Purpose

This study aims to demonstrate the continuous and low-cost technique of crystallization with the use of hollow fiber membrane for production and size-controlled ibuprofen drug nanoparticles as a form of nanosuspension for intramuscular applications.

Methods

Hollow fiber porous membrane was applied for antisolvent crystallization procedure. Experimental design using response surface methodology was implemented to capture the effect of major factors on the final size of ibuprofen nanoparticles. The impact of pertinent factors, including the inlet velocity, temperature, and surfactant concentration on drug nanoparticles’ final size, were systematically studied.

Results

Statistical analysis suggested the optimal range of parameters (V = 45 mL/min, C = 0.011 mM, and T = 32 °C) for obtaining drug nanosuspension in a size range of 300–400 nm. In vitro dissolution studies displayed the complete release of the optimized ibuprofen nano-drug takes only 40 min.

Conclusion

According to the results, the desired size-controlled ibuprofen nanosuspension was prepared via this method. The continuous and increased release of the drug can significantly increase its bioavailability. Additionally, the obtained nanosuspension was physically stable over 3 months without any specific particle size and size distribution changes, making them attractive candidates for practical usages. To the best of our knowledge, this is the first report on the continuous preparation of ibuprofen using porous hollow fiber antisolvent crystallization with precise control over the final size of the drug.

中文翻译：

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中空纤维膜反溶剂结晶法连续可控制备布洛芬纳米混悬剂

目的

本研究旨在证明使用中空纤维膜生产和尺寸控制的布洛芬药物纳米粒子作为一种用于肌肉内应用的纳米混悬剂形式的连续且低成本的结晶技术。

方法

中空纤维多孔膜用于抗溶剂结晶过程。使用响应面法进行实验设计，以捕捉主要因素对布洛芬纳米粒子最终尺寸的影响。系统研究了相关因素，包括入口速度、温度和表面活性剂浓度对药物纳米粒子最终尺寸的影响。

结果

 统计分析表明，获得粒径范围为 300-400 nm 的药物纳米混悬剂的最佳参数范围（V  = 45 mL/min，C  = 0.011 mM 和T = 32 °C）。体外溶出研究表明，优化的布洛芬纳米药物的完全释放仅需 40 分钟。

结论

根据结果​​，通过该方法制备了所需的尺寸可控的布洛芬纳米混悬剂。药物的持续和增加释放可以显着提高其生物利用度。此外，所获得的纳米悬浮液在 3 个月内物理稳定，没有任何特定的粒径和尺寸分布变化，使其成为实际应用的有吸引力的候选者。据我们所知，这是第一份关于使用多孔中空纤维反溶剂结晶连续制备布洛芬的报告，并精确控制药物的最终尺寸。