AAPS PharmSciTech

, Volume 19, Issue 5, pp 2434–2448 | Cite as

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

  • Huner K. Omer
  • Nozad R. Hussein
  • Amina Ferraz
  • Mohammad Najlah
  • Waqar Ahmed
  • Kevin M. G. Taylor
  • Abdelbary M. A. ElhissiEmail author
Research Article


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.


aerosol morphology particle size powder pulmonary 



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).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2018_1058_MOESM1_ESM.pdf (197 kb)
ESM 1 (PDF 196 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Huner K. Omer
    • 1
    • 2
  • Nozad R. Hussein
    • 1
    • 2
  • Amina Ferraz
    • 1
  • Mohammad Najlah
    • 3
  • Waqar Ahmed
    • 4
  • Kevin M. G. Taylor
    • 5
  • Abdelbary M. A. Elhissi
    • 6
    • 7
    Email author
  1. 1.Institute of Nanotechnology and Bioengineering, School of Pharmacy and Biomedical SciencesUniversity of Central LancashirePrestonUK
  2. 2.College of PharmacyHawler Medical UniversityErbilIraq
  3. 3.Faculty of Medical ScienceAnglia Ruskin UniversityChelmsfordUK
  4. 4.Nanoscience Research Group, School of Mathematics and Physics, College of ScienceUniversity of LincolnLincolnUK
  5. 5.School of PharmacyUCLLondonUK
  6. 6.Research Planning and Development, Office of Vice President for Research and Graduate StudiesQatar UniversityDohaQatar
  7. 7.College of PharmacyQatar UniversityDohaQatar

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