已经研究了介孔二氧化硅颗粒(MSP)作为潜在的载体,通过物理稳定负载药物的无定形性质来增加水溶性差的药物的表观溶解度和溶解速率。在准备这样的系统时,应当认识到,装载方法对药物的物理状态和性能具有关键影响。迄今为止,关于使用电喷雾将药物加载到介孔二氧化硅中的研究非常有限。在这项研究中,我们进一步探索这种方法的使用,特别是作为生产无定形和高载药MSP的手段;该研究包括研究载药量和MSP浓度对制剂性能和工艺的影响。与旋转蒸发的比较,一种更广泛使用的加载技术,进行评估电喷雾的相对有效性。使用粉末X射线衍射(PXRD)和差示扫描量热法(DSC)评估制剂中药物的物理状态。通过比较的体外药物释放试验确定药物释放曲线。即使在高载药量下,电喷雾也成功地产生含有无定形药物的制剂。相比之下,而伊曲康唑以无定形形式存在于通过旋转蒸发产生的较低药物负载的制剂中,药物在较高的载量下处于结晶状态。除了通过旋转蒸发制备的最高负载(结晶)制剂之外,与纯伊曲康唑相比,所有制剂的药物释放百分比增加了高达10倍。通过负载有通过电喷雾产生的高达30mg/mL伊曲康唑的制剂维持过饱和至少6小时。总的来说,这项研究的结果表明,电喷雾能够在高载量下产生无定形载药MSP,具有相关的有利释放特性。与标准旋转蒸发方法的比较表明,电喷雾对于生产更高负载量的无定形材料可能更有效。
Mesoporous silica particles (MSPs) have been investigated as potential carriers to increase the apparent solubility and dissolution rate of poorly water-soluble drugs by physically stabilising the amorphous nature of the loaded drug. In preparing such systems, it is recognized that the loading method has a critical impact on the physical state and performance of the drug. To date, there has been very limited investigation into the use of
electrospraying for loading drugs into mesoporous silica. In this study, we further explore the use of this approach, in particular as a means of producing amorphous and high drug-loaded MSPs; the study includes an investigation of the effect of drug loading and MSP concentration on the formulation performance and process. A comparison with rotary evaporation, a more widely utilised loading technique, was conducted to assess the relative effectiveness of electrospraying. The physical state of the drug in the formulations was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The drug release profiles were determined by a comparative in vitro drug release test.
Electrospraying successfully produced formulations containing amorphous drug even at a high drug loading. In contrast, while itraconazole was present in amorphous form at the lower drug-loaded formulations produced by rotary evaporation, the drug was in the crystalline state at the higher loadings. The percentage of drug released was enhanced up to ten times compared to that of pure itraconazole for all the formulations apart from the highest loaded (crystalline) formulation prepared by rotary evaporation. Supersaturation for at least six hours was maintained by the formulations loaded with up to 30 mg/mL itraconazole produced by
electrospraying. Overall, the results of this study demonstrate that
electrospraying is capable of producing amorphous drug-loaded MSPs at high loadings, with associated favourable release characteristics. A comparison with the standard rotary evaporation approach indicates that
electrospraying may be more effective for the production of higher loadings of amorphous material.