Effect of Surfactants, Gastric Emptying, and Dosage Form on Supersaturation of Dipyridamole in an in Vitro Model Simulating the Stomach and Duodenum

• DOI: 10.1021/mp500196f
• Publication Date: 2014-07-15T19:42:23Z
• Authors: A. Mitra; H. M. Fadda
• Keywords: Supersaturation; Dipyridamole

The purpose of this study was to investigate the influence gastric emptying patterns, surfactants, and dosage form on supersaturation a poorly soluble weakly basic drug, dipyridamole, using an in vitro model mimicking dynamic environment upper gastrointestinal tract, and, furthermore, evaluate usefulness establishing correlations vivo bioavailability for drugs with solubility/dissolution limited absorption. A simulated stomach duodenum comprising four compartments used assess precipitation kinetics as function time. It integrates physiologically relevant fluid volumes, transfer rates, pH changes GI tract. Monoexponential patterns simulating fasted state were compared linear fed state. effect different surfactants commonly oral preparations, specifically, sodium lauryl sulfate (SLS), poloxamer-188, polysorbate-80, dipyridamole investigated while maintaining surface tension fluids at physiological levels without obtaining artificial micellar solubilization drug. behavior dose strengths explored. Significant observed duodenal compartment under all conditions Dipyridamole ratios up 11-fold have been observed, has maintained 120 min. Lower concentrations mononexponential emptying. mean area concentration-time curves (AUC60min) concentration profile is significantly explored (P < 0.05). Our investigations comparison (solution versus suspension) revealed that crystal growth, rather than nucleation, rate-limiting step dipyridamole. dose-response relationship found (AUC∞) range 25 mg 100 (R(2) = 0.886). This agreement pharmacokinetic data reported literature. can provide reliable discriminative screening tool exploring variables or formulations supersaturation/precipitation solubility amount drug solution SSD correlates which absorption undergoes supersaturation/precipitation.