Subramanian_et_al_2016.docx (970.03 kB)
A simple approach to predict the stability of phospholipid vesicles to nebulization without performing aerosolization studies
journal contribution
posted on 2023-08-30, 14:18 authored by Sneha Subramanian, Iftikhar Khan, Oshadie Korale, Mohamed A. Alhnan, Waqar Ahmed, Mohammad Najlah, Kevin M. G. Taylor, Abdelbary M. A. ElhissiMembrane extrusion was investigated for predicting the stability of soya phosphatidylcholine liposomes and surfactosomes (Tween 80-enriched liposomes) to nebulization. Formulations were prepared with or without cholesterol, and salbutamol sulfate (SBS) or beclometasone dipropionate (BDP) were incorporated as model hydrophilic or hydrophobic drugs respectively. Formulations were extruded through 5, 2, 1 and 0.4μm polycarbonate membrane filters to study the influence of membrane pore size on drug retention by the vesicles. Surfactosomes were found to be very leaky to SBS, such that even without extrusion greater than 50% of the originally entrapped drug was lost; these losses were minimized by the inclusion of cholesterol. The smaller the membrane pore size, the greater the leakage of SBS; hence only around 10% were retained in cholesterol-free surfactosomes extruded through 0.4μm filters. To study the influence of vesicle size on SBS retained entrapment, an excessive extrusion protocol was proposed (51 extrusion cycles through 1μm filters) to compare the stability of freshly prepared vesicles (i.e. unextruded; median size approx. 4.5-6.5μm) with those previously extruded through 1μm pores. Cholesterol was essential for minimizing losses from liposomes, whilst for surfactosomes size reduction prior to extrusion was the only way to minimize SBS losses which reached up to 93.40% of the originally entrapped drug when no cholesterol was included. When extrusion was applied to BDP-loaded vesicles, greater proportions of the drug were retained in the vesicles compared to SBS. Even with extrusion through 0.4μm, BDP retention was around 50-60% with little effect of formulation. Excessive extrusion showed BDP retention using small liposomes (1μm) to be as high as 71-87%, compared to 50-66% for freshly prepared vesicles. The findings, based on extrusion, were compared to studies of vesicle stability to nebulization, published by a range of investigators. It was concluded that extrusion is a valid method for predicting the stability of liposomes to nebulization.
History
Refereed
- Yes
Volume
502Issue number
1-2Page range
18-27Publication title
International Journal of PharmaceuticsISSN
1873-3476External DOI
Publisher
ElsevierFile version
- Accepted version
Language
- eng
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Legacy posted date
2016-06-29Legacy creation date
2016-06-13Legacy Faculty/School/Department
ARCHIVED Faculty of Medical Science (until September 2018)Usage metrics
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