Multifractal Characterization of Pharmaceutical Hot-Melt Extrudates



Multifractal geometry has become a powerful tool to describe complex structures in many fields. Our first aim was to combine imaging and multifractal analysis to better understand the microstructure of pharmaceutical extrudates. A second objective was to study erosion/dispersion behavior of the formulations because it would condition release of any drug.


Different formulations containing a lipid, a polymer and different silica based inorganic carriers were produced by hot-melt extrusion at various screw speeds. Multifractal analysis was based on scanning electron microscopy/energy dispersive X-Ray spectroscopy images. This microstructural analysis was complemented with dynamic optical imaging of formulation erosion/dispersion behavior.


Multifractal analysis indicated that inorganic carrier type and concentration as well as the screw speed affected the microstructure of the extrudates. The aqueous erosion/dispersion study showed that only the type and concentration of inorganic carrier were important.


The use of microstructural and dispersion analysis appeared to be complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.

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Analysis of variance


Electron dispersive X-Ray spectroscopy


Hot-melt extrusion


Polyvinylpyrrolidone-vinyl acetate


Scanning electron microscopy




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Correspondence to Martin Kuentz.



SEM pictures of the used adsorbent powders are presented in this Appendix A to illustrate their physical variety.

Fig. 10

SEM pictures of fumed Aerosil 300 (a), and Aerosil R 972 (b). Aerosil fumed silicates are very fine powders composed of aggregated and agglomerated primary particles. Primary particles could not be identified due to their very small size (< 50 nm) (30).

Fig. 11

SEM pictures of Aeroperl 300 (a, d), Florite R (b, e), and Neusilin US2 (c, f). Aeroperl 300 spherical granules have a rather smooth surface. Florite R particles exhibit irregular shape while the pore structure can be viewed as petaloid. Finally, the spherical Neusilin US2 particles display some porosity on their surface compared to Aeroperl 300.

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Adler, C., Teleki, A. & Kuentz, M. Multifractal Characterization of Pharmaceutical Hot-Melt Extrudates. Pharm Res 34, 321–332 (2017).

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  • dispersion
  • hot-melt extrusion
  • inorganic carrier
  • multifractal
  • scanning electron microscopy