Multicomponent solids of lamotrigine with some selected coformers and their characterization by thermoanalytical, spectroscopic and X-ray diffraction methods

Abstract

The present study investigates the structural and pharmaceutical properties of different multicomponent crystalline forms of lamotrigine (LTG) with some pharmaceutically acceptable coformers viz. nicotinamide (1), acetamide (2), acetic acid (3), 4-hydroxy-benzoic acid (4) and saccharin (5). The structurally homogeneous phases were characterized in the solid state by DSC/TGA, FT-IR and XRD (powder and single crystal structure analysis) as well as in the solution phase. Forms 1 and 2 were found to be cocrystal hydrate and cocrystal, respectively, while in forms 3, 4 and 5, proton transfer was observed from coformer to drug. The enthalpy of formation of multicomponent crystals from their components was determined from the enthalpy of solution of the cocrystals and the components separately. Higher exothermic values of the enthalpy of formation for molecular complexes 3, 4 and 5 suggest these to be more stable than 1 and 2. The solubility was measured in water as well as in phosphate buffers of varying pH. The salt solvate 3 exhibited the highest solubility of the drug in water as well as in buffers over the pH range 7-3 while the cocrystal hydrate 1 showed the maximum solubility in a buffer of pH 2. A significant lowering of the dosage profile of LTG was observed for 1, 3 and 5 in the animal activity studies on mice.

Improvement of Physicochemical Properties of an Antiepileptic Drug by Salt Engineering

“…It produced acidic microenvironment around the LMT molecule that favored its ionization and thus caused more drugs to dissolve in the media. Similar results were reported about the saccharinate salt of LMT resulted in an insignificant increase in its solubility by the same principle (11,40). Most remarkable improvement in the solubility of LMT was observed in water (0.23±0.01 and 4.36±0.11 mg/ml for LMT and its salt, respectively) whereby it caused 19-fold increase in its solubility.…”

In - situ synchrotron wide-angle X-ray diffraction as a rapid method for cocrystal/salt screening

“…The melting point of the extruded LAM-SAC crystal was 262 C measured by DSC (shown in Fig. S2), slightly different from the reported melting points (Chadha et al, 2011;Galcera and Molins, 2008).…”

“…Various methodologies for cocrystal screening are employed, such as solvent evaporation (Weyna et al, 2009), slurry conversion (Luu et al, 2013;Zhang et al, 2007), grinding technique (Karki et al, 2007;Friš9 ci c et al, 2006;Trask et al, 2006) and thermal methods (Lu et al, 2008;Yamashita et al, 2014;Berry et al, 2008;Chadha et al, 2011;Lekši c et al, 2012). However, solution-based approach is environmentally unfriendly and has the risks of single component crystallization and solvate formation.…”

Solid State Characterization of a Novel Physical Interaction (Paracetamol-Chlorpheniramine Maleate)

“…, not many changes in 2θ occurred but a significant shift of CTM was observed. The shifting of diffractogram has exhibited the interaction of material in solid state or changes of internal space group of molecular structure [20][21]. The result of diffractogram showed shifting for several peaks at 2Ɵ angle, it showed the changes in space group of structural [14].…”