Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland.
Faculty of Applied Physic and Mathematics, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland.
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Dec 5;302:123048. doi: 10.1016/j.saa.2023.123048. Epub 2023 Jun 20.
Detection of incompatibility between an active pharmaceutical ingredient (API) and excipients, including the selection of the most biopharmaceutical advantageous excipients is extremely important in the pre-formulation process of developing a solid dosage form technology. Therefore, having fast and reliable methods for identifying incompatibility is fundamental in pharmaceutical technology. For this purpose, combined Fourier transform infrared (FTIR) and Raman spectroscopy as well as high-temperature X-ray diffraction (HT-XRD) were used as a new approach for incompatibility detection, whereas differential scanning calorimetry (DSC) was applied as a reference method. In addition, to facilitate the interpretation of FTIR and Raman data, a multivariate analysis was used - hierarchical cluster analysis (HCA). The tests were carried out in mixtures of naproxen (NPX) with eight selected polymer excipients, mixed at a 1:1 ratio. The results of spectroscopic analyses have shown the physical incompatibility of NPX with methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), sodium starch glycolate (SSG) and sodium carboxymethylcellulose (CMC). HT-XRD studies performed when these mixtures were heated to 156 °C and then cooled to 25 °C showed a decrease in naproxen crystallinity in these mixtures. Furthermore, the results obtained with spectroscopic methods were confirmed by DSC tests and an intrinsic dissolution rate study.
在开发固体制剂技术的制剂前阶段，检测原料药（API）与赋形剂之间的不相容性，包括选择最有利于生物制药的赋形剂，是极其重要的。因此，拥有快速可靠的不相容性鉴定方法是制药技术的基础。为此，将傅里叶变换红外（FTIR）和拉曼光谱以及高温 X 射线衍射（HT-XRD）相结合，作为一种新的不相容性检测方法，而差示扫描量热法（DSC）则作为参考方法。此外，为了便于解释 FTIR 和拉曼数据，还使用了多元分析-层次聚类分析（HCA）。该测试在萘普生（NPX）与 8 种选定的聚合物赋形剂以 1:1 比例混合的混合物中进行。光谱分析的结果表明 NPX 与甲基纤维素（MC）、羟丙基甲基纤维素（HPMC）、羟乙基纤维素（HEC）、交联羧甲基纤维素钠（SSG）和羧甲基纤维素钠（CMC）存在物理不相容性。当将这些混合物加热至 156°C 然后冷却至 25°C 时进行 HT-XRD 研究，表明这些混合物中萘普生的结晶度降低。此外，通过 DSC 测试和内在溶解速率研究证实了光谱方法获得的结果。
