title: A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance.
abstract: The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying.
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Khattawi
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK; Aston Research Centre for Children and Young People's Health (ARCHY), Aston University, Birmingham B4 7ET, UK.
authors.forename: Jasdip
authors.initials: J
authors.lastname: Koner
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Rue
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK; Aston Research Centre for Children and Young People's Health (ARCHY), Aston University, Birmingham B4 7ET, UK.
authors.forename: Dan
authors.initials: D
authors.lastname: Kirby
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK; Aston Research Centre for Children and Young People's Health (ARCHY), Aston University, Birmingham B4 7ET, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Perrie
authors.affiliation: Colorcon, Inc., Harleysville, PA 19438, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Rajabi-Siahboomi
authors.affiliation: Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK; Aston Research Centre for Children and Young People's Health (ARCHY), Aston University, Birmingham B4 7ET, UK. Electronic address: a.u.r.mohammed@aston.ac.uk.
authors.forename: Afzal R
authors.initials: AR
authors.lastname: Mohammed
mesh_terms: D001639:Bicarbonates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry*; D008956:Models, Chemical; D010316:Particle Size; D016062:Porosity; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D001639:Bicarbonates; D005079:Excipients; D013607:Tablets; D008353:Mannitol; C027043:ammonium bicarbonate
keywords: Hardness; Mannitol; Orally disintegrating tablet; Particle engineering; Plasticity; Porosity; Spray drying