Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan.
Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan.
Eur J Pharm Sci. 2018 Jan 15;112:139-145. doi: 10.1016/j.ejps.2017.11.016. Epub 2017 Nov 21.
Poor aqueous solubility is often linked with a poor dissolution rate and ultimately, limited bioavailability of pharmaceutical compounds. This study describes the application of mesoporous materials (Syloid 244 and Syloid AL1) in improving the dissolution rate of a drug with poor aqueous solubility, namely artemether, utilising different processing methods including physical mixing, co-grinding and solid dispersions prepared by solvent evaporation and the lyophilisation technique. The prepared formulations were extensively characterised for their solid-state properties and the drug release attributes were studied. Differential scanning calorimetry and X-ray diffraction confirmed conversion of crystalline artemether into a disordered and amorphous form, whilst no intermolecular interactions were detected between artemether and silica. Both silica grades enhanced the dissolution rate of artemether in comparison with drug alone, for example from 17.43% (±0.87%) to 71.55% (±3.57%) after 120mins with lyophilisation and Syloid 244 at a 1:3 ratio. This enhancement was also dependant on the choice of processing method, for example, co-ground and lyophilised formulations prepared with Syloid 244 at 1:3 ratio produced the most extensive dissolution, thus endorsing the importance of materials as well as choice of formulation method.
水溶解度差通常与溶解速率低有关，最终会导致药物的生物利用度有限。本研究描述了中孔材料（Syloid 244 和 Syloid AL1）在改善水溶解度差的药物（即青蒿素）的溶解速率方面的应用，使用了包括物理混合、共研磨以及溶剂蒸发和冷冻干燥技术制备的固体分散体在内的不同加工方法。对制备的制剂进行了广泛的固态特性表征，并研究了药物释放特性。差示扫描量热法和 X 射线衍射证实，结晶青蒿素转化为无定形和无定形形式，而青蒿素和二氧化硅之间未检测到分子间相互作用。与单独的药物相比，两种二氧化硅等级均提高了青蒿素的溶解速率，例如，在 120 分钟后，冻干和 1:3 比例的 Syloid 244 使青蒿素的溶解速率从 17.43%（±0.87%）提高到 71.55%（±3.57%）。这种增强还取决于加工方法的选择，例如，以 1:3 的比例共研磨和冻干的制剂用 Syloid 244 制备，可产生最广泛的溶解，因此证实了材料的重要性以及制剂方法的选择。
