Chemical and Synthetic Development, Bristol-Myers Squibb, Co., One Squibb Dr., New Brunswick, NJ 08901, United States.
Drug Product Science & Technology, Bristol-Myers Squibb, Co., One Squibb Dr., New Brunswick, NJ 08901, United States.
Int J Pharm. 2019 Jul 20;566:500-512. doi: 10.1016/j.ijpharm.2019.05.054. Epub 2019 May 23.
We present here the development of a photochemical model used to quantify the risk to photodegradation of a solid drug substance. A key feature of the proposed model development is streamlined estimation of the dependence of the absorption spectra and the quantum yield to the wavelength. A mathematical description of the relationship between the quantum yield and the wavelength enables estimation of photodegradation kinetics under any light anticipated to be encountered in the manufacturing environment. The system studied here consisted of a first order irreversible transformation (A → B(1Φ)) and the formalism strongly suggested the quantum yield was constant over the relevant wavelength range. The predictive power of the model enabled the design of a control strategy to limit the formation of the photo-degradant to very low levels. Also presented are insights obtained from quantum mechanical modeling of the electronic transitions associated with the UV absorption spectra.
我们在此介绍一种光化学反应模型的开发，该模型用于量化固体药物物质光降解的风险。所提出的模型开发的一个关键特征是简化了对吸收光谱和量子产率对波长的依赖性的估计。量子产率与波长之间关系的数学描述可用于在制造环境中预期遇到的任何光下估计光降解动力学。这里研究的系统由一级不可逆转化（A→B（1Φ））组成，该形式主义强烈表明量子产率在相关波长范围内保持恒定。该模型的预测能力使设计一种控制策略成为可能，以将光降解产物的形成限制在非常低的水平。本文还介绍了通过与紫外吸收光谱相关的电子跃迁的量子力学建模获得的见解。
