Binary to ternary drug–drug molecular adducts of the antihypertensive drug ketanserin (KTS) with advanced physicochemical properties

Rout, Smruti Rekha; Kenguva, Gowtham; Giri, Lopamudra; Kar, Ananya; Dandela, Rambabu

doi:10.1039/d2cc06666a

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…One of the main reasons for the limited number of ternary and higher-order cocrystals is the challenge associated with screening and synthesis of the desired solids . An increase in the number of reactants may result in increased competition between different crystalline phases, including initial compounds and/or lower-order cocrystals and their hydrates/solvates/polymorphs …”

Section: Introductionmentioning

confidence: 99%

Rational Design of the Carbamazepine Ternary Cocrystals

Boycov,

Drozd,

Manin

et al. 2024

Crystal Growth & Design

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The first ternary cocrystals of carbamazepine (CBZ) were successfully identified through a large-scale screening. A design strategy involved the use of an aliphatic dicarboxylic acid to link CBZ and a third component into a hydrogen-bonded trimeric unit. Out of the 10 dicarboxylic acids tested, only malonic acid produced a positive response in the attempt to obtain the CBZ ternary cocrystals with benzamide and picolinamide. The crystal structures of the novel ternary cocrystals obtained by vapor diffusion crystallization were determined by single-crystal X-ray diffraction. Structural analysis revealed that the ternary cocrystals are isostructural and exhibit the packing of trimers into ladder-like chains. The relationship between the CBZ binary and ternary cocrystals was confirmed by comparing the crystal structures. The cocrystal solubility method was applied to estimate the thermodynamic parameters of the ternary cocrystal formation. The negative values of the Gibbs free energy, enthalpy, and entropy indicate that the reaction of ternary cocrystal formation is a thermodynamically favored process and driven by enthalpy. Despite the isostructural nature, the physicochemical properties of the ternary cocrystals, including melting point and thermodynamic solubility, are strongly influenced by the variable coformer.

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Section: Introductionmentioning

confidence: 99%

Rational Design of the Carbamazepine Ternary Cocrystals

Boycov,

Drozd,

Manin

et al. 2024

Crystal Growth & Design

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show abstract

“…The analysis method employs the heating of the sample in isothermal or non-isothermal conditions and evaluating the mass loss, phase transitions, and polymorphic transformations [11]. Furthermore, thermal analysis offers valuable information about the thermal stability of the inclusion complexes of the APIs with cyclodextrins [12][13][14], binary or ternary adducts [15], and cocrystals [16,17].…”

Section: Introductionmentioning

confidence: 99%

Kinetic Investigation of the Oxidative Thermal Decomposition of Levonorgestrel

Ridichie,

Ledeţi,

Peter

et al. 2023

Processes

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In this study, we have focused on studying the heterogenous degradation kinetics regarding the decomposition of the emergency contraceptive agent levonorgestrel (LNG), which is a second-generation synthetic progestogen that is the active component of the racemic mixture of norgestrel. The degradation processes of the active pharmaceutical ingredient (API) were compared with the ones obtained from a model system containing the API along with the excipients that are found in a commercialized pharmaceutical formulation in a mass ratio of 1:1 (LNGMIX), in order to observe if the excipients have a stabilizing or destabilizing effect on the degradation of this progestogen. To achieve this, the following investigational methods were used: FTIR (Fourier transform infrared) spectroscopy and thermal analysis (TG/DTG/DSC analysis). For the kinetic analysis, the data obtained from two main decomposition processes observed on the DTG curves were used and processed with a preliminary method, namely ASTM E698, and two isoconversional methods: Friedman and Flynn–Wall–Ozawa. The isoconversional study revealed that the decomposition mechanisms of both LNG and LNGMIX are complex, and the excipients have a stabilizing effect on the decomposition of the API in tablet.

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“…The analysis method implies the heating of the sample in isothermal or nonisothermal conditions and evaluating the mass loss, phase transitions and polymorphic transformations [11]. Even more, thermal analysis offers valuable information about the thermal stability of inclusion complexes of the APIs with cyclodextrins [12][13][14], binary or ternary adducts [15] and cocrystals [16,17].…”

Section: Introductionmentioning

confidence: 99%

Kinetic Investigation of Oxidative Thermal Decomposition of Levonorgestrel

Ridichie,

Ledeţi,

Peter

et al. 2023

Preprint

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In this study, we have focused on studying the heterogenous degradation kinetics of regarding the decomposition of emergency contraceptive agent levonorgestrel (LNG), which is a second-generation synthetic progestogen that is the active component of the racemic mixture of norgestrel. The degradation processes of the active pharmaceutical ingredient (API) were compared with the ones obtained from model system containing the API along with the excipients that are found in a commercialized pharmaceutical formulation in a mass ratio of 1:1 (LNGMIX), in order to observe if the excipients have a stabilizing or destabilizing effect for the degradation of this progestogen. To achieve this, the following investigational methods were used: FTIR (Fourier transform infrared) spectroscopy and thermal analysis (TG/DTG/DSC analysis). For the kinetic analysis the data obtained from two main decomposition processes observed on the DTG curves were used and processed with a preliminary method, namely ASTM E698 and two isoconversional methods: Friedman and Flynn-Wall-Ozawa. The isoconversional study revealed that the decomposition mechanism of both LNG and LNGMIX are complex, and the excipients have a stabilizing effect over decomposition of API in tablet.

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Binary to ternary drug–drug molecular adducts of the antihypertensive drug ketanserin (KTS) with advanced physicochemical properties

Abstract: Focusing on reliable supramolecular synthons approach, novel molecular salts of the antihypertensive medication ketanserin (KTS) with benzoic acid derivatives (benzoic acid (BA), 2-hydoxybenzoic acid (2-HBA), 2,5-dihydroxybenzoic acid (2,5-DHBA)) are reported....

Cited by 6 publications

References 37 publications

Rational Design of the Carbamazepine Ternary Cocrystals

Rational Design of the Carbamazepine Ternary Cocrystals

Kinetic Investigation of the Oxidative Thermal Decomposition of Levonorgestrel

Kinetic Investigation of Oxidative Thermal Decomposition of Levonorgestrel

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