Development of Capsules Filled with Phenytoin and Berberine Loaded Nanoparticles- A New Approach to Improve Anticonvulsant Efficacy

Abstract:

Introduction: Currently used anticonvulsant drugs are not totally effective to control seizures. Phenytoin is a classic instance where its efficiency is inhibited through high metabolization (90%-95%) and back transport through cytochrome P450 and P-glycoprotein, respectively. To explore and attain improved anticonvulsant efficacy combination therapy with nanotechnology has been adopted in this research. Objective: development of nanotechnology-based drug delivery system by filling berberine and phenytoin nanoparticles in capsules. Method: phenytoin and berberine nanoparticles were formulated individually by utilising a solvent evaporation technique and later the mixture is filled in the hard gelatine capsule to create a single-unit dosage. Results: The formulated nanoparticles were evaluated in terms of FTIR and DSC studies, mean particle diameter and zeta-potential, entrapment efficiency and in vitro release. FTIR and DSC studies had proved that formulation components are compatible. SEM report revealed that all the nanoparticles were smooth, spherical in shape and within the size range of 100-500nm. Zeta-potential of phenytoin and berberine nanoparticles was negative (-2.61 and -35.9mV, respectively). In vitro release kinetics was in the accordance with the Higuchi model. The improved efficacy was proved by MES and Histopathological studies. Conclusion: The successfully developed Capsules filled with the Nanoparticles (Combination therapy) exhibited improved efficacy than that of single phenytoin therapy.

Key words: Status epilepticus (SE), Phenytoin, Berberine, Nanoparticles, Cytochrome P-450, P-Gp efflux transporters.