolution comparison, and ex vivo permeation studies.

Results

The SEM studies revealed dissimilar morphological characteristics of pure ranolazine, LSPC-3, and RNZ-SPC-CP formulations. The physico-chemical analysis confirmed the formation of the coprecipitate. Optimized RNZ-SPC-CP1 demonstrated a noteworthy increase (~ 18-fold) in water solubility (~ 92.23 ± 1.02 μg/mL) over that of pure ranolazine (~ 4.94 ± 0.06 μg/mL) and physical mixture (PM) (~ 30.21 ± 2.12 μg/mL). Optimized RNZ-SPC-CP1 appreciably enhanced the rate and extent of ranolazine dissolution (~ 85%), compared with that of pure ranolazine (~ 21%) and PM (~ 35%). Similarly, the permeation rate of ranolazine from optimized RNZ-SPC-CP1 formulation was found to be enhanced significantly (~ 83%) over that of pure ranolazine (~ 19%) and PM (~ 32%). In the fed state, the RNZ-SPC-CP1 improved the rate and extent of ranolazine dissolution, compared with those of fasted state dissolution.

Conclusions

The results conclude that RNZ-SPC-CP could be used as a promising approach for enhancing the aqueous solubility and permeation rate of ranolazine.

中文翻译：

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基于LIPOID SPC-3的共沉淀物可增强雷诺嗪的水溶性和渗透性

目的

这项研究的目的是探索LIPOID SPC-3作为共沉淀载体来增强BCS II类药物雷诺嗪的水溶性和渗透性的可行性。

方法

使用溶剂法开发了基于LIPOID SPC-3的雷诺嗪共沉淀物（RNZ-SPC-CP）。使用扫描电子显微镜（SEM），差示扫描量热法（DSC），傅立叶变换红外光谱（FT-IR），粉末X射线衍射法（PXRD）和药物含量对所开发的制剂进行物理化学表征。RNZ-SPC-CP制剂的功能评估通过溶解度分析，体外溶出度研究，进食与禁食状态溶出度比较以及离体渗透研究进行。

结果

SEM研究显示纯雷诺嗪，LSPC-3和RNZ-SPC-CP配方具有不同的形态特征。物理化学分析证实了共沉淀物的形成。优化的RNZ-SPC-CP1与纯雷诺嗪（〜4.94±0.06μg/ mL）和物理混合物（PM）相比，水溶性（〜92.23±1.02μg/ mL）显着增加（〜18倍） 30.21±2.12μg/ mL）。与纯雷诺嗪（〜21％）和PM（〜35％）相比，优化的RNZ-SPC-CP1显着提高了雷诺嗪的溶解速度和程度（〜85％）。类似地，发现优化的RNZ-SPC-CP1配方的雷诺嗪的渗透率比纯雷诺嗪（〜19％）和PM（〜32％）显着提高（〜83％）。在进食状态下，RNZ-SPC-CP1改善了雷诺嗪的溶解速度和程度，

结论

结果表明，RNZ-SPC-CP可作为提高雷诺嗪的水溶性和渗透率的有前途的方法。