Wu Carina Yeeka, Wang Wei
Center for Pharmacy & Department of Chemistry, University of Bergen, 5020 Bergen, Norway.
Pharmaceutics. 2022 Apr 8;14(4):819. doi: 10.3390/pharmaceutics14040819.
The aim of the present study was to systematically examine the effects of variations in the process parameters of the antisolvent precipitation method employed in the preparation of excipient-free pure nanoparticles of five existing/potential psychotropic drugs, namely amitriptyline hydrochloride (AMI), coumarin 6 (COU), curcumin (CUR), nortriptyline hydrochloride (NOR), and prochlorperazine dimaleate (PRO). In the preparation protocols employed, AMI and NOR were expected to be charged enough to be identified as surface-active molecules. Through the employment of five different preparation protocols, the effects of varying the flow rate, the compound concentration in the solvent solution C0solvent, the solvent:antisolvent ratio (SAS-ratio), and pH of the antisolvent on the final size of the particles DHf were investigated in detail and the results were explained using available theories for the antisolvent precipitation method. We found that DHf increased with the average of the octanol-water partition coefficients (log) of the compound. Moreover, the average of the final particle sizes (DHf)av increased linearly with (log). These findings are useful for predicting the size of nanodrugs prepared through the antisolvent precipitation method.
本研究的目的是系统地研究在制备五种现有/潜在精神药物（即盐酸阿米替林（AMI）、香豆素6（COU）、姜黄素（CUR）、盐酸去甲替林（NOR）和马来酸丙氯拉嗪（PRO））的无辅料纯纳米颗粒时，反溶剂沉淀法工艺参数变化的影响。在所采用的制备方案中，预计AMI和NOR带电量足以被识别为表面活性分子。通过采用五种不同的制备方案，详细研究了流速、溶剂溶液中化合物浓度C0溶剂、溶剂与反溶剂比例（SAS比例）以及反溶剂pH值对最终颗粒尺寸DHf的影响，并利用反溶剂沉淀法的现有理论对结果进行了解释。我们发现，DHf随化合物的辛醇-水分配系数（log）的平均值增加而增加。此外，最终粒径（DHf）av的平均值与（log）呈线性增加。这些发现有助于预测通过反溶剂沉淀法制备的纳米药物的尺寸。
