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. 2023 Feb 10;15(2):603.
doi: 10.3390/pharmaceutics15020603.

Screening of Fenofibrate-Simvastatin Solid Dispersions in the Development of Fixed-Dose Formulations for the Treatment of Lipid Disorders

Agata Górniak  1 , Hanna Czapor-Irzabek  1 , Adrianna Złocińska  1 , Agnieszka Gawin-Mikołajewicz  2 , Bożena Karolewicz  2
Affiliations

Screening of Fenofibrate-Simvastatin Solid Dispersions in the Development of Fixed-Dose Formulations for the Treatment of Lipid Disorders

Agata Górniak et al. Pharmaceutics. .

Abstract

The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.

Keywords: dissolution improvement; dyslipidemia; eutectic; fenofibrate; fixed-dose combination; simvastatin; solid dispersion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of (a) fenofibrate and (b) simvastatin.
Figure 2
Figure 2
DSC curves of FEN, SIM, and FEN-SIM SDs containing 10–80 FEN wt% obtained at the heating rate of 5 °C/min in a temperature range from 25 to 150 °C.
Figure 3
Figure 3
DSC curves of FEN-SIM SDs containing 90–97 FEN wt% obtained at the heating rate of 0.5 °C/min in a temperature range from 60 to 90 °C.
Figure 4
Figure 4
Tamman’s triangle of eutectic reaction enthalpy ΔH at 74.8 °C versus SIM wt%.
Figure 5
Figure 5
Temperature–composition phase diagram for the FEN-SIM binary system: (L) liquid, (L + SIM) liquid + solid SIM, (FEN + L) solid FEN + liquid, (E) eutectic point, (FEN + SIM) solid FEN + solid SIM.
Figure 6
Figure 6
XRPD patterns of FEN, SIM, and FEN-SIM SDs.
Figure 7
Figure 7
FTIR spectra of pure FEN, SIM, and FEN-SIM binary SDs.
Figure 8
Figure 8
SEM images of raw FEN and SIM and representative FEN-SIM samples.
Figure 9
Figure 9
The dissolution profile of FEN released from FEN-SIM samples on IDR studies.
Figure 10
Figure 10
The dissolution profile of SIM released from FEN-SIM samples on IDR studies.
Figure 11
Figure 11
The dissolution profile of FEN released from FEN-SIM samples by the paddle method.
Figure 12
Figure 12
The dissolution profile of SIM released from FEN-SIM samples by the paddle method.
Figure 13
Figure 13
The contact angle of water on the FEN and SIM powder surfaces.
Figure 14
Figure 14
The contact angle of water on the powder surfaces of SDs tested with the paddle method.
See this image and copyright information in PMC

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