Solvates of Indomethacin

Hamdi, Naceur; Feutelais, Y.; Yagoubi, Najet; Girolamo, D. de; Légendre, B.

doi:10.1023/b:jtan.0000032284.89029.06

Cited by 26 publications

(31 citation statements)

References 6 publications

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“…[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Recent studies by Surwase et al reported new crystalline forms of IMC and water driven phase transitions from an amorphous phase, in spite of years of studies. 23 The thermodynamically most stable form of indomethacin (g-IMC) has the space group symmetry P% 1 with Z 0 = 1.…”

Section: Resultsmentioning

confidence: 99%

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

Nartowski

Tedder

Braun

et al. 2015

Phys. Chem. Chem. Phys.

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The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate - ROY (259.3 g mol(-1)). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical - indomethacin (IMC, 357.8 g mol(-1)), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano-crystalline encapsulated organic solids.

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Section: Resultsmentioning

confidence: 99%

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

Nartowski

Tedder

Braun

et al. 2015

Phys. Chem. Chem. Phys.

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“…1) is known to form polymorphs (1); two of them, the a-and g-forms, have been structurally solved (2)(3)(4)(5). It can also form solvates (6), and its amorphous properties have been extensively studied (7). Formation of different polymorphs and solvates is well known to be caused by varying experimental conditions including growth media, solute concentrations and environmental temperature.…”

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confidence: 99%

The Polymorphism of Indomethacin: An Analysis by Density Functional Theory Calculations

Aubrey‐Medendorp

Swadley

2007

Pharm Res

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“…It has been reported earlier that the IMC form solvates when in contact with pure acetone or methanol, which was also confirmed in the present investigation. 30 However, analysis of the solid recovered from the equilibrated suspension at the end of the solubility measurement by XRPD (Supporting Information, Figure S2) indicated no solid phase transformation of γ-IMC to any of the solvates during the measurements. This observation suggested that the solid phase transformation from the γ-IMC to the acetone or methanol solvates can be retarded by the presence of water in the solvent, which could be attributed to the altered solute-solvent interactions.…”

Section: Solubility Of Indomethacin In Binary and Ternary Solvent MIXmentioning

confidence: 99%

Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control

Malwade

2019

Org. Process Res. Dev.

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Antisolvent crystallization of Indomethacin (IMC), a nonsteroidal anti-inflammatory drug, from a ternary solvent system (acetone-methanol-water) has been investigated in this work. Acetonemethanol (66.5-33.5 wt%) binary mixture was selected as a solvent based on the solubility of IMC reported earlier. Water was selected as an antisolvent based on the solubility of IMC measured in acetone-methanol-water mixtures at 25 °C. Unseeded and seeded antisolvent crystallization was carried out for two initial concentrations of IMC (and) with stepwise addition of 0, 1 0, 2 antisolvent. The acetone solvate of IMC was crystallized during the unseeded experiments, while the desired γ-IMC was obtained with a bimodal particle size distribution (PSD) during the experiments seeded with γ-IMC. A significant increase in the productivity was observed because of increased crystal yield and faster crystallization kinetics as compared to the crystallization processes reported earlier for the production of γ-IMC. Finally, the feasibility of IMC particle size tuning through the solvent-antisolvent (dissolution-growth) addition cycles was demonstrated successfully.

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Solvates of Indomethacin

Cited by 26 publications

References 6 publications

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

The Polymorphism of Indomethacin: An Analysis by Density Functional Theory Calculations

Antisolvent Crystallization of Indomethacin from a Ternary Solvent System with High Productivity, Better Polymorphism, and Particle Size Control

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