口服药物的体外吸收模型.ppt

Permeability of NCE in the Presence of Permeation Enhancer Effects of Enhancer on the Membrane Integrity of Caco-2 Cell Monolayers Effects of Enhancer on the Membrane Integrity of Caco-2 Cell Monolayers Conclusion: Effective Level of Permeation Enhancer is about 0.2 % in the Formulation Case Study III Evaluation of three formulations containing NCE B using Continuous Dissolution/Caco-2 System Introduction During the formulation development, it was observed that formulation X composed of new chemical entity A (NCE A) and NCE B had faster onset of action than formulation Y and Z composed of NCEA and NCE B. The objective of this study was to investigate the mechanism for fast onset of action of an orally administered tablet formulation X composed of NCE A and NCE B using Continuous Dissolution/Caco-2 Transport System. Continuous Dissolution/Caco-2 Transport System Dissolution vessel Peristaltic pump Diffusion chambers Caco-2 cell monolayer Ref.: M.J. Ginski, R. Taneja, and J. E. Polli (1999) Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system AAPS PharmSci 1(2) FaSSIF buffer Development of Mathematical Model Simplified Noyes-Whitney Eq: dC/dt = K ? Cs (1) Modified Fick’s First Law: dM/dt = Papp ? A ? Ct (2) Integrate (1) and (2) to yield: Mt= ? ? Papp ? A ? K ? Cs ? t2 Where Mt is the accumulative amount of drug in the receiver side of the side-by-side diffusion cell. Mt integrates the contributions of dissolution and permeation processes into overall drug absorption kinetics. Dissolution of NCE A from Formulation X, Y, Z in FaSSIF Buffer ?: Formulation X; ■: Formulation Y; ▲: Formulation Z Absorption of NCE A in Dissolution/Caco-2 System ?: Formulation X; ■: Formulation Y; ▲: Formulation Z Evaluation of Mathematical Model Using the Experimental Data ?: Formulation X; ■: Formulation Y; ▲: Formulation Z Dissolution of NCE B from Three Tablet Formulations in FaSSIF Buffer ?: Formulation