Wlodarski K, Sawicki W, Paluch K J, Tajber L, Grembecka M, Hawelek L, Wojnarowska Z, Grzybowska K, Talik E, Paluch M
Medical University of Gdansk, Department of Physical Chemistry, Hallera 107, 80-416 Gdansk, Poland.
Medical University of Gdansk, Department of Physical Chemistry, Hallera 107, 80-416 Gdansk, Poland.
Eur J Pharm Sci. 2014 Oct 1;62:132-40. doi: 10.1016/j.ejps.2014.05.026. Epub 2014 Jun 5.
This study for the first time investigates the solubility and dissolution rate of amorphous tadalafil (Td)--a poorly water soluble chemical compound which is commonly used for treating the erectile dysfunction. To convert the crystalline form of Td drug to its amorphous counterpart we have employed most of the commercially available amorphization techniques i.e. vitrification, cryogenic grinding, ball milling, spray drying, freeze drying and antisolvent precipitation. Among the mentioned methods only quenched cooling of the molten sample was found to be an inappropriate method of Td amorphization. This is due to the thermal decomposition of Td above 200°C, as proved by the thermogravimetric analysis (TGA). Disordered character of all examined samples was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (PXRD). In the case of most amorphous powders, the largest 3-fold increase of apparent solubility was observed after 5 min, indicating their fast recrystallization in water. On the other hand, the partially amorphous precipitate of Td and hypromellose enhanced the solubility of Td approximately 14 times, as compared with a crystalline substance, which remained constant for half an hour. Finally, disk intrinsic dissolution rate (DIDR) of amorphous forms of Td was also examined.
本研究首次对非晶态他达拉非（Td）的溶解度和溶解速率进行了研究。他达拉非是一种水溶性较差的化合物，常用于治疗勃起功能障碍。为了将Td药物的结晶形式转化为非晶态形式，我们采用了大多数市售的非晶化技术，即玻璃化、低温研磨、球磨、喷雾干燥、冷冻干燥和抗溶剂沉淀。在上述方法中，仅发现对熔融样品进行骤冷是一种不合适的Td非晶化方法。这是由于热重分析（TGA）证明，Td在200°C以上会发生热分解。使用差示扫描量热法（DSC）和X射线粉末衍射（PXRD）确认了所有测试样品的无序特征。在大多数非晶态粉末的情况下，5分钟后表观溶解度最大增加了3倍，表明它们在水中快速重结晶。另一方面，与晶体物质相比，Td和羟丙甲纤维素的部分非晶态沉淀物使Td的溶解度提高了约14倍，且在半小时内保持恒定。最后，还研究了Td非晶态形式的圆盘固有溶解速率（DIDR）。
