title: Drug structural features affect drug delivery from hyperbranched polyesteramide hot melt extrudates.
abstract: The aim of this study was firstly to evaluate the utility of Hybrane S1200 as a hot melt extrusion (HME) carrier to prepare instant-release multiparticulate systems for very poorly-soluble drugs such as ketoconazole or nifedipine. Hybrane S1200 allows an easy extrusion of its drug mixtures at a relatively low temperature, not higher than 90°C, and with no need of any additional aid. Extrudates containing 10% of nifedipine or ketoconazole form monophasic systems. Nifedipine extrudate shows no drug release in drug dissolution rate tests while ketoconazole extrudate release reaches only 60% of drug content. Additionally, a turbidity in the dissolution medium due to the formation of a kind of polymer vesicles (ranging 3-0.2μm in size) is observed. These facts could suggest a chemical interaction between the polymer and both drugs, triggered by the HME process. Both nifedipine and ketoconazole share characteristic acid-base profiles that could facilitate a degradation processes within the polymer, thus modifying Hybrane's water-solubility and polar nature. Such modified polymer structure, when in aqueous medium, forms the aforementioned stable vesicles that may encapsulate the drugs, thus making its delivery difficult or even preventing it.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Institute of Industrial Pharmacy, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Raviña-Eirin
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS) and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Jhonny
authors.initials: J
authors.lastname: Azuaje
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS) and Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Eddy
authors.initials: E
authors.lastname: Sotelo
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Institute of Industrial Pharmacy, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Gomez-Amoza
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Institute of Industrial Pharmacy, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain. Electronic address: ramon.martinez@usc.es.
authors.forename: Ramon
authors.initials: R
authors.lastname: Martinez-Pacheco
mesh_terms: D000577:Amides / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D006358:Hot Temperature; D007654:Ketoconazole / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012995:Solubility
chemical_list: D000577:Amides; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011091:Polyesters; D011108:Polymers; D009543:Nifedipine; D007654:Ketoconazole
keywords: Chemical interaction; Hot-melt extrusion; Hybrane S1200; Hyperbranched polymer; Ketoconazole; Nifedipine