title: Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization.
abstract: The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals.
authors.affiliation: College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Cao
authors.affiliation: College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
authors.affiliation: College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Nair
authors.initials: N
authors.lastname: Rodriguez-Hornedo
authors.affiliation: College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Amidon
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D033362:Powder Diffraction; D012439:Saccharin / Q000737:chemistry*; D020156:Salicylic Acid / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D008823:Micelles; D002220:Carbamazepine; D012439:Saccharin; D020156:Salicylic Acid
keywords: cocrystal dissolution modeling; diffusions; flux predictions; interfacial pH; mass transport analysis; micellar solubilization