scholarly journals Structural Characterisation of Amorphous Solid Dispersions via Metropolis Matrix Factorisation of Pair Distribution Function Data

2019 ◽  
Author(s):  
Harry Geddes ◽  
Helen Blade ◽  
James McCabe ◽  
Leslie P. Hughes ◽  
Andrew Goodwin
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Distribution Functions ◽  
Atomistic Simulations ◽  
Amorphous Solid Dispersions ◽  
Structural Characterisation ◽  
Amorphous Pharmaceuticals ◽  
Amorphous Drug ◽  
Pair Distribution Functions ◽  
Matrix Factorisation

We measure the X-ray pair distribution functions (PDFs) of a series of felodipine:copovidone amorphous solid dispersions. Using a newly-developed Metropolis Matrix Factorisation (MMF) algorithm we extract from these data the PDF of the amorphous felodipine component in isolation. Our MMF analysis allows quantification of the degree of drug crystallinity in each sample, and structural characterisation of the amorphous drug <i>via</i>its PDF. Comparison with atomistic simulations reveals that the (in)accessibility of conformational rotamers distinguishes amorphous and crystalline felodipine, in turn suggesting design routes for stabilising the amorphous form. We discuss the conceptual importance of our results in the context of characterising not only amorphous pharmaceuticals, but complex mixtures in general.

scholarly journals Structural Characterisation of Amorphous Solid Dispersions via Metropolis Matrix Factorisation of Pair Distribution Function Data

2019 ◽  
Author(s):  
Harry Geddes ◽  
Helen Blade ◽  
James McCabe ◽  
Leslie P. Hughes ◽  
Andrew Goodwin
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Distribution Functions ◽  
Atomistic Simulations ◽  
Amorphous Solid Dispersions ◽  
Structural Characterisation ◽  
Amorphous Pharmaceuticals ◽  
Amorphous Drug ◽  
Pair Distribution Functions ◽  
Matrix Factorisation

We measure the X-ray pair distribution functions (PDFs) of a series of felodipine:copovidone amorphous solid dispersions. Using a newly-developed Metropolis Matrix Factorisation (MMF) algorithm we extract from these data the PDF of the amorphous felodipine component in isolation. Our MMF analysis allows quantification of the degree of drug crystallinity in each sample, and structural characterisation of the amorphous drug <i>via</i>its PDF. Comparison with atomistic simulations reveals that the (in)accessibility of conformational rotamers distinguishes amorphous and crystalline felodipine, in turn suggesting design routes for stabilising the amorphous form. We discuss the conceptual importance of our results in the context of characterising not only amorphous pharmaceuticals, but complex mixtures in general.

scholarly journals Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data

2019 ◽  
Vol 55 (89) ◽  
pp. 13346-13349 ◽  
Author(s):  
Harry S. Geddes ◽  
Helen Blade ◽  
James F. McCabe ◽  
Leslie P. Hughes ◽  
Andrew L. Goodwin
Keyword(s):  
Distribution Function ◽  
Pair Distribution Function ◽  
Solid Dispersions ◽  
Complex Mixture ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions ◽  
Total Scattering ◽  
Structural Characterisation ◽  
Function Data ◽  
Matrix Factorisation

We use total scattering and non-negative matrix factorisation to characterise the structure of an amorphous pharmaceutical in a complex mixture.

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
Author(s):  
Joanna Szafraniec-Szczęsny ◽  
Agata Antosik-Rogóż ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
Ewa Szefer ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Active Pharmaceutical Ingredient ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
High Propensity ◽  
Poorly Soluble ◽  
Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

scholarly journals XRPD to Characterize Disordered and Amorphous Pharmaceutical Samples

2014 ◽  
Vol 70 (a1) ◽  
pp. C1558-C1558
Author(s):  
Ann Newman
Keyword(s):  
Disordered Systems ◽  
Amorphous Materials ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Rietveld Analysis ◽  
Distribution Functions ◽  
Pharmaceutical Samples ◽  
Data Pair ◽  
Crystalline Forms ◽  
Pair Distribution Functions

X-ray powder diffraction is commonly used to characterize pharmaceutical samples to identify crystalline forms as well as differentiate crystalline vs amorphous materials. Using XRPD for amorphous materials is usually limited to determining if the materials are fully amorphous or a mixture of crystalline and amorphous materials. Changes in the amorphous halos under various conditions (grinding, drying, water sorption, etc) are usually not investigated, but can give information on the system. This presentation will discuss other uses of XRPD in characterizing amorphous and disordered systems, including amorphous solid dispersions. Patterns involving nanocrystalline, amorphous, and defected samples will be presented and examples on using various methods to obtain further information from the data (pair distribution functions, pure curve resolution methods, diffuse scattering, and Rietveld analysis) will be included.

Development of novel darunavir amorphous solid dispersions with mesoporous carriers

2021 ◽  
Vol 159 ◽  
pp. 105700
Author(s):  
Sergey A. Zolotov ◽  
Natalia B. Demina ◽  
Anna S. Zolotova ◽  
Natalia V. Shevlyagina ◽  
Grigorii A. Buzanov ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

Effect of Carrier Type and Tween® 80 Concentration on the Release of Silymarin from Amorphous Solid Dispersions

2021 ◽  
pp. 102416
Author(s):  
Valentyn Mohylyuk ◽  
Thomas Pauly ◽  
Oleksandr Dobrovolnyi ◽  
Nathan Scott ◽  
David S. Jones ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

scholarly journals Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 90
Author(s):  
Eun-Sol Ha ◽  
Du Hyung Choi ◽  
In-hwan Baek ◽  
Heejun Park ◽  
Min-Soo Kim
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Pharmaceutical Products ◽  
In Vitro Dissolution ◽  
Dependent Manner ◽  
Amorphous Solid Dispersions ◽  
Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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