Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab-160 062, India.
Pharmaceutics. 2011 Aug 25;3(3):525-37. doi: 10.3390/pharmaceutics3030525.
This manuscript studied the effect of counterion on the glass transition and recrystallization behavior of amorphous salts of prazosin. Three amorphous salts of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin tosylate were prepared by spray drying, and characterized by optical-polarized microscopy, differential scanning calorimetry and powder X-ray diffraction. Modulated differential scanning calorimetry was used to determine the glass transition and recrystallization temperature of amorphous salts. Glass transition of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ~ prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed glass transition, followed by recrystallization. In contrast, amorphous prazosin hydrochloride showed glass transition and recrystallization simultaneously. Density Functional Theory, however, suggested the expected order of glass transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The counterintuitive observation of amorphous prazosin hydrochloride having lower glass transition was explained in terms of its lower activation energy (206.1 kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further correlated to a difference in hydrogen bonding strength of the amorphous and the corresponding recrystallized salts. This study has implications in selection of an optimal amorphous salt form for pharmaceutical development.
本文研究了抗衡离子对普萘洛尔无定形盐玻璃化转变和重结晶行为的影响。通过喷雾干燥法制备了普萘洛尔盐酸盐、普萘洛尔甲磺酸盐和普萘洛尔对甲苯磺酸盐三种普萘洛尔无定形盐，并通过偏光显微镜、差示扫描量热法和粉末 X 射线衍射进行了表征。采用调制差示扫描量热法测定了无定形盐的玻璃化转变和重结晶温度。无定形盐的玻璃化转变顺序为：普萘洛尔甲磺酸盐>普萘洛尔对甲苯磺酸盐~普萘洛尔盐酸盐。无定形普萘洛尔甲磺酸盐和普萘洛尔对甲苯磺酸盐先发生玻璃化转变，然后发生重结晶。相比之下，无定形普萘洛尔盐酸盐则同时发生玻璃化转变和重结晶。然而，密度泛函理论预测的玻璃化转变顺序为普萘洛尔盐酸盐>普萘洛尔甲磺酸盐>普萘洛尔对甲苯磺酸盐。无定形普萘洛尔盐酸盐的玻璃化转变较低，这一反直觉的观察结果可以用其在 Tg 时分子迁移的较低活化能（206.1 kJ/mol）来解释，而无定形普萘洛尔甲磺酸盐（448.5 kJ/mol）和普萘洛尔对甲苯磺酸盐（490.7 kJ/mol）则较高，这与无定形盐和相应的重结晶盐的氢键强度差异有关。本研究对选择最佳的无定形盐形式用于药物开发具有重要意义。
