Thermodynamic and Crystallization of Lamotrigine Cocrystal

Abstract

Two novel lamotrigine cocrystals, namely, lamotrigine (LAM) phthalimide (PTL) cocrystal (1) and lamotrigine (LAM) succinimide (SUC) cocrystal monohydrate (1:1:1) (2), were successfully synthesized by liquid-assisted grinding and evaporative crystallization, and their structures were determined by XRD (power and single-crystal X-ray diffraction) and FT-IR. Ternary phase diagrams of LAM–PTL were constructed for the obtained cocrystal in isobutanol and ethyl propionate at two different temperatures, i.e., 298.15and 303.15 K. A narrow stability region was found for the pure LAM–PTL cocrystal in the phase diagram at both temperatures. The solubility of LAM–PTL was measured by suspending cocrystal in solutions of varying PTL concentrations in ethyl propionate and isobutanol. The mathematical model described by the solubility product of cocrystal components K sp and by solution complexation constants K 11 was used to fit the solubility of LAM–PTL cocrystal. It can be concluded that K sp values increase as the cocrystal solubility increases, while K 11 values decrease. Graphical representation of the cocrystal solubility dependence on ligand concentration will serve as a diagnostic tool for the stoichiometry of solution complexes. The results of the stability study demonstrated that 1 and 2 are stable under the conditions of both 85% and 98% RH at 25 °C.

Levofloxacin Cocrystal/Salt with Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve Antimicrobial Efficiency

“…The diffraction peaks of CFA observed at 2-theta (deg) and PDA peaks were noted. The diffraction peaks of starting material LEV [ 13 , 15 ], PTH [ 27 ] and CFA [ 51 , 76 ] show good consistency with previously compiled values. New diffraction peaks appeared at 11.50°, 20°, 29.699° and 44.2° while LEV peaks (6.29° and 26.36°) and some of the PTH peaks disappeared in the diffractogram of LEV-PTH cocrystal.…”

“…Therefore, the active interaction sites of PTH and CFA have also the possibility to interact with N of methylpiprizine ring to form supramolecular synthons. Furthermore, in lamotrigine-PTH cocrystals the amide part of PTH interacts with the aminopyridine of lamotrigine [ 27 ] while transfers of protons from the carboxylic group of CFA to the tertiary amino group of venlafaxine have taken place in venlafaxine-CFA salt [ 51 ].…”

“…Phthalimide (PTH) is usually employed in the design of potential anti-tumor [ 22 ], immunemodulatory [ 23 ], anti-angiogenic [ 24 ], anti-microbial [ 25 ] and anti-inflammatory [ 26 ] drugs. The Lamotrigine-PTH and venlafaxine-CFA cocrystal/salt have also been reported in literature which showed better performance than respective pure drug [ 27 ].…”

Crystal products of lamotrigine-citric acid for improvement of in vitro drug release in simulated gastric fluid

“…For quicker onset of action lamotrigine orally disintegrating tablet has been formulated by Patil et al 9 Though, several crystal products of LT has been reported over past years for the improvement of solubility and dissolution rate, however an optimized crystalline product of LT with citric acid (CA) is yet to be reported. [10][11][12] The present work aimed for the development and characterization of a novel crystalline product of LT with CA to improve its dissolution rate and oral absorption for enhanced clinical outcome. The study involved characterization of the LT-CA crystal products by different analytical techniques along with in vitro dissolution studies to report the optimized crystal product for future in vivo studies.…”

Donepezil Multicomponent Systems: Donepezil–Water–Maleic Acid Crystals and More

“…Pharmaceutical multicomponent systems are typically composed of a main component, an active pharmaceutical ingredient (API), and one or more auxiliary components, and they can have either a solid or liquid state at room temperature . Salts have proven to be the most successful multicomponent system in terms of improving pharmaceutical performance due to their advantageous crystallinity, solubility, stability, and/or bioavailability. − Over the past few decades, however, cocrystals have gained significant attention as an alternative to salts when the API does not contain an ionizable component that allows the formation of a salt or when certain properties that salts do not possess are required. ,− Other interesting multicomponent systems that are on the salt–cocrystal continuum or that consist of a sodium supramolecular complex have also been discovered. , …”