The Effect of Spinach on the dissolution of Clopidogrel tablets

Abstract

Abstract Background: Drug-food interaction is a serious issue that should be taken into consideration when administering drugs for chronic diseases and life-saving drugs such as anticoagulants. Alteration of the properties of gastric fluid such as pH and film precipitation on tablet had a significant impact on dissolution and release of the drug which may further affect its therapeutic effect. Methods: In vitro disintegration and dissolution tests were done in HCl buffer and phosphate buffer with and without spinach extract in each media. High performance liquid chromatography (HPLC) analysis was performed to measure the drug release in all media. Disintegration was performed in simulated intestinal fluid and compared to disintegration of drug in 5% spinach without removal of leaves to study the effect of film precipitation on the penetration of fluid onto the tablet. Results: Dissolution was reduced at increased concentrations of spinach extract. It was found that, an increased pH in HCl buffer whenever spinach extract concentration increased, as well as the reduced solubility of clopidogrel in the relatively high pH phosphate buffer, or it can be attributed to the possibility of formation of a new complex between metals in spinach extract and clopidogrel drug. Addition of spinach leaves to media resulted in reduced penetration of fluid onto the tablet and delayed disintegration was observed. In-vitro In-vivo correlation (IVIVC) was observed in HCl buffer with a value of R2 0.74. Conclusion: Concomitant administration of spinach soup with clopidogrel tablets causes decreased plasma concentration of active pharmaceutical ingredient (API) which may lead to decreased therapeutic efficacy and increased risk of cardiovascular events.