title: Eudragit® RL as a stabilizer for supersaturation and a substrate for nanocrystal formation.
abstract: In order to optimize supersaturation levels and avoid early drug precipitation, Eudragit® RL was tested as a carrier in solid dispersions, either alone or in combination with a hydrophilic polymer (PVP K25). In vitro dissolution performance of the spray dried solid dispersions was tested. The phase behavior of the produced solid dispersions was analyzed as well as dissolution precipitates. In case of weak acid model compounds (indomethacin and naproxen), the incorporation of Eudragit® RL resulted in a prolongation of supersaturation. A combination of PVP and Eudragit® RL led to high and stable drug concentrations. Eudragit® RL was only suited as a carrier in combination with higher drug loadings. Phase behavior analysis of the produced solid dispersions showed that Eudragit® RL could form glass solutions, and precipitate analysis showed that these drug-polymer combinations remained amorphous after in vitro dissolution for 24h. Surprisingly, indomethacin and naproxen also formed nanocrystals in presence of Eudragit® RL. These nanocrystals were formed by a dynamic interplay of dissolution, sorption and desorption. A charge interaction between anionic drugs and a cationic polymer provided a high driving force for sorption, which was necessary for nanocrystal formation and supersaturation stabilization.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.
authors.forename: Aswin
authors.initials: A
authors.lastname: Dereymaker
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cinghia
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium. Electronic address: guy.vandenmooter@kuleuven.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D002936:Cinnarizine / Q000737:chemistry; D003890:Desiccation; D004337:Drug Carriers; D004339:Drug Compounding; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009288:Naproxen / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D011108:Polymers; D002936:Cinnarizine; C058665:Eudragit RL; D009288:Naproxen; D007213:Indomethacin
keywords: Eudragit RL; Nanocrystals; Solid dispersions; Spray drying; Supersaturation; Thermal analysis; X-ray powder diffraction