title: Binary polymeric blends to microencapsulate nitroflurbiprofen: physicochemical and in silico studies.
abstract: Nitroflurbiprofen, NFP, a practically insoluble liquid drug, was microencapsulated in hydrophilic micromatrices made of poly(N-vinylpyrrolidone) (PVP), or polyaminomethacrylate (PAMA), or binary blends of polymers thereof. The PAMA/PVP miscibility was assessed both in the solid state (DSC and ATF-FTIR spectroscopy) and in solution by viscometric measurements. The in vitro NFP release test was carried out in over saturation condition to discriminate the increase of NFP apparent solubility (supersaturation degree, SD). Drug/polymer/polymer/water interactions were studied in silico by molecular dynamic (MD) simulations. PAMA and PVP resulted miscible only in aqueous solution. The release of NFP from microparticles occurred according to a non-monotonic pattern due to the formation of instable supersaturated systems and the drug separation in the dissolution medium. After 5 min, the SD was at least 3. The use of PVP/PAMA micromatrices reduced the instability of the supersaturated solutions. MD simulations evidenced that water molecules play a key role in the PAMA/PVP compatibilization process and in stabilization of NFP supersaturated systems by means of H-bond. The docking analyses here find a novel and successful application to predict the different ability of a drug to interact with polymeric blends in solution.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica P. Pratesi, Università degli Studi di Milano, Milan, Italy. francesco.cilurzo@unimi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Cilurzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Paola
authors.initials: P
authors.lastname: Minghetti
authors.forename: Luisa
authors.initials: L
authors.lastname: Montanari
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009010:Monte Carlo Method; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D044366:Transition Temperature; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D000179:Acrylates; D016861:Cyclooxygenase Inhibitors; D004337:Drug Carriers; C477020:Eudragit E100; D011108:Polymers; D014867:Water; C095631:nitroflurbiprofen; D005480:Flurbiprofen; D011205:Povidone