A model for drug release from fast phase inverting injectable solutions
A model for drug release from fast phase inverting injectable solutions
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DOI：
10.1016/j.jconrel.2004.09.022
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发表时间：
2005-01-20
影响因子：
10.8
通讯作者：
McHugh, AJ
中科院分区：
文献类型：
--
作者：
Raman, C;McHugh, AJ
A model is developed to describe protein release kinetics from injectable, polymer solution depots which undergo rapid phase inversion on injection. The model consists of a polymer-rich phase and a solvent-rich phase, consistent with experimentally observed phase inversion morphology. Equations in the polymer-rich phase are based on diffusion-reaction mass balances for solvent, water and dissolved drug, and the rate of dissolution of dispersed drug particles. Equations in the water-rich phase are also of the diffusion-reaction type. Transport parameters in the polymer-rich phase are coupled to the ternary thermodynamics through friction formalism, and remaining parameters are estimated from literature data, leaving two free parameters: volume fraction of water-rich phase (epsilon) and k, the mass-transfer coefficient for bath-side transfer of the protein. Variations of these parameters lead to predictions of release profiles that vary from a rapid, burst-like behavior followed by a locking-in of the polymer-rich phase, to a uniform, zero-order profile. Comparisons are made to lysozyme release data for three systems: PLGA solutions in N-methlypyrollidinone (NMP), PLA solutions in NMP, and the latter with added Pluronic. Good agreement between model predictions and data is shown; in particular, the transition from rapid release to zero-order kinetics that occurs on addition of Pluronic is illustrated. (C) 2004 Elsevier B.V. All rights reserved.
