A Simulated Stomach Duodenum Model Predicting the Effect of Fluid Volume and Prandial Gastric Flow Patterns on Nifedipine Pharmacokinetics From Cosolvent-Based Capsules

Abstract

Nifedipine is a Biopharmaceutics Classification System class II drug displaying large variability in absorption even when administered as immediate-release soft gelatin capsules of a cosolvent formulation. This in vitro study sought to understand the reasons behind variability in nifedipine absorption, how it can be minimized, and if it can be predicted using in vitro models. A dynamic in vitro simulated stomach duodenum model was used to explore drug concentration-time profiles of nifedipine soft gelatin capsules under conditions simulating how patients take their medicines. Specifically, the effect of prandial gastric emptying patterns and fluid volume administration (250 mL vs. 50 mL water) were investigated. Significant supersaturation of nifedipine was observed. While administration of large and small water volumes gave rise to a similar C and area under the curve (AUC), the coefficient of variation in AUC was 4.8% and 49%, respectively, which can be attributed to differences in precipitation kinetics. Fasting and fed gastric emptying patterns also gave rise to a similar AUC; however, C was significantly lower in the fed state. These trends are consistent with previously published in vivo results in healthy volunteers. The simulated stomach duodenum provides a good discriminative screening tool for predicting trends in drug concentration profiles of Biopharmaceutics Classification System class II drugs.

Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system

“…Different multicompartment models are used to simulate the passage of dosage forms/drugs along the GI tract (31). Some models focus primarily on changes in the gastric volumes after co-administration of formulation with water (32)(33)(34)(35)(36). To increase physiological relevance, some in vitro models also simulate the gastric motility patterns during MMC cycles (37)(38)(39)(40).…”

Interactions between Food and Drugs, and Nutritional Status in Renal Patients: A Narrative Review

“…Fluid intake can affect the absorption of a drug. Indeed, the volume and the temperature of beverages may alter the transit of the drug through the stomach, so modifying the time necessary for the appearance of the pharmacological effect [ 60 ]. With the exception of water, the intake of any beverage in conjunction with the drug could lead to a different absorption of the latter.…”