DISSOLUTION OF THEOPHYLLINE MONOHYDRATE AND ANHYDROUS THEOPHYLLINE IN BUFFER SOLUTIONS
DISSOLUTION OF THEOPHYLLINE MONOHYDRATE AND ANHYDROUS THEOPHYLLINE IN BUFFER SOLUTIONS
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DOI：
10.1002/jps.2600750515
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发表时间：
1986-05-01
影响因子：
3.8
通讯作者：
CROMMELIN, DJA
中科院分区：
文献类型：
--
作者：
DESMIDT, JH;FOKKENS, JG;CROMMELIN, DJA
The dissolution kinetics of theophylline monohydrate and anhydrous theophylline were investigated with a rotating-disk apparatus in buffer solutions at 298 K under sink conditions. The observed dissolution rate of theophylline monohydrate under various conditions agreed well with predictions based on the Extended Simultaneous Chemical Reaction and Dissolution concept. Below 337 K, anhydrous theophylline is converted to theophylline monohydrate in contact with water. The dissolution profile of anhydrous theophylline can be divided into three phases: (a) a pre-transformation phase: anhydrous theophylline dissolves; (b) the transformation phase, during which its dissolution rate drops to the level of the theophylline monohydrate dissolution rate; and (c) steady state, at which the dissolution rate of anhydrous theophylline equals the dissolution rate of theophylline monohydrate. The presence of theophylline monohydrate crystals at the dissolving surface was confirmed by IR spectroscopy and microscopic observation. The length of the transformation phase, depending on the characteristics of the diffusion boundary layer, varied with the experimental conditions (e.g., pH and rotation speed). It was concluded that during the dissolution process the disk is covered with theophylline monohydrate crystals that precipitate from the supersaturated medium adjacent to the disk surface, and that crystallization of theophylline monohydrate is a precipitation process controlled by hydrodynamic and diffusion parameters.
