title: Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion.
abstract: Amorphous solid dispersions have for many years been a focus in oral formulations, especially in combination with a hot-melt extrusion process. The present work targets a novel approach with a system based on a fatty acid, a polymer and an inorganic carrier. It was intended to adsorb the acidic lipid by specific molecular interactions onto the solid carrier to design disorder in the alkyl chains of the lipid. Such designed lipid microdomains (DLM) were created as a new microstructure to accommodate a compound in a solid dispersion. Vibrational spectroscopy, X-ray powder diffraction, atomic force microscopy as well as electron microscopic imaging were employed to study a system of stearic acid, hydroxypropylcellulose and aluminum magnesium silicate. β-carotene was used as a poorly water-soluble model substance that is difficult to formulate with conventional solid dispersion formulations. The results indicated that the targeted molecular excipient interactions indeed led to DLMs for specific compositions. The different methods provided complementary aspects and important insights into the created microstructure. The novel delivery system appeared to be especially promising for the formulation of oral compounds that exhibit both high crystal energy and lipophilicity.
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: Swiss Nanoscience Institute, Nanotech Service Lab, Klingelbergstrasse 82, 4056 Basel, Switzerland.
authors.forename: Monica
authors.initials: M
authors.lastname: Schönenberger
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: D017607:Aluminum Compounds / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D017616:Magnesium Compounds / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D018625:Microscopy, Atomic Force; D011108:Polymers / Q000737:chemistry*; D017640:Silicates / Q000737:chemistry; D012995:Solubility; D013057:Spectrum Analysis / Q000379:methods; D013229:Stearic Acids / Q000737:chemistry; D014732:Vibration; D014961:X-Ray Diffraction; D019207:beta Carotene / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D017607:Aluminum Compounds; D005079:Excipients; D008055:Lipids; D017616:Magnesium Compounds; D011108:Polymers; D017640:Silicates; D013229:Stearic Acids; D019207:beta Carotene; C031183:stearic acid; C033065:aluminum magnesium silicate; D002482:Cellulose; C008079:hydroxypropylcellulose
keywords: Acidic lipid; Designed lipid microdomains; Hot-melt extrusion; Inorganic carrier; Interactions