DEVELOPMENT OF GABAPENTIN-LOADED SOLID LIPID NANOPARTICLE FOR ALLEVIATING SEIZURE ACTIVITY IN PICROTOXIN AND BICUCULLINE-INDUCED RATS

POOJA AGARWAL; VASUDHA BAKSHI

doi:10.22159/ijap.2024v16i6.51157

Authors

POOJA AGARWAL School of Pharmacy, Anurag University, Venkatapur, Ghatkesar, Medchal-Malkajgiri, Hyderabad, Telangana, India https://orcid.org/0009-0009-9984-4871
VASUDHA BAKSHI School of Pharmacy, Anurag University, Venkatapur, Ghatkesar, Medchal-Malkajgiri, Hyderabad, Telangana, India https://orcid.org/0000-0002-0819-2532

DOI:

https://doi.org/10.22159/ijap.2024v16i6.51157

Keywords:

Gabapentin, Box-behnken design, Solid lipid nanoparticle, Glyceryl tripalmitate, Poloxamer-188, In vitro release, In vivo anti-convulsion study

Abstract

Objective: The current research aimed to prepare gabapentin-loaded Solid Lipid Nanoparticles (SLN) for alleviating seizure activity in picrotoxin and bicuculline-induced Wistar rats.

Methods: Gabapentin-loaded SLNs were formulated using a Box-Behnken experimental design with three-level three-factor consisting of 17 experimental runs by micro-emulsification. Three independent parameters were considered in this study, namely sodium glyceryl tripalmitate (A), RPM (B), and Poloxamer-188 (C). Particle size, drug release, and Encapsulation Efficiency (EE) as dependent variables. The formulation was evaluated for drug release, EE, Attenuated Total Reflection (ATR), Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), surface morphology, particle size, zeta potential, in vivo anti-convulsion study.

Results: The data collected during the experiment includes the measurements of EE (Encapsulation Efficiency), drug release at the 12^th h, and particle size. It was reported that formulations containing a high concentration of Glyceryl tripalmitate (50%) had a high Encapsulation Efficiency (EE). The in vitro release results indicate that F17 demonstrated a maximum drug concentration of 99.99% within a 12 h. The optimization process was conducted using mathematical and graphical methods. From ATR spectra, it was found that there are no such major interactions between gabapentin and excipients. A significant endothermal peak was seen in the DSC investigation at 208.81 °C. X-ray diffraction revealed that gabapentin was present in the crystalline form. Drug crystals and SLN were seen to be dispersed and scattered from Scanning Electron Microscope (SEM). The optimized formulation's particle size was found to be 203.4 nm, the Polydispersity Index (PI) of 0.426, and the zeta value of 16.5 mV; indicating stability. Following a lethal and chronic dosage of picrotoxin, the gabapentin-SLN exhibited a higher anticonvulsant efficacy, according to in vivo research on rats (p<0.05).

Conclusion: Compared to the Bicuculline model, the optimized SLN demonstrated superior outcomes regarding seizure initiation in the Picrotoxin-induced convulsion.

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