title: Understanding the performance of melt-extruded poly(ethylene oxide)-bicalutamide solid dispersions: characterisation of microstructural properties using thermal, spectroscopic and drug release methods.
abstract: In this article, we have prepared hot-melt-extruded solid dispersions of bicalutamide (BL) using poly(ethylene oxide) (PEO) as a matrix platform. Prior to preparation, miscibility of PEO and BL was assessed using differential scanning calorimetry (DSC). The onset of BL melting was significantly depressed in the presence of PEO, and using Flory-Huggins (FH) theory, we identified a negative value of -3.4, confirming miscibility. Additionally, using FH lattice theory, we estimated the Gibbs free energy of mixing which was shown to be negative, passing through a minimum at a polymer fraction of 0.55. Using these data, solid dispersions at drug-to-polymer ratios of 1:10, 2:10 and 3:10 were prepared via hot-melt extrusion. Using a combination of DSC, powder X-ray diffractometry and scanning electron microscopy, amorphous dispersions of BL were confirmed at the lower two drug loadings. At the 3:10 BL to PEO ratio, crystalline BL was detected. The percent crystallinity of PEO was reduced by approximately 10% in all formulations following extrusion. The increased amorphous content within PEO following extrusion accommodated amorphous BL at drug to polymer loadings up to 2:10; however, the increased amorphous domains with PEO following extrusion were not sufficient to fully accommodate BL at drug-to-polymer ratios of 3:10.
authors: The Drug Delivery and Biomaterials Group, School of Pharmacy, Medical Biology Centre, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
authors: Osama A
authors: OA
authors: Abu-Diak
authors: David S
authors: DS
authors: Jones
authors: Gavin P
authors: GP
authors: Andrews
mesh_terms: D000813:Anilides / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D005615:Freezing; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009570:Nitriles / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013059:Spectrum Analysis, Raman / Q000379:methods; D014105:Tosyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000813:Anilides; D009570:Nitriles; D004364:Pharmaceutical Preparations; D011108:Polymers; D014105:Tosyl Compounds; D011092:Polyethylene Glycols; C053541:bicalutamide