Low pressure phases

Légendre, B.; Bac, Pierre; German, Michael; Feutelais, Y.

doi:10.1007/s10973-009-0401-0

Cited by 10 publications

(11 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[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.

View full text Add to dashboard Cite

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.

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…The results of a separate thermogravimetric analysis of the α -IMC, also shown in Figure S-3 of the Supporting Information shows that ~0.5% of residual volatiles were occluded within the crystal after recrystallization. 48 On the basis of our analysis, compounds prior to tabulation were pure within the detection limits of the Raman and BCARS instruments used.…”

Section: Resultsmentioning

confidence: 99%

Multicomponent Chemical Imaging of Pharmaceutical Solid Dosage Forms with Broadband CARS Microscopy

et al. 2013

View full text Add to dashboard Cite

We compare a coherent Raman imaging modality, broadband coherent anti-Stokes Raman scattering (BCARS) microscopy, with spontaneous Raman microscopy for quantitative and qualitative assessment of multicomponent pharmaceuticals. Indomethacin was used as a model active pharmaceutical ingredient (API) and was analyzed in a tabulated solid dosage form, embedded within commonly used excipients. In comparison with wide-field spontaneous Raman chemical imaging, BCARS acquired images 10× faster, at higher spatiochemical resolution and with spectra of much higher SNR, eliminating the need for multivariate methods to identify chemical components. The significant increase in spatiochemical resolution allowed identification of an unanticipated API phase that was missed by the spontaneous wide-field method and bulk Raman spectroscopy. We confirmed the presence of the unanticipated API phase using confocal spontaneous Raman, which provided spatiochemical resolution similar to BCARS but at 100× slower acquisition times.

show abstract

“…Although the use of a mixture of DCM and MeOH as a solvent for dissolving IMC has been described [21], solubility data of IMC in these solvent mixtures have not been reported before. IMC has at least three polymorphs [22,23] and a strong tendency toward solvate formation in many solvents [24], which should be taken into account in the solubility measurements. For this reason, the formation of IMC solvates in solvent mixtures is also a subject of investigation.…”

Section: Introductionmentioning

confidence: 99%

Screening of Binary Solvent Mixtures and Solvate Formation of Indomethacin

Hellstén

Louhi-Kultanen

2011

Chem Eng & Technol

View full text Add to dashboard Cite

The applicability of solubility parameters and solvent activity in the screening of binary solvent mixtures was studied. The solubility of indomethacin was measured in binary mixtures of dichloromethane, acetone, and ethyl acetate with methanol and ethanol. Solubility extremes in the mixed solvents were observed. The solubility maxima were related to the excess Gibbs free energy of the solvents and the hydrogen bonding term of the Hansen solubility parameter. The solvates of indomethacin were characterized with a confocal Raman spectrometer, and the desolvation of the solvates was investigated with thermogravimetry.

show abstract

Low pressure phases

Cited by 10 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

Multicomponent Chemical Imaging of Pharmaceutical Solid Dosage Forms with Broadband CARS Microscopy

Screening of Binary Solvent Mixtures and Solvate Formation of Indomethacin

Contact Info

Product

Resources

About