OPTIMIZING LEVETIRACETAM SURFACTANT-BASED NANOVESICLES (LEV-NVS) GEL FOR TREATING EPILEPSY USING EXPERIMENTAL DESIGN

MAHMOUD H. TEAIMA; HUSSIEN MOHAMED AHMED EL-MESSIRY; HAJAR ABDULRADI SHAKER; MOHAMED A. EL-NABARAWI; DOAA A. HELAL

doi:10.22159/ijap.2023v15i2.46450

Authors

MAHMOUD H. TEAIMA Department of Pharmaceutics and industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt https://orcid.org/0000-0002-7565-301X
HUSSIEN MOHAMED AHMED EL-MESSIRY Pharmaceutics Department, Egyptian Drug Authority, Cairo, Egypt https://orcid.org/0000-0002-3517-2027
HAJAR ABDULRADI SHAKER Pharmaceutics Department, Egyptian Drug Authority, Cairo, Egypt
MOHAMED A. EL-NABARAWI Department of Pharmaceutics and industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
DOAA A. HELAL Department of Pharmaceutics, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt https://orcid.org/0000-0002-1222-8112

DOI:

https://doi.org/10.22159/ijap.2023v15i2.46450

Keywords:

intranasal, Levetiracetam, nanovesicles, brain-targeted, antiepileptic, solvent evaporation technique

Abstract

Objective: To develop and estimate the intranasal delivery of Levetiracetam surfactant-based nanovesicles (Lev-Nvs) as a brain-targeted antiepileptic delivery system prepared via solvent evaporation technique.

Methods: Optimized formulation F (OPT) chosen by the Design-Expert® program gave the highest entrapment efficiency (EE%) was incorporated into the gel. An experimental design was adopted utilizing various (span 65) surfactants and different cholesterol ratios.The (Lev-Nvs) nanovesicles were formulated by solvent evaporation technique and evaluated for in-vitro characterization parameters such as zeta sizer,Transmission Electron Microscopy (TEM), zeta potential .The nasal gel was evaluated for drug-excipient interactions utilizing Fourier Transform Infrared Spectroscopy (FTIR) and subjected to in-vitro and in-vivo release studies,

Results: The results indicated that the entrapment efficiency (EE%) of Levetiracetam surfactant-based nano-vesicles (Lev-Nvs) could be modulated by the alterations in surfactant and cholesterol concentrations. Optimized formulation F (OPT) showed an entrapment efficiency of (87.9 ± 1.06 %), (206.7 ± 20.43 nm) particle size, (-34.1) zeta potential and (0.979) PDI. The nanovesicle nasal gels of the F(OPT) were prepared using Carbopol 940 at different concentrations. G 0.375 formulation showed the best in vitro drug release (87.36%) after 12 hrs. Finally, the comparative in vivo pharmaco-kinetics release studies on rats revealed considerable, sustained release of the nanovesicle nasal gel and higher relative bioavailability than an equivalent dose of oral solution (293.85%).

Conclusion: Our study proves the improved efficacy of Levetiracetam as a surfactant-based nanovesicle intranasal gel in the brain targeting antiepileptic medication.

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