Excellent Center of Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Rajathevee, Bangkok 10400, Thailand; Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevee, Bangkok 10400, Thailand.
Int J Pharm. 2013 Nov 30;457(1):187-96. doi: 10.1016/j.ijpharm.2013.09.022. Epub 2013 Sep 26.
Nanocrystals is one of effective technologies used to improve solubility and dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS class II having low bioavailability due to very low dissolution behavior. The main purpose of this study was to investigate an efficiency of clarithromycin nanocrystals preparation by precipitation-lyophilization-homogenization (PLH) combination method in comparison with high pressure homogenization (HPH) method. The factors influencing particle size reduction and physical stability were assessed. The results showed that the PLH technique provided an effective and rapid reduction of particle size of nanocrystals to 460 ± 10 nm with homogeneity size distribution after only the fifth cycle of homogenization, whereas the same size was attained after 30 cycles by the HPH method. The smallest nanocrystals were achieved by using the combination of poloxamer 407 (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the particle aggregation over 3-month storage at 4 °C. The results from SEM showed that the clarithromycin nanocrystals were in cubic-shaped similar to its initial particle morphology. The DSC thermogram and X-ray diffraction pattern of nanocrystals were not different from the original drug except for intensity of peaks which indicated the presenting of nanocrystals in the crystalline state and/or partial amorphous form. In addition, the dissolution of the clarithromycin nanocrystals was dramatically increased as compared to the coarse clarithromycin.
纳米晶体是一种用于提高难溶性药物溶解度和溶解行为的有效技术之一。克拉霉素被归类为 BCS 分类 II 类药物，由于溶解行为非常低，生物利用度低。本研究的主要目的是研究沉淀-冷冻干燥-均化（PLH）组合法制备克拉霉素纳米晶体的效率，并与高压匀浆（HPH）法进行比较。评估了影响粒径减小和物理稳定性的因素。结果表明，PLH 技术在仅经过第五次匀化循环后，可有效且快速地将纳米晶体的粒径减小至 460±10nm，并具有均匀的粒径分布，而 HPH 方法则需要 30 次循环才能达到相同的粒径。使用泊洛沙姆 407（2%，w/v）和 SLS（0.1%，w/v）作为稳定剂的组合可以防止颗粒在 4°C 下储存 3 个月时聚集。SEM 结果表明，克拉霉素纳米晶体呈立方形状，类似于其初始颗粒形态。纳米晶体的 DSC 热谱和 X 射线衍射图谱与原始药物没有区别，除了峰的强度表明纳米晶体以结晶状态和/或部分无定形形式存在。此外，与粗克拉霉素相比，克拉霉素纳米晶体的溶解显著增加。
