Ozturk S S, Palsson B O, Dressman J B
Department of Chemical Engineering, University of Michigan, Ann Arbor 48109.
Pharm Res. 1988 May;5(5):272-82. doi: 10.1023/a:1015970502993.
The dissolution kinetics of ionizable drugs (weak acids or bases) are analyzed with a mathematical model derived from the theory of mass transfer with chemical reaction. The model assumes that the overall process is diffusion limited, that all the reactions are reversible and instantaneous, and that dissolution and reaction are limited to the stagnant fluid film adjacent to the solid phase. Dissolution into buffered and unbuffered aqueous solutions are considered separately, with convenient analytical solutions obtained in both cases. In addition, equations for the time to partial and complete dissolution are derived. The dissolution rate is shown to be dependent on the pKa and intrinsic solubility and the medium properties, i.e., pH, buffer capacity, and mass transfer coefficient. Equations of a form analogous to the nonionized case are derived to account explicitly for all these factors, with dissolution rates expressed in terms of the product of a driving force (concentration difference) and resistance (inverse of mass transfer coefficient). The solutions are in an accessible analytical form to calculate the surface pH and subsequently the surface concentrations driving the drug dissolution. Numerical examples to illustrate dissolution into unbuffered and buffered media are presented and the results are shown to be in accord with experimental data taken from the literature.
利用基于伴有化学反应的传质理论推导的数学模型，对可电离药物（弱酸或弱碱）的溶解动力学进行了分析。该模型假定整个过程受扩散限制，所有反应均为可逆且瞬时的，并且溶解和反应仅限于与固相相邻的停滞液膜。分别考虑了药物在缓冲水溶液和非缓冲水溶液中的溶解情况，两种情况下均获得了简便的解析解。此外，还推导了部分溶解和完全溶解时间的方程。结果表明，溶解速率取决于药物的pKa、固有溶解度以及介质性质，即pH值、缓冲容量和传质系数。推导了形式类似于非离子化情况的方程，以明确考虑所有这些因素，溶解速率以驱动力（浓度差）与阻力（传质系数的倒数）的乘积表示。这些解采用易于理解的解析形式，用于计算表面pH值以及随后驱动药物溶解的表面浓度。给出了说明药物在非缓冲介质和缓冲介质中溶解情况的数值示例，结果表明与文献中的实验数据一致。
