Solvates and polymorphs of rebamipide: preparation, characterization, and physicochemical analysis

Xiong, Xiaopeng; Du, Qiaohong; Zeng, Xia; He, Jiawei; Yang, Hongqin; Li, Hui

doi:10.1039/c7ra02895d

Cited by 23 publications

(13 citation statements)

References 33 publications

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“…All of the stored RB samples were powdery and fluid. It was reported that there are several RB pseudo-polymorphisms (i.e., monohydrate) and RB form II [ 42 , 43 ]. In the case of bulk RB storage at low ( Figure 2 B) and high humidity ( Figure 2 C), there was no pseudo-polymorphic or polymorphic transformation in the stored bulk RB sample, indicated by no change in the diffractogram pattern at RH 30% and RH 75% for four weeks.…”

Section: Resultsmentioning

confidence: 99%

Effect of Polymers and Storage Relative Humidity on Amorphous Rebamipide and Its Solid Dispersion Transformation: Multiple Spectra Chemometrics of Powder X-Ray Diffraction and Near-Infrared Spectroscopy

et al. 2020

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This study aimed to investigate the effect of polymers and storage relative humidity on amorphous rebamipide (RB) and its solid dispersion phase transformation using chemometrics based on multiple datasets. The amorphous RB was prepared using particle mixture and grinding methods with hydroxypropyl cellulose, polyvinylpyrrolidone, and sodium dodecyl sulfate. Prepared amorphous RB and solid dispersion samples were stored under a relative humidity of 30% and 75% for four weeks. Infrared spectra of the dispersion samples suggested that the hydrogen bond network was constructed among quinolinone, carbonyl acid, and amide of RB and other polymers. The dataset combining near-infrared (NIR) spectra and powder X-ray diffractograms were applied to principal component analysis (PCA). The relationship between diffractograms and NIR spectra was evaluated using loadings and the PCA score. The multiple spectra analysis is useful for evaluating model amorphous active pharmaceutical ingredients without a standard sample.

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Section: Resultsmentioning

confidence: 99%

Effect of Polymers and Storage Relative Humidity on Amorphous Rebamipide and Its Solid Dispersion Transformation: Multiple Spectra Chemometrics of Powder X-Ray Diffraction and Near-Infrared Spectroscopy

et al. 2020

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“… 14 − 16 Solvate formation is achieved when drug substances are exposed to different solvents during the crystallization process. 17 , 18 The crystallization process includes fast solvent evaporation, slow solvent evaporation, recrystallization from the required solvent, vapor diffusion, solvent/antisolvent precipitation, cooling crystallization, and slurry-mediated solvate formation. 19 However, in most cases, solvated forms have challenges toward physical and chemical stability, or in some cases, they may improve chemical stability.…”

Section: Introductionmentioning

confidence: 99%

Stable Fatty Acid Solvates of Dasatinib, a Tyrosine Kinase Inhibitor: Prediction, Process, and Physicochemical Properties

et al. 2022

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Exploration of alternate solid forms for dasatinib, a potent oncogene tyrosine kinase inhibitor classified under Biopharmaceutics Classification System (BCS) class II drugs with low water solubility and high permeability, has been performed using COSMO-RS excess enthalpy (Hex) to increase dissolution. The theoretical prediction resulted in the potential for the formation of C 6 –C 8 fatty acid solvates with dasatinib. A crystallization process has been identified for the preparation of the predicted solvates and successfully scaled up till the 100 g level. The fatty acid solvates are completely characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. Unique powder X-ray diffraction patterns and powder indexing of C 6 –C 8 fatty acid solvates indicate the purity of the solid phase. The red shift in the acid carbonyl stretching frequency of C 6 –C 8 fatty acids in FT-IR spectra and the intactness of the fatty acid proton in 1 H-NMR spectra provide evidence for solvate formation. The stoichiometry of active pharmaceutical ingredients (APIs) with solvent in solvates is measured using TGA and 1 H-NMR spectroscopy. Dasatinib C 6 –C 8 fatty acid solvates were found to retain their solid form under various stress and pharmaceutical processing conditions. In addition, they exhibited improved powder dissolution over dasatinib Form H1-7 by 2.2-fold. They also showed stability at 40 °C and 75% RH for 3 months. C 8 fatty acid is a USFDA GRAS listed solvent, and hence may be a viable option for drug product development.

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“…Solvate is very often used in the pharmaceutical industry, although it has uncontrolled physicochemical properties. However, a solvent with the right solvent can improve physicochemical stability 11 .…”

Section: Introductionmentioning

confidence: 99%

A Review on Solids State of Characterization Method in Pharmaceuticals

Sopyan¹,

N²,

Hs³

et al. 2019

Int. Res. J. Pharm.

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The solid form in pharmacy is generally classified into two types, i.e. stable and unstable amorphous solids. In addition, there are also several types of solids, such as disperse solids, solvates, hydrates, and nanoparticles. Comparing is done by several methods that have been used in general for solid characterization. Methods like X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR), Raman Spectroscopy (RS), Nuclear Magnetic Resonance (NMR), Density Measurement (DM), Thermal Analysis (TA), Supercritical Solvent (CSS), Supercritical Anti-Solvent (SAS) and Atomization Anti-Solvent (AAS) were used in general in solid-state characterization. The choice of method to be used depends on the desired information requirement of the solid. In general, the method used is more than one characterization technique for reached comprehensive analysis.

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Solvates and polymorphs of rebamipide: preparation, characterization, and physicochemical analysis

Abstract: Preparation and characterization of four solvates and three novel polymorphs of rebamipide, and investigations on the stability, solubility, and dissolution rate of the stable solid forms.

Cited by 23 publications

References 33 publications

Effect of Polymers and Storage Relative Humidity on Amorphous Rebamipide and Its Solid Dispersion Transformation: Multiple Spectra Chemometrics of Powder X-Ray Diffraction and Near-Infrared Spectroscopy

Effect of Polymers and Storage Relative Humidity on Amorphous Rebamipide and Its Solid Dispersion Transformation: Multiple Spectra Chemometrics of Powder X-Ray Diffraction and Near-Infrared Spectroscopy

Stable Fatty Acid Solvates of Dasatinib, a Tyrosine Kinase Inhibitor: Prediction, Process, and Physicochemical Properties

A Review on Solids State of Characterization Method in Pharmaceuticals

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