Preparation and Solid-State Characterization of Three Novel Multicomponent Solid Forms of Oxcarbazepine: Improvement in Solubility through Saccharin Cocrystal

Oxcarbazepine (OXCBZ) is an antiepileptic drug with low aqueous solubility, and its dissolution is the rate limiting step for absorption. The present work investigates three muticomponent solid forms of OXCBZ with water-soluble coformers with an aim to enhance its solubility and in vivo performance. The experiments based on the solution method yielded two cocrystals, with succinic acid (<b>1</b>) and saccharin (<b>2</b>) and a solvate with acetic acid (<b>3</b>). Compound <b>1</b> was identified by single crystal X-ray diffraction (XRD) as a solvated cocrystal involving eight molecules of OXCBZ, four molecules of succinic acid, and four molecules of chloroform in the unit cell. The structural changes upon desolvation of cocrystal <b>1</b> have also been examined. Single crystals of compounds <b>2</b> and <b>3</b> could not be obtained in a size suitable for single crystal X-ray analysis and thus was studied by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, powder XRD, Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. Furthermore, the powder dissolution of compounds <b>1</b> (desolvated form), <b>2</b>, <b>3</b>, and OXCBZ was performed in an acidic aqueous medium and analyzed by high performance liquid chromatography. Their physical stability was also assessed. The cocrystal with saccharin showed a significant improvement in the solubility of OXCBZ in aqueous conditions and exhibited a lower ED₅₀ value as compared to pure OXCBZ

Preparation and Solid-State Characterization of Three Novel Multicomponent Solid Forms of Oxcarbazepine: Improvement in Solubility through Saccharin Cocrystal

Oxcarbazepine (OXCBZ) is an antiepileptic drug with low aqueous solubility, and its dissolution is the rate limiting step for absorption. The present work investigates three muticomponent solid forms of OXCBZ with water-soluble coformers with an aim to enhance its solubility and in vivo performance. The experiments based on the solution method yielded two cocrystals, with succinic acid (<b>1</b>) and saccharin (<b>2</b>) and a solvate with acetic acid (<b>3</b>). Compound <b>1</b> was identified by single crystal X-ray diffraction (XRD) as a solvated cocrystal involving eight molecules of OXCBZ, four molecules of succinic acid, and four molecules of chloroform in the unit cell. The structural changes upon desolvation of cocrystal <b>1</b> have also been examined. Single crystals of compounds <b>2</b> and <b>3</b> could not be obtained in a size suitable for single crystal X-ray analysis and thus was studied by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, powder XRD, Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. Furthermore, the powder dissolution of compounds <b>1</b> (desolvated form), <b>2</b>, <b>3</b>, and OXCBZ was performed in an acidic aqueous medium and analyzed by high performance liquid chromatography. Their physical stability was also assessed. The cocrystal with saccharin showed a significant improvement in the solubility of OXCBZ in aqueous conditions and exhibited a lower ED₅₀ value as compared to pure OXCBZ

Preparation and Solid-State Characterization of Three Novel Multicomponent Solid Forms of Oxcarbazepine: Improvement in Solubility through Saccharin Cocrystal

Oxcarbazepine (OXCBZ) is an antiepileptic drug with low aqueous solubility, and its dissolution is the rate limiting step for absorption. The present work investigates three muticomponent solid forms of OXCBZ with water-soluble coformers with an aim to enhance its solubility and in vivo performance. The experiments based on the solution method yielded two cocrystals, with succinic acid (<b>1</b>) and saccharin (<b>2</b>) and a solvate with acetic acid (<b>3</b>). Compound <b>1</b> was identified by single crystal X-ray diffraction (XRD) as a solvated cocrystal involving eight molecules of OXCBZ, four molecules of succinic acid, and four molecules of chloroform in the unit cell. The structural changes upon desolvation of cocrystal <b>1</b> have also been examined. Single crystals of compounds <b>2</b> and <b>3</b> could not be obtained in a size suitable for single crystal X-ray analysis and thus was studied by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, powder XRD, Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. Furthermore, the powder dissolution of compounds <b>1</b> (desolvated form), <b>2</b>, <b>3</b>, and OXCBZ was performed in an acidic aqueous medium and analyzed by high performance liquid chromatography. Their physical stability was also assessed. The cocrystal with saccharin showed a significant improvement in the solubility of OXCBZ in aqueous conditions and exhibited a lower ED₅₀ value as compared to pure OXCBZ

Crystal Structures and Physicochemical Properties of Four New Lamotrigine Multicomponent Forms

In the present study, four new multicomponent forms of lamotrigine (LTG) with selected carboxylic acids, viz. acetic acid, propionic acid, sorbic acid, and glutaric acid, have been identified. Preliminary solid-state characterization was done by differential scanning calorimetry/thermogravimetric, infrared, and powder X-ray diffraction techniques. X-ray single-crystal structure analysis confirmed the proton transfer, stoichiometry, and the molecular composition, revealing all of these to be a new salt/salt-cocrystal/salt monosolvate monohydrate of LTG. All four compounds exhibited both the aminopyridine dimer of LTG (motif 4) and cation–anion dimers between protonated LTG and the carboxylate anion in their crystal structures. Further, these new crystal forms were subjected to solubility studies in water, powder dissolution studies in 0.1 N HCl, and stability studies under humid conditions in comparison with pure LTG base. The solubility of these compounds in water is significantly enhanced compared with that of pure base, which is attributed to the type of packing motifs present in their crystal structures as well as to the lowering of the pH by the acidic coformers. Solid residues of all forms remaining after solubility and dissolution experiments were also assessed for any transformation in water and acidic medium

Crystal Structures and Physicochemical Properties of Four New Lamotrigine Multicomponent Forms

In the present study, four new multicomponent forms of lamotrigine (LTG) with selected carboxylic acids, viz. acetic acid, propionic acid, sorbic acid, and glutaric acid, have been identified. Preliminary solid-state characterization was done by differential scanning calorimetry/thermogravimetric, infrared, and powder X-ray diffraction techniques. X-ray single-crystal structure analysis confirmed the proton transfer, stoichiometry, and the molecular composition, revealing all of these to be a new salt/salt-cocrystal/salt monosolvate monohydrate of LTG. All four compounds exhibited both the aminopyridine dimer of LTG (motif 4) and cation–anion dimers between protonated LTG and the carboxylate anion in their crystal structures. Further, these new crystal forms were subjected to solubility studies in water, powder dissolution studies in 0.1 N HCl, and stability studies under humid conditions in comparison with pure LTG base. The solubility of these compounds in water is significantly enhanced compared with that of pure base, which is attributed to the type of packing motifs present in their crystal structures as well as to the lowering of the pH by the acidic coformers. Solid residues of all forms remaining after solubility and dissolution experiments were also assessed for any transformation in water and acidic medium