title: Solid microcrystalline dispersion films as a new strategy to improve the dissolution rate of poorly water soluble drugs: A case study using olanzapine.
abstract: In this study, we evaluate the dissolution rate enhancement of solid microcrystalline dispersion (SMD) films of olanzapine (OLZ) formulated with four water-soluble polymers namely poly(N-vinylpyrrolidone) (PVP), poloxamer 188 (P188), poloxamer 407 (P407) and Soluplus(®) (SLP). Prepared formulations were characterised to determine particle size, morphology, hydrogen bonding interactions, thermal characteristics as well as in vitro dissolution studies conducted under sink conditions (pH 6.8). Particle size of OLZ in all formulations ranged between 42 and 58μm. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Hot-Stage Microscopy (HSM) studies confirmed OLZ was well maintained in its crystalline state during the formulation process. In vitro dissolution studies showed immediate drug release from all formulation when compared to the drug alone. The greatest increase in in vitro dissolution rate was observed in formulations containing P188 most likely due to its enhanced hydrophilic and surfactant properties compared to the other agents used. Overall, this study successfully generated OLZ loaded SMD films with improved in vitro dissolution rates which is highly likely to result in improved oral bioavailability in vivo.
authors.affiliation: Faculty of Pharmacy, University of Study of Palermo, Palermo, Italy. Electronic address: laly0692@hotmail.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Modica de Mohac
authors.affiliation: University College London, School of Pharmacy, Department of Pharmaceutics, 29-39 Brunswick Square, London, WC1N 1AX, UK. Electronic address: m.pina@ucl.ac.uk.
authors.forename: Maria
authors.initials: M
authors.lastname: de Fátima Pina
authors.affiliation: University College London, School of Pharmacy, Department of Pharmaceutics, 29-39 Brunswick Square, London, WC1N 1AX, UK. Electronic address: b.raimi-abraham@ucl.ac.uk.
authors.forename: Bahijja Tolulope
authors.initials: BT
authors.lastname: Raimi-Abraham
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry* / Q000493:pharmacokinetics; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D006860:Hydrogen Bonding; D000077152:Olanzapine; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry*; D012995:Solubility
chemical_list: D011145:Polyvinyls; D011760:Pyrrolidinones; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D020442:Poloxamer; D001569:Benzodiazepines; D011092:Polyethylene Glycols; C042670:N-vinyl-2-pyrrolidinone; D000077152:Olanzapine
keywords: Crystalline; Olanzapine; Olanzapine (PubChem CID: 4585); PVP; Pharmaceutical film; Poloxamer 188 (PubChem CID: 24751); Poloxamer 407 (PubChem CID: 24751); Poly(N-vinylpyrrolidone) (PubChem CID: 6917); Polymer; Solid microcrystalline dispersion