Aerosol characterization of nebulised liposomes co-loaded with erlotinib and genistein
Nattika Nimmano1, Satynarayana Somavarapu1 & Kevin M.G Taylor1
1Department of Pharmaceutics, UCL School of Pharmacy, London, 29-39 Brunswick Square, WC1N 1AX, United Kingdom
Erlotinib and genistein co-loaded liposomes comprising DPPC (1,2- dipalmitoyl- sn- glycerol- 3- phosphocholine), cholesterol and DOPE (1,2-dioleyl- sn- glycerol- 3- phosphoethanolemine) (mole ratio 72:8:20) were prepared by thin-film hydration followed by probe-sonication to achieve vesicles with a mean diameter of 100 to 200 nm. The entrapment efficiency of genistein was 10 times higher than for erlotinib, being approximately 100% and 10%, respectively. Thermal analysis using High Sensitivity Differential Scanning Calorimetry (HSDSC) showed that drug incorporation into DPPC liposomes resulted in an increase in the fluidity of the phospholipid bilayer, indicating incorporation into the bilayer regions. The properties of aerosols generated from liposomal dispersions using air-jet and vibrating-mesh nebulisers were investigated and evaluated using the Next Generation Impactor (NGI) and Fast Screening Impactor (FSI) after cooling the impactors at 5°C for at least 90 min. The FSI was found to be simple to use and labour-saving for simple aerosol characterization, with similar performance compared to the NGI. The vibrating-mesh nebuliser generated a significantly higher emitted dose than the air-jet nebulisers (p<0.05), being approximately 50% and 30%, respectively. However, the air-jet device gave a two-fold higher (40% compared to 20%) Fine Particle Fraction (FPF) measured using the FSI at a flow rate of 15 L/min for 10 min. Air-jet and vibrating-mesh nebulisers produced no significant difference for the Fine Particle Dose (FPD) of erlotinib (p>0.05). However, the air-jet nebuliser generated significantly higher FPD for the aerosol of genistein (p<0.05).