Stroyer A, McGinity J W, Leopold C S
College of Pharmacy, University of Texas at Austin, TX, USA.
J Pharm Sci. 2006 Jun;95(6):1342-53. doi: 10.1002/jps.20450.
The influence of the acidic film formers Eudragit L 100, HPMCAS-HF, HP-55, and shellac on the stability of the acid-labile proton pump inhibitor omeprazole in solid drug-polymer blends at accelerated storage conditions (40 degrees C/75% RH) was determined by fourier transform infrared spectroscopy (FTIR), modulated temperature differential scanning calorimetry (MTDSC), and high performance liquid chromatography (HPLC). As expected, acidic polymers caused a degradation of omeprazole which was manifested by discolorations and increasing amounts of degradation products. However, MTDSC curves and FTIR spectra did not show additional peaks resulting from the omeprazole degradation products. These methods appeared to be not sensitive enough to separate analytically the drug and polymer signals from those of the decomposition products. With HPLC a sufficient quantification of the degradation products was possible. HP-55 caused the highest degree of omeprazole degradation, followed by shellac, HPMCAS-HF, and Eudragit L 100. No correlation with the microenvironmental pH values generated by the acidic polymers at the applied storage conditions was found. The melting process and the dissolution of acidic impurities were figured out as possible reasons for the more pronounced decomposition of the drug in presence of HP-55 and shellac.
通过傅里叶变换红外光谱（FTIR）、调制温度差示扫描量热法（MTDSC）和高效液相色谱法（HPLC），测定了酸性成膜剂尤特奇L 100、羟丙甲纤维素醋酸琥珀酸酯-高取代度（HPMCAS-HF）、HP-55和虫胶在加速储存条件（40℃/75%相对湿度）下对固体药物-聚合物混合物中酸不稳定质子泵抑制剂奥美拉唑稳定性的影响。正如预期的那样，酸性聚合物导致奥美拉唑降解，表现为变色和降解产物量增加。然而，MTDSC曲线和FTIR光谱未显示出由奥美拉唑降解产物产生的额外峰。这些方法似乎不够灵敏，无法从分解产物的信号中解析分离出药物和聚合物信号。使用HPLC可以对降解产物进行充分定量。HP-55导致的奥美拉唑降解程度最高，其次是虫胶、HPMCAS-HF和尤特奇L 100。在所应用的储存条件下，未发现与酸性聚合物产生的微环境pH值相关。药物在HP-55和虫胶存在下分解更明显的可能原因被认为是熔融过程和酸性杂质的溶解。
