Khan Barkat Ali, Khalid Hina, Khan Muhammad Khalid, Hosny Khaled M, Khan Shahzeb, Rizg Waleed Y, Safhi Awaji Y, Halwani Abdulrahman A, Almehmady Alshaimaa M, Menaa Farid
Drug Delivery and Cosmetic Lab (DDCL), Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Polymers (Basel). 2022 Aug 25;14(17):3464. doi: 10.3390/polym14173464.
Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.
纳米晶体是无载体、亚微米级的胶体药物递送系统，其粒径平均在纳米范围内。由于纳米晶体具有高溶解速度和增强的细胞膜粘附性，因此具有高生物利用度和快速吸收性。洛索洛芬是一种属于生物药剂学分类系统（BCS）II类的非甾体抗炎药，被选作模型药物。本研究的目的是制备洛索洛芬纳米晶体。共制备了12种制剂（F1至F12）。采用抗溶剂技术来确定各种稳定剂和加工条件对制剂优化的影响。使用的各种稳定剂有羟丙基甲基纤维素（0.5%）、聚乙烯吡咯烷酮（0.5%）和十二烷基硫酸钠（0.1%）。本研究进行的各种表征包括在25℃和4℃下的稳定性研究、扫描电子显微镜、透射电子显微镜（TEM）、X射线粉末衍射（XRPD）、差示扫描量热法（DSC）、zeta电位、多分散指数和溶出度研究。F10是优化后的制剂，在室温以及冷藏温度下均显示出30天的稳定性。通过纳米混悬液与微混悬液和原料药洛索洛芬的比较溶出度研究表明，其具有高溶出率（在前10分钟内达到100%）。通过TEM和XRPD评估，F10制剂分别具有无孔和结晶形态，TEM证实其平均粒径为300±0.3nm。DSC记录到熔点降低（加工后的熔点为180℃，未加工的熔点为200℃）。所制备的洛索洛芬纳米晶体的溶出率和溶解度显著提高。可以得出结论，选择合适的稳定剂（即聚合物和表面活性剂）可以制备出稳定的纳米晶体，这有可能导致该工艺扩大规模以实现商业化。
