Quantification and modeling of nanomechanical properties of chlorpropamide α, β, and γ conformational polymorphs

Janković, Biljana; Joksimović, Tatjana; Stare, Jernej; Losev, Evgeniy A.; Zemtsova, Viktoriya; Srčič, Stanko; Болдырева, Е. В.

doi:10.1016/j.ejps.2017.06.013

Cited by 12 publications

(6 citation statements)

References 40 publications

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“…Progress has been made in in silico prediction. For example, various studies have found a strong correlation between experimentally determined mechanical data and predicted data. − …”

Section: Introductionmentioning

confidence: 98%

Utilizing Crystal Structures for Predicting Impact of Mechanical and Surface Properties on Particle Fracture

Halme

Quayle

Lill

et al. 2019

Crystal Growth & Design

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The micronization process of new compounds is usually performed based on an empirical basis with a limited understanding of input material properties and potential challenges. This study focuses on the understanding of the fracture behavior of small organic molecular crystals, by using particle shape and surface energy analysis techniques as well as molecular modeling tools. These methodologies enable us to generate new data and new ways of working that can provide crucial information for future pharmaceutical development. The shape, surface energy, and mechanical properties for four different drug substances were studied. This study showed that the crystal shape and the intermolecular interactions influence the dominant fracture mechanism. An in-depth knowledge of these together with the mechanical properties gives an insight of the fracture mechanism of small organic molecular crystals. In a second part, Partial Least Squares regression was applied to the data sets to model the size reduction ratio and d 90 of the micronized materials. Models were derived using multiple parameters.

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“…Progress has been made in in silico prediction. For example, various studies have found a strong correlation between experimentally determined mechanical data and predicted data. − …”

Section: Introductionmentioning

confidence: 98%

Utilizing Crystal Structures for Predicting Impact of Mechanical and Surface Properties on Particle Fracture

Halme

Quayle

Lill

et al. 2019

Crystal Growth & Design

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“…In addition, there is still minor elasticity and plastic deformation of particles in region I. 51 It is worth noting that a portion of the fresh-formed CPA-C was reverted back to CPA-A after dwelling and unloading/decompression. For example, it has been quantified that 30% CPA-A was converted to CPA-C under 60 MPa.…”

Section: Resultsmentioning

confidence: 97%

“…Less than 30% CPA-A to CPA-C conversion was observed in region I (Figure A), indicating that the CPA-A to CPA-C conversion is very sensitive and can be triggered by even slight mechanical forces in the low-pressure region. In addition, there is still minor elasticity and plastic deformation of particles in region I . It is worth noting that a portion of the fresh-formed CPA-C was reverted back to CPA-A after dwelling and unloading/decompression.…”

Section: Results and Discussionmentioning

confidence: 99%

“…It has been reported that the CPA-A crystalline solids have elasticity. 30,33,51 The CPA powder compact is elastically deformed and can be recovered during the decompression/unloading in region III where a clear discrepancy between the compression and the decompression curve in the Heckel plot was demonstrated (Figure 4B). 37 In Figure 6B, drastic changes in the relative density (Δ ln[1/(1 − D)]) of the CPA compact are demonstrated as additional evidence to support the elastic recovery of CPA.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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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.

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“…94-20-2) (CPA, see Figure ) is one of the sulfonylurea drugs that are often used for the treatment of type II diabetes. It has a molecular weight of 276.74 and a melting temperature of 398–401 K. As a first generation oral sulfonylurea drug, CPA has been used as a model compound to study pharmacological action, conformational polymorphs, crystal structure, and mechanical properties. − Crystallization is an important way for separation and purification of solid products, especially in the pharmaceutical industry. The crystallization process and conditions have a great influence on the crystal structure, particle size distribution, and fluidity of the product .…”

Section: Introductionmentioning

confidence: 99%

Solid–Liquid Equilibrium of Chlorpropamide in 14 Pure Solvents at Temperature of 283.15 to 323.15 K

Liu

Wang

Qu³

et al. 2020

J. Chem. Eng. Data

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In this paper, the solubility of chlorpropamide (CPA) in 14 solvents including 8 alcohols (ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, iso-butanol, n-pentanol, and isopentanol) and 6 acetate esters (ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, amyl acetate, and methyl propionate) at temperatures of 283.15 to 323.15 K and atmospheric pressure was determined using a laser method. The solubility as a function of temperature was regressed using modified Apelblat, Van’t Hoff, λh, Wilson, and nonrandom two-liquid (NRTL) models. On the basis of the experimental and the simulation results, the mixing properties of the solutions, that is, mixing Gibbs energy, enthalpy, and entropy, were estimated.

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Quantification and modeling of nanomechanical properties of chlorpropamide α, β, and γ conformational polymorphs

Cited by 12 publications

References 40 publications

Utilizing Crystal Structures for Predicting Impact of Mechanical and Surface Properties on Particle Fracture

Utilizing Crystal Structures for Predicting Impact of Mechanical and Surface Properties on Particle Fracture

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

Solid–Liquid Equilibrium of Chlorpropamide in 14 Pure Solvents at Temperature of 283.15 to 323.15 K

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