Spray-Dried Proliposome Microparticles for High-Performance Aerosol Delivery Using a Monodose Powder Inhaler
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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.
KEY WORDSaerosol 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.
- 9.Cipolla D, Blanchard J, Gonda I. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics. 2016;8 https://doi.org/10.3390/pharmaceutics8010006.
- 13.Elhissi AMA, Karnam KK, Danesh-Azari M-R, Gill HS, Taylor KMG. Formulations generated from ethanol-based proliposomes for delivery via medical nebulizers. J Pharm Pharmacol 2006. 2006;58:887–94.Google Scholar
- 17.Radhakrishnan, R., Mihalko, P.J., Abra, R.M. Method and apparatus for administering dehydrated liposomes by inhalation. US patent No 4895719, 1990.Google Scholar
- 30.Cevher E, Orhan Z, Mülazimoğlu L, Sensoy D, Alper M, Yildiz A, et al. Characterization of biodegradable chitosan microspheres containing vancomycin and treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with prepared microspheres. Int J Pharm. 2006;317:127–35.CrossRefPubMedGoogle Scholar
- 36.Abbas KA, Lasekan O, Khalil SK. The significance of glass transition temperature in processing of selected fried food products: a review. Modern Appl Sci. 2010;4:3–21.Google Scholar
- 37.Truong V. Glass transition temperature and spray drying of sugar-rich foods: modelling and stickiness. LAP LAMBERT Academic Publishing, Saarbrücken, 2014.Google Scholar
- 41.Yu, L., Mishra, D.S., Rigsbee, D.R., 1998. Determination of the glass properties of D-mannitol using sorbitol as an impurity. J Pharm Sci, 87:774–777.Google Scholar
- 47.Dozan T, Benkovic´ M, Bauman I. Sucrose particle size reduction—determination of critical particle diameters causing flowability difficulties. J Hyg Eng Des. 2014;8:3–10.Google Scholar
- 48.Wang, J., Shi, Q., Huang, Z., Gu, Y., Musango, L., Yang, Y., 2015. Experimental investigation of particle size effect on agglomeration behaviors in gas–solid fluidized beds. Ind Eng Chem Res, 54:12177–12186.Google Scholar
- 61.Bennett RC, Brough C, Miller DA, O’Donnell KP, Keen JM, Hughey JR, et al. Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol dispersing: approaches to enhance solubility of a poorly water-soluble gum extract. Drug Dev Ind Pharm. 2015;41:382–97.CrossRefPubMedGoogle Scholar
- 79.Carr R. Evaluating flow properties of solids. Chem Eng. 1965;72:163–8.Google Scholar
- 85.Abadelah M, Chrystyn H, Bagherisadeghi G, Abdalla G, Larhrib H. Study of the emitted dose after two separate inhalations at different inhalation flow rates and volumes and an assessment of aerodynamic characteristics of indacaterol Onbrez Breezhaler® 150 and 300 μg. AAPS PharmSciTech. 2018;19:251–61.CrossRefPubMedGoogle Scholar