title: Improvement of physicochemical properties of an antiepileptic drug by salt engineering.
abstract: The focus of the present investigation was to evaluate the feasibility of using cyclamic salt of lamotrigine in order to improve its solubility and intrinsic dissolution rate (IDR). The salt was prepared by solution crystallization method and characterized chemically by fourier transform infrared spectroscopy (FTIR), proton ((1)H) and carbon ((13)C) nuclear magnetic resonance (liquid and solid, NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), physicochemically for solubility, IDR, solution and solid-state stability, and polymorphism by solution recrystallization and slurry conversion studies. The FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt formation. The salt formation increased lamotrigine solubility by 19-fold and IDR by 4.9-fold in water. The solution and solid-state stability were similar to parent molecule and were resistant to polymorphic transformation. In conclusion, cyclamic salt of lamotrigine provides another potential avenue for the pharmaceutical development of lamotrigine with improved physicochemical properties especially for pediatric population. It is also possible that appropriate dosage forms can be formulated with much lower drug amount and better safety profile than existing products.
authors.affiliation: Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, White Oak, LS Building 64, Room 1070, 10903 New Hampshire Ave., Silver Spring, Maryland 20993-002, USA.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Zidan
authors.forename: Raghu
authors.initials: R
authors.lastname: Samy
authors.forename: Vilayat A
authors.initials: VA
authors.lastname: Sayeed
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis*; D002616:Chemical Engineering / Q000379:methods*; D055598:Chemical Phenomena; D003494:Cyclamates / Q000138:chemical synthesis*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000927:Anticonvulsants; D003494:Cyclamates