Polymorphism and Phase Transitions

Nie, Haichen; Byrn, Stephen R.

doi:10.1002/9781119046233.ch5

Cited by 4 publications

(2 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from nonambient conditions, phase transitions at ambient conditions are also commonly observed in molecular crystals, − particularly, in pharmaceutics. Because α- and β-forms are found to undergo a phase transition at high temperatures, the stability of the samples for extended duration at ambient conditions has been investigated by PXRD patterns to monitor the process.…”

Section: Results and Discussionmentioning

confidence: 99%

Unusual In Situ Transformation of Metastable Co-Crystal Forms into a Stable Form, in Solution and Solid State, and the [2 + 2] Photochemical Reactivity in the Crystalline Forms

Easmin

Pedireddi

2023

Crystal Growth & Design

View full text Add to dashboard Cite

Isolation of multiple composition co-crystals from a one-pot crystallization flask and in situ transformations of the crystals are not common phenomena. We describe, herein, thoroughly characterized three unusual co-crystals of citric acid (CA) and 1,2-bis(4-pyridyl)ethene (bpyee) with different molecular compositions (1:1, α; 2:2, β; and 2:3, γ) that were obtained from a one-pot crystallization flask of a CH3OH solution with equimolar co-formers. The three co-crystals can be distinguished by their morphology and appearance at various stages of the crystallization process. In the first instance, needle-shaped (β) crystals are formed on the edge of the flask, followed by plates (γ) in the bulk of the solution, and finally, the entire flask with only rod-shaped crystals (α), indicating the in situ conversion of β- and γ-forms into α-form. Interestingly, in the solid state, isolated crystals are observed to undergo conversion, but in a different way than solution growth, as characterized by in situ variable-temperature powder X-ray diffraction, with β- and α-forms converting into γ-form. Furthermore, all of the forms undergo [2 + 2] photochemical reactivity upon UV irradiation due to the favorable Schmidt’s photoreactive distance between the adjacent bpyee molecules in α- and γ-forms, with the former following a single-crystal-to-single-crystal transformation process also, while β-form, despite having bpyee molecules separated by 7.68 Å, through conversion into γ-form.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Unusual In Situ Transformation of Metastable Co-Crystal Forms into a Stable Form, in Solution and Solid State, and the [2 + 2] Photochemical Reactivity in the Crystalline Forms

Easmin

Pedireddi

2023

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…Raman spectroscopy, which provides molecular insight of the drug substance in the solid state, has been extensively used for qualitative and quantitative characterization of phase transitions and polymorphic interconversions between different solid-state forms of APIs in drug products. − For example, Raman spectroscopy combined with chemometric models can be applied to quantitatively monitor pharmaceutical salt-to-free base conversions in tablet matrices . Moreover, it has been reported that Raman spectroscopy is capable of detecting minute level polymorphic conversions as well as amorphization induced by shear stress during compaction. − However, the majority of the previous studies measured the polymorphic transformation of APIs after the powder compacts were ejected from the die. , …”

Section: Introductionmentioning

confidence: 99%

Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy

et al. 2020

Self Cite

View full text Add to dashboard Cite

The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mechanical Raman spectroscopy. The fit-for-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact’s relative density and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy approach enables the simultaneous detection of mechanical and chemical information of the powder compact throughout the tableting process.

show abstract

A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

Nie

Klinzing

2022

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Polymorphism and Phase Transitions

Cited by 4 publications

References 151 publications

Unusual In Situ Transformation of Metastable Co-Crystal Forms into a Stable Form, in Solution and Solid State, and the [2 + 2] Photochemical Reactivity in the Crystalline Forms

Unusual In Situ Transformation of Metastable Co-Crystal Forms into a Stable Form, in Solution and Solid State, and the [2 + 2] Photochemical Reactivity in the Crystalline Forms

Understanding Dynamics of Polymorphic Conversion during the Tableting Process Using In Situ Mechanical Raman Spectroscopy

A comparative study of applying backscattering and transmission Raman spectroscopy to quantify solid-state form conversion in pharmaceutical tablets

Contact Info

Product

Resources

About