Drug Product Science & Technology, Bristol-Myers Squibb, Co., One Squibb Dr., New Brunswick, NJ 08901, USA.
Chemical and Synthetic Development, Bristol-Myers Squibb, Co., One Squibb Dr., New Brunswick, NJ 08901, USA.
Eur J Pharm Biopharm. 2017 Nov;120:63-72. doi: 10.1016/j.ejpb.2017.08.010. Epub 2017 Aug 20.
Photochemical kinetic models to describe the solution phase degradation of pharmaceutical compounds have been extensively reported, but formalisms applicable to the solid phase under polychromatic light have not received as much attention. The objective of this study was to develop a mathematical model to describe the solid state photodegradation of pharmaceutical powder materials under different area/volumetric scales and light exposure conditions. The model considered the previous formalism presented for photodegradation kinetics in solution phase with important elements applied to static powder material being irradiated with a polychromatic light source. The model also included the influence of optical phenomena (i.e. reflectance, scattering factors, etc.) by applying Beer-Lambert law to light attenuation, including effects of powder density. Drug substance and drug product intermediates (blends and tablet cores) were exposed to different light sources and intensities. The model reasonably predicted the photodegradation levels of powder beds of drug substance and drug product intermediates under white and yellow lights with intensities around 5-11kLux. Importantly, the model estimates demonstrated that the reciprocity law for photoreactions was held. Further model evaluation showed that, due to light attenuation, the powder bed is in virtual darkness at cake depths greater than 500μm. At 100μm, the photodegradation of the investigated compound is expected to be close to 100% in 10days under white fluorescent halophosphate light at 9.5kLux. For tablets, defining the volume over exposed surface area ratio is more challenging. Nevertheless, the model can consider a bracket between worst and best cases to provide a reasonable photodegradation estimate. This tool can be significantly leveraged to simulate different light exposure scenarios while assessing photostability risk in order to define appropriate control strategy in manufacturing.
已经有大量报道描述了用于描述药物化合物溶液相降解的光化学反应动力学模型，但适用于多色光下固相的形式体系尚未得到太多关注。本研究的目的是开发一种数学模型，以描述在不同的面积/体积比和光照条件下药物粉末材料的固态光降解。该模型考虑了之前在溶液相中光降解动力学提出的形式体系，其中包含应用于静态粉末材料的重要元素，该粉末材料由多色光源辐照。该模型还通过将 Beer-Lambert 定律应用于包括粉末密度在内的光衰减，包括光学现象（例如反射率、散射因子等）的影响。药物物质和药物产品中间体（混合物和片剂芯）暴露于不同的光源和强度下。该模型合理地预测了药物物质和药物产品中间体粉末床在强度约为 5-11kLux 的白光和黄光下的光降解水平。重要的是，模型估计表明光反应的互易律成立。进一步的模型评估表明，由于光衰减，在蛋糕深度大于 500μm 时，粉末床处于虚拟黑暗中。在 100μm 处，在 9.5kLux 的白色荧光卤磷酸盐灯下，在 10 天内，所研究化合物的光降解预计接近 100%。对于片剂，定义暴露表面积体积比更具挑战性。尽管如此，该模型可以考虑最坏情况和最佳情况之间的范围，以提供合理的光降解估计。该工具可以在评估光稳定性风险时显著利用不同的光照场景，以确定制造中适当的控制策略。
