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

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

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^®.

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.

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