Vrecer F, Vrbinc M, Meden A
Krka, d.d., Novo mesto, R&D Division, Smarjeska cesta 6, 8501, Novo mesto, Slovenia.
Int J Pharm. 2003 Apr 30;256(1-2):3-15. doi: 10.1016/s0378-5173(03)00057-7.
Piroxicam polymorphism was extensively studied in the past. The objective of the present work was to evaluate polymorphism of piroxicam once again and to characterize the obtained crystal forms. Three polymorphic forms and one monohydrate form were obtained by crystallization from saturated solutions in various solvents. Polarity of solvents and crystallization rate defined by temperature of crystallization were found to be critical parameters in determining the polymorphic form. A new polymorphic form designated as form III was obtained by forced crystallization using dry ice. Only form I with the highest melting point was found to be stable under mechanical and thermal stress. Differences in IR spectra were attributed mainly to the differences in number and positions of H-bonds in the piroxicam crystal forms. Slow crystallization of piroxicam from absolute ethanol solution resulted in a mixture of form II and monohydrate. Crystal structure analysis proved that form II represents form alpha(2) already proposed in the literature. Differences in dissolution rates among crystal forms of piroxicam were attributed to differences in their wettability, where highest wettability was obtained for monohydrate and the lowest for form III.
吡罗昔康多晶型在过去已得到广泛研究。本工作的目的是再次评估吡罗昔康的多晶型,并对所获得的晶型进行表征。通过在各种溶剂中从饱和溶液结晶,得到了三种多晶型形式和一种一水合物形式。发现溶剂的极性和由结晶温度定义的结晶速率是决定多晶型形式的关键参数。通过使用干冰强制结晶获得了一种新的多晶型形式,指定为III型。仅发现熔点最高的I型在机械和热应力下是稳定的。红外光谱的差异主要归因于吡罗昔康晶型中氢键数量和位置的差异。从无水乙醇溶液中缓慢结晶吡罗昔康会产生II型和一水合物的混合物。晶体结构分析证明,II型代表文献中已提出的α(2)型。吡罗昔康晶型之间溶解速率的差异归因于它们润湿性的差异,其中一水合物的润湿性最高,III型最低。