Hot stage microscopy and its applications in pharmaceutical characterization

Kumar, Arun; Singh, Pritam; Nanda, Arun

doi:10.1186/s42649-020-00032-9

Cited by 37 publications

(25 citation statements)

References 50 publications

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“…SEM can detect the properties of a given sample such as surface topography, composition, and crystal orientation in the nanoscale range. It can also provide information about crystal defects (if any) by modifying different intensities of the incident beam of radiation (Naresh- Kumar et al, 2020).…”

Section: Characterization Methods Of Cocrystalmentioning

confidence: 99%

“…DSC and TGA are reliable techniques to determine thermal properties, but cocrystal screening to determine properties such as solid-state transition, miscibility, crystalline nature, and morphology can be better studied using hot stage microscopy (HSM) ( Malamatari et al, 2017 ). HSM is one of the widely used techniques for cocrystal, as it is relatively faster as it eliminates the need to prepare cocrystal from conventional methods ( Kumar et al, 2020 ). Besides FTIR, Raman spectroscopy is known to be one of the vibrational spectroscopic techniques as it can be used to predict various bands, whether there is the formation of a new crystal which can be observed by the change in the vibrational frequency of the obtained sample ( Elbagerma et al, 2010 ).…”

Section: Characterization Methods Of Cocrystalmentioning

confidence: 99%

See 1 more Smart Citation

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Bandaru¹,

Rout²,

Kenguva³

et al. 2021

Front. Pharmacol.

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The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.

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Section: Characterization Methods Of Cocrystalmentioning

confidence: 99%

Section: Characterization Methods Of Cocrystalmentioning

confidence: 99%

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Bandaru¹,

Rout²,

Kenguva³

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…HSM is a well-known thermal analytical technique coupled with polarized microscopy for solid-state characterization of pharmaceuticals as a function of time and temperature. , It supports real-time observation of samples undergoing thermal events and reveals the morphological changes, glass transitions, polymorphism, phase transitions, melting points, crystallization process, de-solvation, and so forth occurring in the samples during heating. − In the present study, this technique was employed to qualitatively observe the melting, physical changes, or solid-phase transformation taking place in RFX and its polymeric PPTS with increasing temperature. As depicted from Figure A, the RFX crystals started to shrink at 241.6 °C, followed by the approximate melting in the narrow range of 253.3–257.5 °C.…”

Section: Resultsmentioning

confidence: 92%

Elucidating the Molecular Mechanism of Drug–Polymer Interplay in a Polymeric Supersaturated System of Rifaximin

et al. 2021

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Supersaturated drug delivery system (SDDS) enables the solubility and sustained membrane transport of poorly water-soluble drugs. SDDS provides higher drug concentration in the dispersed phase and equilibrium in the continuous phase, which corresponds to amorphous solubility of the drug. Rifaximin (RFX) is a nonabsorbable BCS class IV drug approved for the treatment of irritable bowel syndrome and effective against Helicobacter pylori. RFX shows slow crystallization and precipitation in an acidic pH of 1.2−2, leading to obliteration of its activity in the gastrointestinal tract. The objective of the present study is to inhibit the precipitation of RFX, involving screening of polymers at different concentrations, using an in-house developed microarray plate method and solubility studies which set forth hydroxypropyl methylcellulose (HPMC) E15, Soluplus, and polyvinyl alcohol to be effective precipitation inhibitors (PIs). Drug− polymer precipitates (PPTS) are examined for surface morphology by scanning electron microscopy, solid-phase transformation by hot stage microscopy, the nature of PPTS by polarized light microscopy, and drug−polymer interactions by Fourier transform infrared and nuclear magnetic resonance spectroscopy. Besides, the unfathomed molecular mechanism of drug−polymer interplay is discerned at the air−water interface using sum-frequency generation spectroscopy to correlate the interfacial hydrogen bonding properties in bulk water. Surprisingly, all studies disseminate HPMC E15 and Soluplus as effective PIs of RFX.

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“…To obtain structural insights into the DAS-HA, DAS-HEA, and DAS-OA solvates, we extensively tried to grow the single crystals using various crystallization techniques, but our trials were unsuccessful in obtaining mountable single crystals; hence, we used orthogonal techniques to confirm solvate formation. To provide structural confirmation of the solvates unambiguously, we used several orthogonal techniques such as HSM, 47 1 H NMR, and temperature-cycled PXRD studies. All DAS fatty acid solvates show the final endothermic event in the DSC thermogram from 279.10 to 284.19 °C ( Figures 6 a, 8 a, and 10 a).…”

Section: Resultsmentioning

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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Hot stage microscopy and its applications in pharmaceutical characterization

Cited by 37 publications

References 50 publications

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

Elucidating the Molecular Mechanism of Drug–Polymer Interplay in a Polymeric Supersaturated System of Rifaximin

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

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