Introduction
The current immediate-release (IR) tablet formulation for epilepsy1 , available in Europe, requires multiple doses due to the drug’s short half-life, making it inconvenient for patients. This case study explores the development of an extended-release (ER) formulation by Syngene’s Formulation Development team for an anti-epileptic drug, aimed at reducing the need for frequent dosing and helping patients suffering from epilepsy.
Challenges for improving patient compliance
The formulation scientists used existing data from the IR product and added new studies to prove the safety and efficacy of the ER formulation. A significant challenge was to develop an ER profile for a highly soluble and permeable molecule (BCS class I)2 using different ratios of sustained-release polymers. The selection of an appropriate pharmacokinetic model added to the complexity.
The team developed an extended-release tablet formulation with a targeted drug release profile of up to 24 hours. This was achieved by pragmatically combining appropriate polymers in the composition and utilizing a simple, conventional manufacturing process such as the dry granulation approach.
Achieved Outcome
The formulation developed at Syngene demonstrated promising pharmacokinetic parameters and the modified release (MR) formulation was bioequivalent to the marketed IR product. This was also tested in different animal models. Following these successful preclinical evaluations, a human bioequivalence study was initiated to further validate the formulation’s efficacy and safety.
The MR formulation developed at Syngene enhances patient convenience and improves compliance by reducing the dosing frequency for epilepsy patients.