A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

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 degrees C. Compacts were prepared at 151 MPa 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 +/- 5.29 s for pure mannitol to 75.33 +/- 2.52-31.67 +/- 1.53 s for mannitol 110-170 degrees C. Hardness increased by 150% at 110 degrees C (258.67 +/- 28.89 N) and 30% at 150 degrees C (152.70 +/- 10.58 N) compared to pure mannitol tablets (104.17 +/- 1.70 N). 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 alpha and beta polymorphs formed upon spray drying. (C) 2015 Elsevier B.V. All rights reserved.