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 h. 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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