Solis-Cruz Bruno, Hernandez-Patlan Daniel, Morales Hipólito Elvia A, Tellez-Isaias Guillermo, Alcántara Pineda Alejandro, López-Arellano Raquel
Laboratory 5: LEDEFAR, Multidisciplinary Research Unit, Superior Studies Faculty at Cuautitlan (FESC), National Autonomous University of Mexico (UNAM), Cuautitlan Izcalli 54714, Mexico.
Nanotechnology Engineering Division, Polytechnic University of the Valley of Mexico, Tultitlan 54910, Mexico.
Pharmaceutics. 2023 Aug 24;15(9):2191. doi: 10.3390/pharmaceutics15092191.
The use of the USP IV apparatus (flow-through cell) has gained acceptance in recent years due to its versatility and ability to discriminate due to its hydrodynamic conditions. Therefore, the objective of the present study was to develop a discriminative dissolution method in the USP IV apparatus using the open-loop configuration, as well as to propose a method to compare non-cumulative dissolution profiles obtained in the open-loop configuration considering kinetic parameters and validate its predictive power through its comparison with independent and dependent methods using five commercial immediate-release tablet drugs (one reference drug and four generic drugs) of metoprolol tartrate as a model drug. The comparison of the non-accumulated dissolution profiles consisted of determining the geometric ratio of C, AUC, AUC and T (kinetic parameters) of the generic/reference drugs, whereby generic drugs "C" and "D" presented the highest probability of similarity since their 90% confidence intervals were included, or they were very close to the acceptance interval (80.00-125.00%). These results were consistent with the , bootstrap and dissolution efficiency approaches (independent models). In conclusion, the proposed comparison method can be an important tool to establish similarity in dissolution profiles and to facilitate the development/selection of new formulations and positively ensure bioequivalence in clinical studies.
近年来，由于美国药典IV装置（流通池）具有多功能性以及因其流体动力学条件而具备区分能力，它已获得认可。因此，本研究的目的是开发一种使用开环配置的美国药典IV装置中的区分性溶出方法，以及提出一种方法，通过考虑动力学参数来比较在开环配置中获得的非累积溶出曲线，并通过与使用五种市售速释片剂药物（一种参比药物和四种仿制药物）酒石酸美托洛尔作为模型药物的独立和相关方法进行比较，来验证其预测能力。非累积溶出曲线的比较包括确定仿制/参比药物的C、AUC、AUC和T（动力学参数）的几何比值，由此仿制药物“C”和“D”呈现出最高的相似概率，因为它们的90%置信区间被包含在内，或者它们非常接近接受区间（80.00 - 125.00%）。这些结果与自助法和溶出效率方法（独立模型）一致。总之，所提出的比较方法可以成为建立溶出曲线相似性以及促进新制剂开发/选择并在临床研究中积极确保生物等效性的重要工具。
