Solid–Liquid Phase Equilibrium and Ternary Phase Diagrams of Telmisartan-Saccharin Cocrystal in Methanol, Ethanol, and Methanol/Chloroform Mixtures at 298.15 and 313.15 K

Abstract

In this work, ternary phase diagrams of telmisartan-saccharin (TEL-SAC) cocrystal in methanol, ethanol, and quasi-ternary sections of the quaternary system TEL-SAC–chloroform–methanol were determined at 298.15 and 308.15 K. The results show that the stable region of cocrystal is greatly biased towards SAC in methanol and ethanol; this is due to the large solubility difference between TEL and SAC. In the mixed solvent of chloroform and methanol, the cocrystal stable region appears at the center of the whole phase diagram when the mass fraction of chloroform is 80%, which indicated that the solubility difference between TEL and SAC in the mixed solvent was relatively small. Moreover, the solubility behavior of TEL-SAC cocrystal was studied and the results showed that the solution complexation model in methanol and ethanol was 1:1 + 1:2, and the complexation model in chloroform and binary mixtures of chloroform/methanol was 1:1.

Effect of Additives on Preferential Crystallization for the Chiral Resolution of Citrulline: Experimental, Statistical, and Molecular Dynamics Simulation Studies

“…The 5 mg sample was poured into a pinhole aluminum crucible and heated from room temperature to 550 K under a nitrogen atmosphere at 10 K•min −1 . 38 3.3. Solubility Measurement.…”

“…The thermal analyses of l - and dl -citrulline were carried out, respectively, with a Q2500 differential scanning calorimeter and a Q500 thermogravimetric analyzer (TA, Wilmington, DE). The 5 mg sample was poured into a pinhole aluminum crucible and heated from room temperature to 550 K under a nitrogen atmosphere at 10 K·min –1 …”

Solubility correlation by model with partial molar volume

“…[ 1 ] Most of the crystallization processes employ the addition of an anti‐solvent and involve simultaneous alterations in the temperature of the solution. [ 2 ] Experimental measurement of solubility is the most reliable method and provides the most accurate solubility data [ 3,4 ] ; however, it has limitations, including long time and money consumption. To overcome these limitations, mathematical models could be used for prediction purposes or detecting possible outliers for re‐determination.…”

Shortcut Method for the Prediction of the Cocrystal Solubility Line

“…From a biological standpoint, solubility determines the concentration of the API in systemic circulation so it must be fine-tuned for achieving the required pharmacological response . From an engineering perspective, solubility curves are necessary for any crystallization process design and development. , Thus, several studies have been devoted to improving API solubility via cocrystallization with a coformer (CF) as well as finding the region in the phase diagram that favors cocrystal formation. − For instance, Darwish et al have successfully prepared a new 1:1 theophylline–aspirin cocrystal and then constructed the ternary phase diagram (TPD) to identify stable regions for cocrystal formation …”

“…Furthermore, recent reports propose mathematical models to describe the solubility of cocrystal species using chemical equilibrium models. , Nehm et al used a chemical equilibrium approach to develop a model to describe the isothermal solubility behavior of carbamazepine (CBZ)–nicotinamide (NIC) cocrystals in terms of a chemical reaction ( K s ) and complexation constants ( K API:coformer ) under the assumption that activity coefficients are unity. The molecular complexation in the solution could involve several stoichiometric ratios of API/CF such as K 11 for 1:1 and K 12 for the 1:2 API/CF ratio, depending on the favorable binding of functional groups in the two molecules.…”