Drug Design, Development and Therapy (Oct 2020)
Development, Characterization, and in-vivo Pharmacokinetic Study of Lamotrigine Solid Self-Nanoemulsifying Drug Delivery System
Abstract
Rehab Abdelmonem,1 Marian Sobhy Azer,2 Amna Makky,3 Abdelazim Zaghloul,4 Mohamed El-Nabarawi,3 Aly Nada4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October City, Giza, Egypt; 2Department of Pharmaceutics, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October City, Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Kuwait City, KuwaitCorrespondence: Marian Sobhy AzerDepartment of Pharmaceutics, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October City, Giza, EgyptTel +2 010 050 529 83Email [email protected] El-NabarawiDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptTel +2 010 014 244 39Email [email protected]: 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
