The determination of crystal structures of active pharmaceutical ingredients from X-ray powder diffraction data: a brief, practical introduction, with fexofenadine hydrochloride as example

Brüning, Jürgen; Schmidt, Martin

doi:10.1111/jphp.12374

Cited by 25 publications

(17 citation statements)

References 45 publications

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“…Expectedly, both the binary physical mixture and cryomilled sample present identical sharp peaks as crystalline nifedipine, suggesting that upon processing, the majority of nifedipine still retain their crystallinity. However, the corresponding diffraction peaks from the cryomilled sample become broad and blurry, signifying that high energy cryogenic milling may lead to a significant decrease of crystal size . Interestingly, the extrudate prepared below the critical temperature (150 °C) also displays a pronounced combination of both characteristic peaks of crystal nifedipine and amorphous halos suggesting the existence of a certain amount of API crystallinity, which was also confirmed by previous imaging characterizations.…”

Section: Results and Discussionsupporting

confidence: 75%

“…However, the corresponding diffraction peaks from the cryomilled sample become broad and blurry, signifying that high energy cryogenic milling may lead to a significant decrease of crystal size. 35 Interestingly, the extrudate prepared below the critical temperature (150 °C) also displays a pronounced combination of both characteristic peaks of crystal nifedipine and amorphous halos suggesting the existence of a certain amount of API crystallinity, which was also confirmed by previous imaging characterizations. Conversely, in the case of extrudate prepared at the critical temperature (160 °C), only trace amount of diffraction peaks associated with the crystalline drugs are observed, representing the existence of residual API crystals in extrudate owing to the wide particle size distribution of asreceived API and insufficient residence time during HME processing.…”

Section: Resultssupporting

confidence: 73%

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Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone–Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME)

Yang

Zhang

et al. 2016

Mol. Pharmaceutics

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The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation and decomposition of thermally sensitive components. Herein, the rheological properties of a physical mixture of polymer and an active pharmaceutical ingredient (API) were utilized to guide the selection of appropriate HME processing temperature. In the currently studied copovidone-nifedipine system, a critical temperature, which is substantially lower (∼13 °C) than the melting point of crystalline API, was captured during a temperature ramp examination and regarded as the critical point at which the API could molecularly dissolve into the polymer. Based on the identification of this critical point, various solid dispersions were prepared by HME processing below, at, and above the critical temperature (both below and above the melting temperature (T) of crystalline API). In addition, the resultant extrudates along with two control solid dispersions prepared by physical mixing and cryogenic milling were assessed by X-ray diffraction, differential scanning calorimetry, hot stage microscopy, rheology, and solid-state NMR. Physicochemical properties of resultant solid dispersions indicated that the identified critical temperature is sufficient for the polymer-API system to reach a molecular-level mixing, manifested by the transparent and smooth appearance of extrudates, the absence of API crystalline diffraction and melting peaks, dramatically decreased rheological properties, and significantly improved polymer-API miscibility. Once the critical temperature has been achieved, further raising the processing temperature only results in limited improvement of API dispersion, reflected by slightly reduced storage modulus and complex viscosity and limited improvement in miscibility.

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Section: Results and Discussionsupporting

confidence: 75%

Section: Resultssupporting

confidence: 73%

Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone–Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME)

Yang

Zhang

et al. 2016

Mol. Pharmaceutics

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“…The algorithm of metal-organic nanomaterials quality control methods development was worked out; algorithm primarily includes study of the structure of nanomaterials, for example, by X-ray crystallography method [10][11][12].…”

Section: Resultsmentioning

confidence: 99%

Study of Metal-Organic Nanomaterials Structure by X-ray Crystallography Analysis as the Basis for the Development of Quality Control Methods

Bilous¹,

Dmytriv²,

Didikin³

et al. 2015

JPP

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Abstract:The aim of the work is to study the structure of antimicrobial agents metronidazole and levofloxacin and their nanocompositions with silver nanoparticles obtained by by electron-ray nanotechnology method, and to demonstrate the necessity of x-ray crystalography analysis for developing quality control methods of metal-organic nanomaterials. Structure of antimicrobial agents and their nanocompositions was investigated on automatic powder diffractometer STOE STADI P (MoKα-radiation stepping removal method, 2 ° ≤ 2θ ≤ 30 °, step scan −0.02 °, scanning at one point −5-10 c). For identification of nanocompositions the UV spectrophotometry metod was used.

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“…PXRD shown in Figure 3A was used to characterize the two solid forms of FXD. The characteristic peaks of Form I were at 2θ = 5.9 • , 7.5 [28,29]. The FTIR spectra of two solid forms were presented in Figure 3B.…”

Section: Solid State Characterization Of Polymorphsmentioning

confidence: 99%

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

Zhao

et al. 2021

Pharmaceutics

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The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

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The determination of crystal structures of active pharmaceutical ingredients from X-ray powder diffraction data: a brief, practical introduction, with fexofenadine hydrochloride as example

Abstract: Crystal structures of API can be determined from X-ray powder diffraction data with good reliability. Fexofenadine exhibits only one polymorphic form, which is stabilised in the crystal by strong hydrogen bonds of the type (+)N-H···Cl(-), O-H···Cl(-), and between COOH groups.

Cited by 25 publications

References 45 publications

Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone–Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME)

Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone–Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME)

Study of Metal-Organic Nanomaterials Structure by X-ray Crystallography Analysis as the Basis for the Development of Quality Control Methods

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

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