Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing...

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Neuroscience

Background:

• Sobrerol, an oral mucolytic agent, shows therapeutic promise for multiple sclerosis (MS).
• Current dosing regimens (1459 mg/day) require thrice-daily administration, leading to poor patient compliance.
• Developing a modified-release dosage form is crucial for improving sobrerol's MS treatment efficacy and compliance.

Purpose of the Study:

• To develop and characterize oral sustained-release sobrerol pellets.
• To establish a predictive pharmacokinetic model for the target drug product using modeling and simulation.
• To evaluate the potential for improved dosing frequency and reduced daily dose.

Main Methods:

• Development and manufacturing condition evaluation of sobrerol sustained-release pellets.
• In vitro-in vivo correlation (IVIVC) establishment using time-scaling.
• Pharmacokinetic/pharmacodynamic (PK/PD) parameter modeling, including absorption lag time and minimum effective concentration.

Main Results:

• Successfully developed sustained-release sobrerol pellets with evaluated drug release kinetics.
• Established a predictive pharmacokinetic model with key parameters like absorption lag time (0.18 h) and IVIVC (t_vitro = 0.494 t_vivo - 0.0904).
• Predicted a 33.3% reduction in administration frequency (thrice to twice daily) and a 22.8% reduction in daily dose.

Conclusions:

• The developed sustained-release sobrerol formulation significantly improves administration compliance.
• This approach enables rapid development of modified-release dosage forms for sobrerol.
• Enhanced compliance and therapeutic efficacy are achievable with the novel sustained-release formulation for MS treatment.