Pair distribution function X‐ray analysis explains dissolution characteristics of felodipine melt extrusion products

Nollenberger, Kathrin; Gryczke, Andreas; Meier, Ch.; Dressman, Jennifer B.; Schmidt, Martin; Brühne, Stefan

doi:10.1002/jps.21534

Cited by 48 publications

(34 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Raman spectroscopy has been extensively applied in pharmaceutical research for both qualitative and quantitative purposes, and it has been successfully utilized to determine hydrogen bonding 64-68 . Nollenberger et al reported that FEL has a characteristic N-H stretch peak at 3375 cm −1 as well as a characteristic peak at 1639 cm −1 owing to the free carbonyl stretching 67 . Although the N-H stretch peak in FEL was not obvious in the Raman study here, attributed to the higher intensity of other molecular vibrations (Figure 8a), a Raman peak shift was clearly observed in the range of 1200–1700 cm −1 , which is an indication of potential intermolecular interaction (Figure 8b).…”

Section: Resultsmentioning

confidence: 99%

Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

Cuellar

Hammer

et al. 2015

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

The aim of the current study is to develop amorphous solid dispersion via hot melt extrusion technology to improve the solubility of a water-insoluble compound, felodipine. The solubility was dramatically increased by preparation of amorphous solid dispersions via hot-melt extrusion with an amphiphilic polymer, Soluplus®. Felodipine was found to be miscible with Soluplus® by calculating the solubility parameters. The solubility of felodipine within Soluplus® was determined to be in the range of 6.2–9.9% (w/w). Various techniques were applied to characterize the solid-state properties of the amorphous solid dispersions. These included Fourier Transform Infrared Spectroscopy and Raman spectroscopy to detect the formation of hydrogen bonding between the drug and the polymer. Scanning electron microscopy was performed to study the morphology of the solid dispersions. Among all the hot-melt extrudates, felodipine was found to be molecularly dispersed within the polymer matrix for the extrudates containing 10% drug, while few s mall crystals were detected in the 30 and 50% extrudates. In conclusion, solubility of felodipine was enhanced while a homogeneous solid dispersion was achieved for 10% drug loading.

show abstract

Section: Resultsmentioning

confidence: 99%

Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

Cuellar

Hammer

et al. 2015

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

show abstract

“…In the material science community the PDF technique has been used for several decades (101-105) and has more recently been applied by the pharmaceutical community to study short-and long-range order amorphous glassy materials (106)(107)(108)(109)(110)(111). It has been used in studies to investigate crystalline defects, help in the crystal structure determination (106,107,110), characterization of polymer/drug systems (111)(112)(113) and the use of multivariate data analysis has alleviated the interpretation of PDF (108,111). It could be a possible route to gain a deeper insight into the degree of disorder in a milled sample.…”

Section: Atomic Pairwise Distributionmentioning

confidence: 99%

“…Depending on the instrument type, measuring parameters and experimental conditions, there are several methodologies that can be employed to determine the latter. Among them are conventional DSC, modulated temperature DSC (MTDSC) and hyper-or high-speed DSC (HSDSC) (113). Conventional DSC is based on a linear heating rate.…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

Methods of amorphization and investigation of the amorphous state

Einfalt¹,

Planinšek²,

Hrovat³

2013

Acta Pharmaceutica

114

View full text Add to dashboard Cite

.g., polymorphs) provides pharmaceutical scientists with an opportunity to select the preferred form of the material to be used in a formulation. This is very useful since critical properties, such as particle morphology and dissolution properties, are frequently different in the different physical forms of a material. The amorphous form of pharmacologically active materials has received considerable attention because, in theory, it represents the most energetic solid state of a material, and should thus provide the biggest advantages in terms of dissolution rate and bioavailability (1). However, the amorphous form also shows various disadvantages, such as lower physical stability compared to crystals.The structure of an amorphous solid is usually described as possessing a crystal--like short-range molecular arrangement, but lacking a long-range order. As illustrated by Fig. 1, the immediate environment of a molecule (m) in an amorphous solid may not differ significantly from that in a crystal (e.g., similar number of and distance to nearest neighbors), but an amorphous solid lacks any long-range transational-orientational symmetry that characterizes a crystal (1). However, this is only true when we are dealing The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid--state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.

show abstract

“…Eudragit ® S100 is soluble in the colonic fluid at pH above 7.0. This polymer has a reported T g of 172 • C (Schilling et al, 2010) and a maximum processing temperature of 186 • C (Nollenberger et al, 2009). In order to facilitate the melt processing of Eudragit ® S100 triethyl citrate (TEC) (Sigma-Aldrich) was used as a plasticizer.…”

Section: Methodsmentioning

confidence: 99%

Drug release characteristics from nanoclay hybrids and their dispersions in organic polymers

Xanthos

2011

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Pair distribution function X‐ray analysis explains dissolution characteristics of felodipine melt extrusion products

Cited by 48 publications

References 28 publications

Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

Methods of amorphization and investigation of the amorphous state

Drug release characteristics from nanoclay hybrids and their dispersions in organic polymers

Contact Info

Product

Resources

About