Understanding the solid-state forms of fenofibrate – A spectroscopic and computational study

Heinz, Andrea; Gordon, Keith C.; McGoverin, Cushla; Rades, Thomas; Strachan, Clare J.

doi:10.1016/j.ejpb.2008.05.030

Cited by 93 publications

(90 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The melting points of the FNT formulations were very similar, and the value was approximately 80 C, which matched to the melting point of the crystalline FNT form I reported by Heinz et al (2009), demonstrating that crystalline FNT form I were existed in the FNT formulations.…”

Section: Differential Scanning Calorimetrysupporting

confidence: 64%

Pharmaceutical and pharmacokinetic characteristics of different types of fenofibrate nanocrystals prepared by different bottom-up approaches

et al. 2013

View full text Add to dashboard Cite

Low dissolution rate of a poorly water soluble drug often leads to low and variable oral bioavailability. Formulating drugs as nanocrystals can help to overcome these problems by increasing the solubility and dissolution velocity. But different preparation approaches may result in different nanocrystals with different characteristics. In this study, three types of fenofibrate nanocrystals (FNT-NCs) were prepared by bottom-up methods, antisolvent and thermal precipitation under different conditions. These FNT-NCs were characterized by scanning electron micrography, dissolution testing, differential scanning calorimetry and powder X-ray diffractometry. A significant increase of dissolution rate was observed in the drug nanocrystals compared to the crude FNT powder (from 20% to 80% in 5 min). The crystallinity of the FNT-NCs prepared by antisolvent precipitation increased slightly, while that by thermal precipitation decreased. The oral bioavailability of two types of FNT-NCs prepared by antisolvent precipitation in rats increased notably compared to that of the crude powder (5.5-folds and 5.0-folds, respectively). However, the oral absorption of FNT-NCs prepared by thermal precipitation did not increase, although its dissolution rate was higher than that of the crude powder. In conclusion, different bottom-up methods produce different FNT-NCs with different crystallinity, which results in different oral bioavailability. Namely, a careful study and rational choice on preparation approaches are significant for the nanocrystal techniques.

show abstract

Section: Differential Scanning Calorimetrysupporting

confidence: 64%

Pharmaceutical and pharmacokinetic characteristics of different types of fenofibrate nanocrystals prepared by different bottom-up approaches

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Loadings and (c) scores plots generated by principal component analysis from the Raman spectra obtained upon heating amorphous fenofibrate between -180 and 90 C. Loadings are offset for clarity. Reprinted from Heinz et al [145] with permission from Elsevier.…”

Section: Fundingmentioning

confidence: 99%

“…In-situ FTIR and Raman microscopy Carbamazepine [144] Solid-solid recrystallisation of amorphous carbamazepine to carbamazepine form III Heating In-situ TPS Fenofibrate [145] Solid-solid recrystallisation of amorphous fenofibrate via metastable form II to form I Heating In-situ Raman spectroscopy Carbamazepine, indometacin [146] Solution-mediated recrystallisation of amorphous indometacin and carbamazepine …”

Section: Different Relative Humiditiesmentioning

confidence: 99%

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

View full text Add to dashboard Cite

Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni-or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis.

show abstract

“…Fenofibrate was characterized by a single sharp melting endothermic peak at 81.5°C (∆H = 80.57 J/g) during differential scanning calorimetry analysis, and various diffraction peaks due to the fenofibrate crystalline (form I) structure were observed at 12°, 14.5°, 16.2°, 16.8°, and 22.4° in the PXRD analysis, which corresponds to the known melting endothermic peak and powder diffraction patterns for pure fenofibrate. 24,25 In the case of Neusilin UFL2, neither an endothermic peak of differential scanning calorimetry nor diffraction peaks from PXRD patterns were observed because of its amorphous structure. Table 3 and Figure 4 illustrate decreasing crystallinity corresponding to an increasing Neusilin UFL2 ratio and the change to the amorphous form in the case of SC3 and SC4.…”

Section: Crystallinity Evaluationmentioning

confidence: 99%

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

Ho¹,

Cho²,

Kim³

et al. 2012

IJN

View full text Add to dashboard Cite

Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO 2 . Methods: Fenofibrate was loaded onto Neusilin ® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO 2 . For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated. Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO 2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO 2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate. Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO 2 for improving the bioavailability of fenofibrate.

show abstract

Understanding the solid-state forms of fenofibrate – A spectroscopic and computational study

Cited by 93 publications

References 32 publications

Pharmaceutical and pharmacokinetic characteristics of different types of fenofibrate nanocrystals prepared by different bottom-up approaches

Pharmaceutical and pharmacokinetic characteristics of different types of fenofibrate nanocrystals prepared by different bottom-up approaches

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

Contact Info

Product

Resources

About