Thermodynamic stability and transformation of pharmaceutical polymorphs

Kitamura, Mitsutaka

doi:10.1351/pac200577030581

Cited by 7 publications

(4 citation statements)

References 13 publications

(20 reference statements)

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“…It is known that any crystallization process is composed of elementary dynamic acts of competitive nucleation and growth of mostly metastable forms and of their transformation to a stable form . The transformation from a metastable form to a stable crystalline form can also happen only after the completion of crystallization.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no basic reasons why such phenomena could not happen in pure organic crystalline substances. Discovery of such phenomena and their detailed investigation could significantly help in understanding formation of multiple metastable phases during crystallization of organic substances, the phenomenon known as monotropic polymorphism, extremely important in pharmaceutical practice . Here, we present a detailed description of such thermodynamically paradoxical transitions from a crystalline to a dense glassy state observed under atmospheric pressure in two polymorphic forms of rosiglitazone maleate (RM), an important pharmaceutical substance used as an insulin enhancer.…”

Section: Introductionmentioning

confidence: 99%

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Metastability and Instability of Organic Crystalline Substances

Randzio

Kutner

2008

J. Phys. Chem. B

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Discovery of an unexpected and thermodynamically paradoxical transition from a crystalline state to an amorphous dense glassy state induced in pure organic substances by a direct absorption of a quantity of heat under atmospheric pressure and its detailed analysis performed with the use of a sensitive scanning transitiometer are described. The obtained results present first experimental precise evidence for understanding the mechanism of such a structural instability of crystalline substances in the form of c-a transition. The observed c-a transition is a purely physical phenomenon, occurring between two nonequilibrium states, a metastable crystalline phase and a dense glass, occurring through a local transient phenomenon of virtual melting. The metastable state of a crystalline substance can be caused by existence of a number of crystalline imperfections created either during crystallization or by external actions. By measuring extremely sensitive energetic effects, we found the present method to be helpful for quantitative determination of the critical number of imperfections in a crystalline solid, which make it metastable and for an indication under which conditions such a metastable crystalline form becomes unstable. By performing the transitiometric analysis of c-a transitions with two polymorphs of rosiglitazone maleate, we demonstrated to what extent this analysis is important in investigation of stability of crystalline components of drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metastability and Instability of Organic Crystalline Substances

Randzio

Kutner

2008

J. Phys. Chem. B

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“…The conformation of Phase 1 and Phase 2 is identical, 5 which corresponds to the small difference in the chemical potential between the polymorphs resulting in similar solubility profiles. 39 According to Fig. 14, the most favourable, seeded, cooling crystallisation is feasible as the slope of the solubility curve allows the application of this method.…”

Section: Crystallisationmentioning

confidence: 99%

Crystallisation of a salt hydrate with a complex solid form landscape

et al. 2017

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Different approaches were utilized to assess the thermodynamic stability relationship between four distinct hemihydrates of sitagliptin L-tartrate (SLT). These phases are true polymorphs, having the same chemical composition and molar ratio of water, but different arrangement in the crystal lattice. The general approaches (Burger and Ramberger rules) have only limited applicability, but indicated a monotropic relationship between Phase 1 and Phase 2. The crystallisation and transformation behaviour of the polymorphs was strongly influenced by the solvent composition. As the stability thereof was found to be solvent-dependent, the application of the van't Hoff plot or the solvent-mediated transformation did not unambiguously reveal the relative stability of the forms. Experiments were carried out in an endeavour to determine the most suitable concentration trajectory for cooling crystallisation of the selected candidate and prevent concomitant crystallisation. The application of in situ monitoring techniques, such as FTIR-ATR and FBRM, offered great potential for process optimization and control.

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“…Phase transitions including polymorph interconversion, hydrate formation, and solvate desolvation − may happen under different processes, such as crystallization, granulation, compaction, drying, storage, and transport. It will further affect the performance (stability, − particle size and shape, − flowability, hygroscopicity, − and solubility − ) of the active pharmaceutical ingredients . Consequently, a thorough characterization of all possible pharmaceutical polymorphs and investigation of the phase transformation process are crucial for selecting the optimal solid form for development. − Furthermore, mapping the solid form landscapes will increase the understanding of the physicochemical properties and crystallization behavior of crystal forms, which can contribute to product design and process development.…”

Section: Introductionmentioning

confidence: 99%

Exploring Solid Form Landscape of Anticancer Drug Dimethylaminomicheliolide Fumarate: Crystal Structures Analysis, Phase Transformation Behavior, and Physicochemical Properties Characterization

Wang

et al. 2021

Crystal Growth & Design

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Brain tumors are still the deadliest among all types of cancer even after decades of extensive research. Glioblastoma is the most common and aggressive form of primary malignant brain tumors. As an efficient NF-κB inhibitor, dimethylaminomicheliolide fumarate has shown excellent therapeutic effect for glioblastoma in clinical trials. To date, no reports about the solid forms of dimethylaminomicheliolide fumarate have been disclosed. Dimethylaminomicheliolide fumarate was thus an interesting subject for polymorphism exploration. In this work, four solid forms (Forms B, C, D, and E) were successfully obtained. The crystal structures exhibit similarity in molecular conformation and packing arrangements between Form C and Form E. The PXRD patterns and phase transition behavior suggest that Form B and Form D are likely to have similarities. Hirshfeld surfaces were generated for a better understanding of the relationships of different crystal forms. They were also characterized and evaluated by thermal analysis, polarizing microscope, and dynamic vapor sorption as well as powder properties tests. The comprehensive exploration of the solid form landscape provided essential knowledge for product development and quality control of this potential drug.

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Thermodynamic stability and transformation of pharmaceutical polymorphs

Cited by 7 publications

References 13 publications

Metastability and Instability of Organic Crystalline Substances

Metastability and Instability of Organic Crystalline Substances

Crystallisation of a salt hydrate with a complex solid form landscape

Exploring Solid Form Landscape of Anticancer Drug Dimethylaminomicheliolide Fumarate: Crystal Structures Analysis, Phase Transformation Behavior, and Physicochemical Properties Characterization

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