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Freeze-Dried Mannitol for Superior Pulmonary Drug Delivery via Dry Powder Inhaler

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Abstract

Purpose

To show for the first time the superior dry powder inhaler (DPI) performance of freeze dried mannitol in comparison to spray dried mannitol and commercial mannitol.

Methods

Different mannitol powders were sieved to collect 63–90 μm particles and then analyzed in terms of size, shape, surface morphology, solid state, density, flowability. Salbutamol sulphate-mannitol aerosol formulations were evaluated in terms of homogeneity, SS-mannitol adhesion, and in vitro aerosolization performance.

Results

Freeze dried mannitol demonstrated superior DPI performance with a fine particle fraction believed to be highest so far reported in literature for salbutamol sulphate under similar protocols (FPF = 46.9%). To lesser extent, spray dried mannitol produced better aerosolization performance than commercial mannitol. Freeze dried mannitol demonstrated elongated morphology, α-+β-+δ- polymorphic forms, and poor flowability whereas spray dried mannitol demonstrated spherical morphology, α-+β- polymorphic forms, and excellent flowability. Commercial mannitol demonstrated angular morphology, β- polymorphic form, and good flowability. Freeze dried mannitol demonstrated smoother surface than spray dried mannitol which in turn demonstrated smoother surface than commercial mannitol. FPF of SS increased as mannitol powder porosity increase.

Conclusions

Freeze drying under controlled conditions can be used as a potential technique to generate aerodynamically light mannitol particles for superior DPI performance.

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Acknowledgments and Disclosures

Waseem Kaialy thanks Dr. Ian Slipper (University of Greenwich) and Mr. Ian Brown (University of Kent) for help provided with SEM and AFM analysis respectively.

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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, Syria

    Waseem Kaialy

  3. Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Nokhodchi

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  1. Waseem Kaialy
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  2. Ali Nokhodchi
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Correspondence to Waseem Kaialy.

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Kaialy, W., Nokhodchi, A. Freeze-Dried Mannitol for Superior Pulmonary Drug Delivery via Dry Powder Inhaler. Pharm Res 30, 458–477 (2013). https://doi.org/10.1007/s11095-012-0892-4

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  • DOI: https://doi.org/10.1007/s11095-012-0892-4

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