College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000 China.
College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000 China.
Eur J Pharm Sci. 2023 Sep 1;188:106503. doi: 10.1016/j.ejps.2023.106503. Epub 2023 Jun 18.
Two new salt forms of sulfadiazine (SDZ) and piperazine (PIP) were synthesized and characterized. Out of the two polymorphs (SDZ-PIP Ⅰ and SDZ-PIP II), SDZ-PIP Ⅱ is the more stable form at low temperature, room temperature and high temperature. The solution-mediated phase transformation result shows that SDZ-PIP II can transform into pure SDZ within 15 s in phosphate buffer at 37 °C, which leads to a loss in solubility advantage. The addition of 2 mg/mL PVP K30, a polymeric crystallization inhibitor, maintains the solubility advantage and permits supersaturation for a longer period of time. SDZ-PIP II showed 2.5 times the solubility of SDZ alone. The area under the curve (AUC) of SDZ-PIP II with 2 mg/mL PVP K30 was approximately 165% of that of SDZ alone. Moreover, SDZ-PIP II with PVP K30 was more effective than SDZ alone in treating meningitis. Therefore, the SDZ-PIP II salt improves the solubility, bioavailability, and anti-meningitis activity of SDZ.
合成并表征了磺胺嘧啶（SDZ）和哌嗪（PIP）的两种新盐形式。在这两种多晶型物（SDZ-PIP I 和 SDZ-PIP II）中，SDZ-PIP II 在低温、室温、高温下都是更稳定的形式。溶液介导的相转变结果表明，在 37°C 的磷酸盐缓冲液中，SDZ-PIP II 可以在 15 秒内转化为纯 SDZ，从而导致溶解度优势丧失。添加 2mg/mL 的 PVP K30（一种聚合物结晶抑制剂）可以保持溶解度优势并允许更长时间的过饱和度。SDZ-PIP II 的溶解度是 SDZ 单独存在时的 2.5 倍。含有 2mg/mL PVP K30 的 SDZ-PIP II 的曲线下面积（AUC）大约是 SDZ 单独存在时的 165%。此外，含有 PVP K30 的 SDZ-PIP II 比 SDZ 单独使用在治疗脑膜炎方面更有效。因此，SDZ-PIP II 盐提高了 SDZ 的溶解度、生物利用度和抗脑膜炎活性。
