title: Multifractal and mechanical analysis of amorphous solid dispersions.
abstract: The formulation of lipophilic and hydrophobic compounds is a challenge for the pharmaceutical industry and it requires the development of complex formulations. Our first aim was to investigate hot-melt extrudate microstructures by means of multifractal analysis using scanning electron microscopy imaging. Since the microstructure can affect solid dosage form performance such as mechanical properties, a second objective was to study the influence of the type of adsorbent and of the presence of an amorphous compound on extrudate hardness. β-Carotene (BC) was chosen as poorly water-soluble model compound. Formulations containing a polymer, a lipid and two different silica based inorganic carriers were produced by hot-melt extrusion. Based on scanning electron microscopy/energy dispersive X-ray spectroscopy, the obtained images were analyzed using multifractal formalism. The breaking force of the strands was assessed by a three point bending test. Multifractal analysis and three point bending results showed that the nature of interparticle interactions in the inorganic carrier as well as the presence of amorphous BC had an influence on the microstructure and thus on the mechanical performance. The use of multifractal analysis and the study of the mechanical properties were complementary to better characterize and understand complex formulations obtained by hot-melt extrusion.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharmaceutical Technology, Gründenstrasse 40, 4132 Muttenz, Switzerland; University of Basel, Institute of Pharmaceutical Technology, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Adler
authors.affiliation: DSM Nutritional Products Ltd., R&D Center Formulation & Application, P. O. Box 2676, 4002 Basel, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Teleki
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, Institute of Pharmaceutical Technology, Gründenstrasse 40, 4132 Muttenz, Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding; D008855:Microscopy, Electron, Scanning; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D033362:Powder Diffraction; D011409:Propylene Glycols / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D013052:Spectrometry, X-Ray Emission; D013059:Spectrum Analysis, Raman; D013535:Suspensions; D014961:X-Ray Diffraction; D019207:beta Carotene / Q000737:chemistry*
chemical_list: D011409:Propylene Glycols; D013535:Suspensions; C549547:vinylacetate-vinylpyrrolidone copolymer; D019207:beta Carotene; D012822:Silicon Dioxide; D011205:Povidone
keywords: Hot-melt extrusion; Inorganic carrier; Mechanical properties; Multifractal; Scanning electron microscopy; Solid dispersion