Factors affecting the absorption of nilvadipine from disintegration-controlled matrix tablet in dogs

Area of Science:

• Pharmacokinetics and Drug Delivery
• Gastrointestinal Physiology

Background:

• Disintegration-controlled matrix tablets (DCMT) offer potential for modified drug release.
• Understanding the pharmacokinetic profile of nilvadipine (NiD) from DCMT is crucial for optimizing therapeutic efficacy.

Purpose of the Study:

• To investigate the pharmacokinetics of nilvadipine (NiD) from disintegration-controlled matrix tablets (DCMT).
• To identify biological factors influencing NiD absorption from DCMT, including food effects and gastro-intestinal transit time.

Main Methods:

• Preparation and in vitro dissolution testing of two DCMT formulations (DCMT-M, DCMT-S) and immediate-release (IR) tablets.
• Pharmacokinetic analysis in fasted and fed dogs, measuring Tmax, mean residence time, and AUC (0-infinity).
• In vivo absorption profiling using deconvolution and regional absorption studies with NiD solution.

Main Results:

• DCMT formulations exhibited longer Tmax and mean residence time compared to IR tablets.
• NiD absorption from DCMT-M was unaffected by food, showing comparable AUC to IR tablets.
• NiD absorption from DCMT-S was reduced in fasted dogs but improved when fed, indicating prolonged GI transit enhanced release and absorption.

Conclusions:

• Gastro-intestinal transit time is the primary determinant of drug release and absorption from DCMT.
• Drug permeation is not a limiting factor for NiD absorption, as it is well-absorbed throughout the canine jejunum, ileum, and colon.
• DCMT performance is significantly influenced by the duration of gastro-intestinal transit, impacting nilvadipine bioavailability.