Volitaki Charitini, Lewis Andrew, Craig Duncan Q M, Buanz Asma
School of Pharmacy, Faculty of Life Sciences, UCL, 29-39 Brunswick Square, London WC1N 1AX, UK.
Quotient Sciences, Mere Way, Ruddington, Nottingham NG11 6JS, UK.
Pharmaceutics. 2024 Aug 22;16(8):1102. doi: 10.3390/pharmaceutics16081102.
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.
介孔二氧化硅颗粒（MSPs）已被研究作为潜在载体，通过物理稳定负载药物的无定形性质来提高难溶性药物的表观溶解度和溶解速率。在制备此类体系时，人们认识到负载方法对药物的物理状态和性能有至关重要的影响。迄今为止，关于使用电喷雾法将药物负载到介孔二氧化硅中的研究非常有限。在本研究中，我们进一步探索这种方法的应用，特别是作为一种制备无定形且高载药量MSPs的手段；该研究包括考察药物负载量和MSP浓度对制剂性能及过程的影响。与更广泛使用的负载技术旋转蒸发法进行了比较，以评估电喷雾法的相对有效性。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。通过比较体外药物释放试验测定药物释放曲线。即使在高载药量下，电喷雾法也成功制备出了含有无定形药物的制剂。相比之下，虽然通过旋转蒸发法制备的低载药量制剂中的伊曲康唑呈无定形状态，但在高载药量时药物呈结晶状态。除了通过旋转蒸发法制备的最高载药量（结晶）制剂外，所有制剂的药物释放百分比相比纯伊曲康唑提高了多达十倍。通过电喷雾法制备的负载量高达30 mg/mL伊曲康唑的制剂保持了至少六小时的过饱和状态。总体而言，本研究结果表明，电喷雾法能够在高载药量下制备出具有无定形药物的MSPs，并具有相关的良好释放特性。与标准旋转蒸发法的比较表明，电喷雾法在制备更高载药量的无定形材料方面可能更有效。
