Bolourchian Noushin, Shafiee Panah Mina
Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2022 May 9;21(1):e126913. doi: 10.5812/ijpr-126913. eCollection 2022 Dec.
The present study mainly aimed to prepare solid dispersions (SDs) of a poorly water-soluble compound, carvedilol (CA), in the presence of pluronic F68 (F68) and myrj 52 by wet milling technique in order to enhance drug dissolution. The process enabled the preparation of SDs without using any toxic organic solvents. SDs with different CA: surfactant ratios were prepared by wet milling followed by freeze-drying method and evaluated for their particle size and dissolution. They were also characterized based on/using X-ray diffraction (XRD), differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), and saturated solubility. The effect of cryoprotectant type on the dissolution and particle size of SDs was also investigated. Wet milling process resulted in the reduced particle size depending on the type of surfactant. The significant drug dissolution and saturated solubility enhancement were recorded for milled SD formulations. In this regard, Myrj had a greater impact compared to F68. Dissolution efficiencies (DE) obtained for the myrj-included SDs were up to 8.2-fold higher than that of untreated CA. The type of cryoprotectant was also found to affect the drug dissolution. According to the results, partial amorphization occurred in wet-milled samples, as confirmed by XRD and DSC analysis. It was concluded that using an appropriate surfactant along with wet-milling method may have been an effective approach for improving the dissolution rate of CA, a poorly soluble compound.
本研究主要目的是在普朗尼克F68（F68）和聚山梨醇酯80存在的情况下，通过湿磨技术制备难溶性化合物卡维地洛（CA）的固体分散体（SDs），以提高药物溶出度。该工艺能够在不使用任何有毒有机溶剂的情况下制备SDs。通过湿磨然后冷冻干燥法制备了不同CA:表面活性剂比例的SDs，并对其粒径和溶出度进行了评估。还基于/使用X射线衍射（XRD）、差示扫描量热法（DSC）、傅里叶变换红外（FTIR）光谱、扫描电子显微镜（SEM）和饱和溶解度对它们进行了表征。还研究了冷冻保护剂类型对SDs溶出度和粒径的影响。湿磨过程导致粒径根据表面活性剂类型而减小。对于研磨后的SD制剂，记录到显著的药物溶出度和饱和溶解度提高。在这方面，与F68相比，聚山梨醇酯80的影响更大。含聚山梨醇酯80的SDs的溶出效率（DE）比未处理的CA高8.2倍。还发现冷冻保护剂类型会影响药物溶出度。根据结果，XRD和DSC分析证实湿磨样品中发生了部分非晶化。得出的结论是，使用合适的表面活性剂并结合湿磨方法可能是提高难溶性化合物CA溶出速率的有效方法。
