In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations

Area of Science:

• Pharmacology
• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Extended-release dosage forms aim to provide sustained drug levels.
• Understanding the in vitro-in vivo correlation is crucial for dosage form development.
• Cilostazol is used for intermittent claudication.

Purpose of the Study:

• To correlate in vitro drug release with in vivo pharmacokinetics of two extended-release Cilostazol formulations.
• To compare the performance of Pletaal® SR 200 mg capsules and Cilostan® CR 200 mg tablets.
• To evaluate the impact of fed versus fasted states on Cilostazol pharmacokinetics.

Main Methods:

• In vitro drug release studies using USP paddle and basket apparatus in simulated gastric media.
• In vivo pharmacokinetic evaluation in beagle dogs using a single-dose, two-period crossover design.
• Analysis of plasma concentrations, Cmax, AUC0-t, and AUC0-inf under fed and fasted conditions.

Main Results:

• Pletaal® SR 200 mg capsules exhibited significantly higher in vitro drug release rates than Cilostan® CR 200 mg tablets.
• In vivo studies revealed higher Cilostazol plasma concentrations and AUC values in the fed state compared to the fasted state.
• Pletaal® SR 200 mg capsules demonstrated 2.53-fold higher Cmax, 2.89-fold higher AUC0-t, and 2.87-fold higher AUC0-inf compared to Cilostan® CR 200 mg tablets.

Conclusions:

• Pletaal® SR 200 mg capsules demonstrate superior in vitro release characteristics and in vivo pharmacokinetic performance compared to Cilostan® CR 200 mg tablets.
• The fed state enhances Cilostazol absorption, impacting its pharmacokinetic profile.
• The in vitro-in vivo correlation supports the enhanced therapeutic potential of Pletaal® SR 200 mg capsules.