Polymorphism of gemfibrozil: Investigation by thermal and spectroscopic methods

Holanda, Bruno B.C.; Bannach, Gilbert; Silva, M. Ramos; Eusébio, M. Ermelinda S.; Castro, Ricardo A. E.

doi:10.1016/j.tca.2019.03.026

Cited by 6 publications

(6 citation statements)

References 22 publications

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“…Holanda studied the polymorphism of gemfibrozil, which has two forms. 47 In this work, no new diffraction peaks appear at 12.28°, suggesting no change in the crystal form of Gem. Meanwhile, the characteristic peaks of the surfactant are not observed in the PXRD results of the spherical products.…”

Section: ■ Results and Discussionmentioning

confidence: 51%

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Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil

Wang

Liu

Guo

et al. 2022

ACS Sustainable Chem. Eng.

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Granulation is an important method to increase the fluidity of compounds, especially drugs with needle-like shapes. Another function of granulation is to mix active pharmaceutical ingredients (APIs) and excipients. In this research, oiling-out spherical agglomeration technology was used to obtain single- and multicomponent drug spherical particles of gemfibrozil, which can be directly compressed. This technology is carried out by simply heating and quenching operations in nonorganic solvents. Compared with the current granulation technology, it is estimated that approximately 400 metric tons (MT) of organic solvents per year can be saved for every 100 MT of gemfibrozil production. Meanwhile, based on the binary oiling-out phase diagram, the spherical particles of gemfibrozil were prepared with high bulk density (0.71 g cm–3), good sphericity (>80%), high yield (>95%), and adjustable particle size distribution, and the flowability is improved by 47.37%. Furthermore, the multicomponent functional particles of gemfibrozil and nimodipine for drug combination with the good morphology and uniform distribution of components were obtained by establishing ternary oiling-out phase diagrams. The results of tablet compaction showed a 4 times increase in tabletability from single-component spherical particles and a 2.7 times increase from multicomponent spherical particles compared to commercial powders. On the other hand, the failing case of gemfibrozil and simvastatin indicated that the binding energy between molecules is the key point of this method, and this result revealed the limitation of the oiling-out spherical agglomeration method for the current selection strategy of drugs. This work provided an experimental and theoretical basis for the further application of this green technology.

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Section: ■ Results and Discussionmentioning

confidence: 51%

“…In accordance with PDF#42-1867, it can be seen that the characteristic peaks of particles are correspondingly consistent. Holanda studied the polymorphism of gemfibrozil, which has two forms . In this work, no new diffraction peaks appear at 12.28°, suggesting no change in the crystal form of Gem.…”

Section: Resultsmentioning

confidence: 80%

Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil

Wang

Liu

Guo

et al. 2022

ACS Sustainable Chem. Eng.

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“…This ability suggests that even after heating well above the melting point, temperature-induced nucleation into the initial crystal structure is observed upon cooling below the melting temperature . This intriguing phenomenon is frequently observed during the crystallization of slowly crystallizing materials like polymers and glasses. , In the case of polymer crystallization, a specific polymorph could appear at temperatures far above the melting point due to heterogeneous nucleation at impurities, by homogeneous nucleation from the internal structure in the melt (self-nucleation), or slightly above the melting temperature due to crystal fragments in the melt (self-seeding). − However, the melt memory effect is hardly known for molecular crystals, despite the fact that it can be of technological importance. ,− Here, the melt memory effect is evidenced for three different solvates of the molecule OEG-BTBT; recrystallization back to their initial structure is observed even after annealing far above their melting temperatures.…”

Section: Introductionmentioning

confidence: 99%

Memory Effect by Melt Crystallization Observed in Polymorphs of a Benzothieno-Benzothiophene Derivative

James,

Greco,

Devaux

et al. 2023

Crystal Growth & Design

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This work provides a comprehensive illustration of a crystalline melt memory effect recorded for three solvates of the 2,7-bis(2-(2-methoxyethoxy)ethoxy)benzo[b]benzo [4,5] thieno [2,3-d]thiophene (OEG-BTBT) molecule with dichloromethane (DCM) molecules. Combined optical microscopy and X-ray diffraction measurements at different temperatures are used to get an overview of the structural and morphological properties like melting points, isotropic transition temperatures, induction times, and crystallization kinetics of the three forms. An outstanding observation is made upon annealing the three polymorphs at temperatures well above their respective melting points as well as above the optical clearance temperature. After cooling back to room temperature, recrystallization results in the formation of the initial phase present before the annealing process. This melt memory effect is observed for all three solvates. These observations can be correlated to the strong interaction between the DCM molecules and the oligoethylene glycol side chains, even in the molten state. This conclusion rationalizes the experimental observation made upon solvent vapor annealing of the crystalline sample with DCM, which unambiguously transformed the system into a disordered state.

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“…Crystallization is commonly used as a purification technique for APIs in the pharmaceutical industry . Controlling the stable polymorph of API during the crystallization process is well investigated. − However, crystallization and isolation of metastable polymorphs with high purity are rarely reported since it is hard to stop/hinder the transformation process from a metastable form into a stable form using the conventional methods . Even if metastable forms of APIs can be produced by adding polymers or other techniques, the stability of products is poor (i.e., the metastable form readily transforms into other more stable forms).…”

Section: Introductionmentioning

confidence: 99%

Application of Phenyl-Functionalized Porous Silica for the Selective Crystallization of Carbamazepine Metastable Form II

Ouyang

Chen

et al. 2021

Ind. Eng. Chem. Res.

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Polymorphic nucleation of carbamazepine (CBZ) in several solvents (ethanol, 2-propanol, acetone, acetonitrile, toluene, and nitromethane) was investigated with different functionalized porous silica templates. It was found that the introduction of silica templates with different surface chemistries such as −OH, −NH2, and −phenyl affected the polymorphic outcomes. At a low supersaturation ratio, stable form III of CBZ was prone to nucleate as expected. However, the results in this work confirmed that a phenyl-functionalized porous silica template could crystallize and maintain metastable form II of CBZ at a low supersaturation ratio for a long time. In terms of the underlying mechanism, the aromatic–aromatic interaction between the surface of phenyl-functionalized silica and the CBZ molecule played an important role in stabilizing metastable form II. The influence of the amount of silica templates on the polymorph formation was also investigated. Our results will help to crystallize and maintain metastable materials, even at a low supersaturation ratio.

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Polymorphism of gemfibrozil: Investigation by thermal and spectroscopic methods

Cited by 6 publications

References 22 publications

Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil

Design of Single and Multicomponent Drug Spherical Particles with Improved Powder Properties in Water Instead of Organic Solvents: A Case Study of Gemfibrozil

Memory Effect by Melt Crystallization Observed in Polymorphs of a Benzothieno-Benzothiophene Derivative

Application of Phenyl-Functionalized Porous Silica for the Selective Crystallization of Carbamazepine Metastable Form II

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