title: A simple approach to predict the stability of phospholipid vesicles to nebulization without performing aerosolization studies.
abstract: Membrane 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 0.4 μm 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 0.4 μm filters. To study the influence of vesicle size on SBS retained entrapment, an excessive extrusion protocol was proposed (51 extrusion cycles through 1 μm filters) to compare the stability of freshly prepared vesicles (i.e. unextruded; median size approx. 4.5-6.5 μm) with those previously extruded through 1 μm 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 0.4 μm, BDP retention was around 50-60% with little effect of formulation. Excessive extrusion showed BDP retention using small liposomes (1 μm) 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.
authors: Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
authors: Sneha
authors: S
authors: Subramanian
authors: Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
authors: Iftikhar
authors: I
authors: Khan
authors: Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
authors: Oshadie
authors: O
authors: Korale
authors: Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
authors: Mohamed Albed
authors: MA
authors: Alhnan
authors: Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Medicine, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
authors: Waqar
authors: W
authors: Ahmed
authors: Faculty of Medical Science, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, United Kingdom.
authors: Mohammad
authors: M
authors: Najlah
authors: Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors: Kevin M G
authors: KM
authors: Taylor
authors: Pharmaceutical Sciences Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: aelhissi@qu.edu.qa.
authors: Abdelbary
authors: A
authors: Elhissi
mesh_terms: D000336:Aerosols; D000420:Albuterol / Q000737:chemistry; D001507:Beclomethasone / Q000737:chemistry; D001993:Bronchodilator Agents / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004355:Drug Stability; D008081:Liposomes / Q000737:chemistry*; D008567:Membranes, Artificial; D009330:Nebulizers and Vaporizers; D010743:Phospholipids / Q000737:chemistry*; D011076:Polycarboxylate Cement; D011136:Polysorbates / Q000737:chemistry; D013678:Technology, Pharmaceutical
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D008081:Liposomes; D008567:Membranes, Artificial; D010743:Phospholipids; D011076:Polycarboxylate Cement; D011136:Polysorbates; C005506:polycarbonate; D002784:Cholesterol; D001507:Beclomethasone; D000420:Albuterol
keywords: Aerosol; Drug delivery; Drug development; Extruder; Nebulizer