Case Study In silico Pharmacokinetic Modeling to Reformulate Product for Lifecycle Extension

Benefits of Case:

• Lifecycle extension
• Increase confidence in formulation strategy
• Trouble shooting development program
• Decrease number of prototypes to be tested in expensive Phase 1 clinical studies

Background and Challenge:
The Client was exploring avenues for lifecycle extension by reformulating a twice-a-day marketed product into a once-a-day product. The Client approached PharmaDirections, to determine the feasibility and development path for reformulation. All previous attempts by the Sponsor using a trial and error formulation approach to develop the once daily extended release formulation had been unsuccessful.

PharmaDirections Strategy:

• Implement in silico pharmacokinetic analyses
• Two computer aided approaches were used: One based on in vitro-in vivo correlations(IVIVC) with empirical data, while the second approach used physiochemical parameters intrinsic to the molecule to predict pharmacokinetic profiles

The Objectives:

• To predict the desired drug release rates/dissolution profiles for a formulation to achieve the targeted once-daily dosing regimen and pharmacokinetic profile
• Use the predicted product dissolution profiles to design product formulations that would meet the targeted pharmacokinetic profile for clinical studies

Value for the Client:

• Both the IVIVC and physiological approaches suggested the same dosage form drug release rate that should be used to achieve the desired dosing schedule
• Both approaches showed that the previous attempts by the client company at reformulation had been unsuccessful due to their incorrect selection of a drug release rate as a formulation target