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

Article English OPEN
Al-Khattawi, Ali ; Koner, Jasdip ; Rue, Peter ; Kirby, Dan ; Perrie, Yvonne ; Rajabi-Siahboomi, Ali ; Mohammed, Afzal R. (2015)

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.
  • References (7)

    [1] [2] [3] [4] [5] [6] C. Telang, R. Suryanarayanan, and L. Yu, Crystallization of D-mannitol in binary mixtures with NaCl: phase diagram and polymorphism., Pharm. Res. 20 (2003) 1939-1945.

    A. Al-khattawi and A. R. Mohammed, Compressed orally disintegrating tablets: excipients evolution and formulation strategies., Expert Opin. Drug Deliv. 10 (2013) 651-663.

    H. L. Ohrem, E. Schornick, A. Kalivoda, and R. Ognibene, Why is mannitol becoming more and more popular as a pharmaceutical excipient in solid dosage forms?, Pharm. Dev. Technol. 19 (2014) 257-262.

    N. C. Alderborn G, Pharmaceutical powder compaction technology, 1st ed. New York: Marcel Dekker, 1996.

    T. Yoshinari, R. T. Forbes, P. York, and Y. Kawashima, The improved compaction properties of mannitol after a moisture-induced polymorphic transition., Int. J. Pharm. 258 (2003) 121-131.

    Y. Fu, S. Yang, S. H. Jeong, S. Kimura, and K. Park, Orally Fast Disintegrating Tablets: Developments, Technologies, Taste-Masking and Clinical Studies, Crit. Rev. Ther. Drug Carrier Syst. 21 (2004) 433-476.

    [13] [14] [15] [16] [17] [18] [19] [20] USP Convention, Disintegration <701>. Maryland: United States Pharmacopeia, 2005.

  • Metrics
    0
    views in OpenAIRE
    0
    views in local repository
    3
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Aston Publications Explorer - IRUS-UK 0 3
Share - Bookmark