Dichiarante Elena, Curzi Marco, Giaffreda Stefano L, Grepioni Fabrizia, Maini Lucia, Braga Dario
PolyCrystalLine s.r.l., Bologna, Italy.
Dipartimento di Chimica G. Ciamician, University of Bologna, Bologna, Italy.
J Pharm Pharmacol. 2015 Jun;67(6):823-9. doi: 10.1111/jphp.12378. Epub 2015 Feb 3.
To prepare new crystalline forms of the antidepressant o-desmethylvenlafaxine salt as potential new commercial forms and evaluate their physicochemical properties, in particular the dissolution rate.
A new hydrogen oxalate salt of o-desmethylvenlafaxine hydrogen oxalate (ODV-OX) was synthesized, and a polymorph screening was performed using different solvents and crystallization conditions. Crystalline forms were characterized by a combination of solid-state techniques: X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy and single crystal X-ray diffraction. The stability of all crystalline phases was tested under International Conference on Harmonisation (ICH) conditions (40°C and 75% Relative Humidity (RH)) for 1 week. Dissolution tests were performed on the hydrogen oxalate salt ODV-OX Form 1 and compared with dissolution test on the commercial form of the succinate salt of o-desmethylvenlafaxine.
Five crystalline forms of ODV-OX were isolated, namely three hydrated forms (Form 1, Form 2, Form 3) and two anhydrous forms (Form 4 and Form 5).
Comparative solubility tests on ODV-OX Form 1 and o-desmethylvenlafaxine succinate evidenced a significant increase in solubility for the hydrogen oxalate salt (142 g/l) with respect to the succinate salt (70 g/l).
制备抗抑郁药去甲文拉法辛盐的新晶型作为潜在的新商业形式,并评估其物理化学性质,特别是溶出速率。
合成了一种新的去甲文拉法辛草酸氢盐(ODV - OX),并使用不同溶剂和结晶条件进行了多晶型筛选。通过多种固态技术相结合对晶型进行表征:X射线粉末衍射、差示扫描量热法、热重分析、傅里叶变换红外光谱和单晶X射线衍射。在国际协调会议(ICH)条件(40°C和75%相对湿度(RH))下对所有晶相的稳定性进行了1周的测试。对ODV - OX晶型1的草酸盐进行了溶出度测试,并与去甲文拉法辛琥珀酸盐的商业形式的溶出度测试进行了比较。
分离出了ODV - OX的五种晶型,即三种水合形式(晶型1、晶型2、晶型3)和两种无水形式(晶型4和晶型5)。
对ODV - OX晶型1和去甲文拉法辛琥珀酸盐的溶解度比较测试表明,草酸盐(142 g/l)相对于琥珀酸盐(70 g/l)的溶解度有显著增加。