Markovic Nov, Agotonovic-Kustrin Snezana, Glass Beverley, Prestidge Clive A
Ian Wark Research Institute, ARC Special Research Centre, University of South Australia, Mawson Lakes Blvd., Mawson Lakes, SA 5095, Australia.
J Pharm Biomed Anal. 2006 Sep 11;42(1):25-31. doi: 10.1016/j.jpba.2005.12.039. Epub 2006 Mar 9.
The physical properties of drug substances may affect stability, manufacturing, dissolution and bioavailability. Variations in the degree of crystallinity in a pharmaceutical substance may exhibit physicochemical differences that impact at therapeutic, manufacturing, commercial and legal levels, yet no reference has been found on the physical properties of micronised omeprazole. This study reports on the physical and thermal characterisation of the sodium salts of S- and R-omeprazole, using diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), microthermal analysis (microTA) and powder X-ray diffraction (XRPD). DSC experiments were performed in order to determine not only their thermal stability, but also the thermal history of both forms. SEM results indicate similar morphology, particle size and shape of powdered drug, while, microTA of processed discs shows different topographical images for S- and R-omeprazole, exhibiting a smoother surface for the S-form, indicative of the smoother particle size not evident in the SEM results. The low level of crystallinity of both enantiomers was confirmed by DRIFT spectroscopy and XRPD. Thermal stability by DSC of S- and R-omeprazole sodium salts was superior to that of the neutral omeprazole. This study has examined the physical and thermal properties of both forms and in highlighting their differences provides an explanation for the potential differences in bioavailability and therapeutic efficacy.
药物的物理性质可能会影响其稳定性、制造工艺、溶出度和生物利用度。药物中结晶度的变化可能会表现出物理化学差异，这些差异会在治疗、制造、商业和法律层面产生影响，但尚未发现有关微粉化奥美拉唑物理性质的参考文献。本研究报告了使用漫反射红外傅里叶变换光谱（DRIFT）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）、微热分析（microTA）和粉末X射线衍射（XRPD）对S-和R-奥美拉唑钠盐进行物理和热表征的结果。进行DSC实验不仅是为了确定它们的热稳定性，还为了确定两种晶型药物的热历史。SEM结果表明，粉末状药物具有相似的形态、粒径和形状，而处理过的圆片的microTA显示S-和R-奥美拉唑具有不同的表面形貌图像，S型具有更光滑的表面，这表明在SEM结果中未明显体现出更均匀的粒径。DRIFT光谱和XRPD证实了两种对映体的结晶度较低。S-和R-奥美拉唑钠盐的DSC热稳定性优于中性奥美拉唑。本研究考察了两种晶型药物物理和热性质，并突出了它们的差异，为生物利用度和治疗效果的潜在差异提供了解释。
