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Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler

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Abstract

Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated ‘worm-like’ structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent.

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Acknowledgements

We thank MIAT, Italy for supplying us with the Monodose dry powder inhaler device. We also thank Mr. David McCarthy, Microscopy unit, UCL-School of Pharmacy for the TEM images and Lipoid, Switzerland for supplying us with SPC (Lipoid S-100).

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Authors and Affiliations

  1. Institute of Nanotechnology and Bioengineering, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK

    Huner K. Omer, Nozad R. Hussein & Amina Ferraz

  2. College of Pharmacy, Hawler Medical University, Erbil, Iraq

    Huner K. Omer & Nozad R. Hussein

  3. Faculty of Medical Science, Anglia Ruskin University, Chelmsford, CM1 1SQ, UK

    Mohammad Najlah

  4. Nanoscience Research Group, School of Mathematics and Physics, College of Science, University of Lincoln, Lincoln, LN6 7TS, UK

    Waqar Ahmed

  5. School of Pharmacy, UCL, 29-39 Brunswick Square, London, WC1N 1AX, UK

    Kevin M. G. Taylor

  6. Research Planning and Development, Office of Vice President for Research and Graduate Studies, Qatar University, P.O. Box 2713, Doha, Qatar

    Abdelbary M. A. Elhissi

  7. College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar

    Abdelbary M. A. Elhissi

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  1. Huner K. Omer
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Omer, H.K., Hussein, N.R., Ferraz, A. et al. Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler. AAPS PharmSciTech 19, 2434–2448 (2018). https://doi.org/10.1208/s12249-018-1058-4

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