Development, Characterization, and in-vivo Pharmacokinetic Study of Lamotrigine Solid Self-Nanoemulsifying Drug Delivery System

Abstract

Purpose

This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrigine (LMG) for enhancing its dissolution and oral bioavailability (BA).

Methods

Nineteen liquid SNEDDS were prepared (R1-R19) using D-optimal design with different ratios of oil, surfactant (S), and cosurfactant (Cos). The formulations were characterized regarding robustness to dilution, droplet size, thermodynamic stability testing, self-emulsification time, in-vitro release in 0.1 N HCl and phosphate buffer (PB; pH 6.8). Design Expert^® 11 software was used to select the optimum formulations. Eight S-SNEDDS were prepared (S1-S8) using 2³ factorial design, and characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimum formulation was chosen regarding in-vitro drug released in 0.1 N HCl and PB, compared to pure LMG and commercial tablet (Lamictal^®). The BA of LMG from the optimized S-SNEDDS formulation was evaluated in rabbits compared to pure LMG and Lamictal^®.

Results

The optimized S-SNEDDS was S2, consisting of R9 adsorbed on Aeroperl^® 300 in a ratio of 1:1, with the best results regarding in-vitro drug released in 0.1 N HCl at 15 min (100%) compared to pure LMG (73.40%) and Lamictal^® (79.43%), and in-vitro drug released in PB at 45 min (100%) compared to pure LMG (30.46%) and Lamictal^® (92.08%). DSC, PXRD, and SEM indicated that LMG was molecularly dispersed within the solid nano-system. The BA of S2 was increased 2.03 and 1.605 folds compared to pure LMG, and Lamictal^®, respectively.

Conclusion

S2 is a promising S-SNEDDS formulation. It can be a potential carrier for improving dissolution, and BA of LMG.

Keywords:

• antiepileptic drug
• lipid-based formulation
• porous carriers
• Aeroperl^® 300
• oral bioavailability

Acknowledgments

The authors are so grateful to the support staff of Pharmaceutics Department, Faculty of Pharmacy in Health Sciences Center, Kuwait University and Misr University for Science and Technology for their indispensable technical support during conducting the practical work of this research.

Disclosure

The authors report no conflicts of interest in this work.