Two-Stage Single-Compartment Models to Evaluate Dissolution in the Lower Intestine

Area of Science:

• Pharmacokinetics and Drug Delivery
• Gastrointestinal Physiology

Background:

• Accurate evaluation of drug dissolution in the lower gastrointestinal tract is crucial for predicting in vivo performance.
• Existing models may not fully capture the complex physiological conditions of the distal ileum and ascending colon.

Purpose of the Study:

• To propose and evaluate two-stage single-compartment models for assessing drug dissolution characteristics in the distal ileum and ascending colon.
• To simulate conditions relevant to bioavailability and bioequivalence studies in both fasted and fed states.

Main Methods:

• Utilized mini-paddle and compendial flow-through apparatus in a closed-loop mode.
• Employed immediate-release products of sulfasalazine and L-870,810, and a mesalamine colon-targeting product.
• Simulated regional differences by changing medium composition to mimic distal ileum (SIFileum) and ascending colon environments.

Main Results:

• Dissolution in the lower intestine differs significantly from the upper intestine, influenced by regional pH, fluid convection, and luminal components.
• The colon-targeting product Asacol® (400 mg/tab) demonstrated sensitivity to the type and intensity of fluid convection.
• Model data aligned with available human pharmacokinetic data across all tested products.

Conclusions:

• Two-stage single-compartment models show promise for evaluating drug dissolution in the lower intestine.
• Further research is needed to explore the impact of fluid convection and viscosity on the luminal performance of various APIs and drug products.