title: In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids.
abstract: Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5 s), fast dissolution (97% in 10 min) and optimum tensile strength (4.9 N/cm2). The results of in vivo data indicated high bioavailability (144 ng h/mL) and maximum plasma concentration (14.2 ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Beni Suef University , Beni Suef , Egypt.
authors.forename: Eman Magdy
authors.initials: EM
authors.lastname: Maher
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Beni Suef University , Beni Suef , Egypt.|b Department of Pharmaceutics , Faculty of Pharmacy, Taif University , Taif , Saudi Arabia , and.
authors.forename: Ahmed Mahmoud Abdelhaleem
authors.initials: AM
authors.lastname: Ali
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Beni Suef University , Beni Suef , Egypt.
authors.forename: Heba Farouk
authors.initials: HF
authors.lastname: Salem
authors.affiliation: c Department of Pharmaceutics , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Ahmed Abdelbary
authors.initials: AA
authors.lastname: Abdelrahman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001569:Benzodiazepines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002264:Carboxylic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008855:Microscopy, Electron, Scanning / Q000379:methods; D000077152:Olanzapine; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013055:Spectrophotometry, Infrared / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D055815:Young Adult
chemical_list: D002264:Carboxylic Acids; D005079:Excipients; D004364:Pharmaceutical Preparations; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Amorphous; bioavailability; fast dissolving film; neural networks; olanzapine; pharmacokinetics; solid dispersion