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The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance

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Abstract

Purpose

To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures.

Methods

Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using anti-solvent precipitation technique. Obtained crystals were sieved to separate 63–90 μm size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC.

Results

At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals’ width and thickness. Crystallised β-lactose showed different anomers compared to commercial lactose (α-lactose monohydrate). Crystallised α-mannitol showed different polymorphic form compared to commercial mannitol (β-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to α-mannitol, α-lactose monohydrate, β-lactose, 5α-/3β-lactose and 4α-/1β-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers.

Conclusion

The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.

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Acknowledgments & DISCLOSURES

Waseem Kaialy thanks Dr Ian Slipper (School of Science, University of Greenwich) for taking SEM images. The authors also thank Roquette for providing mannitol samples.

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Authors and Affiliations

  1. Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK

    Waseem Kaialy & Ali Nokhodchi

  2. Pharmaceutics and Pharmaceutical Technology Department, University of Damascus, Damascus, 30621, Syria

    Waseem Kaialy

  3. Faculty of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, West Yorkshire, HD1 3DH, UK

    Hassan Larhrib

  4. King’s College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK

    Gary P. Martin

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  1. Waseem Kaialy
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  2. Hassan Larhrib
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  4. Ali Nokhodchi
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Correspondence to Ali Nokhodchi.

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Kaialy, W., Larhrib, H., Martin, G.P. et al. The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance. Pharm Res 29, 2139–2156 (2012). https://doi.org/10.1007/s11095-012-0743-3

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  • DOI: https://doi.org/10.1007/s11095-012-0743-3

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