Elhissi, Abdelbary Mohammed Abdelbary; (2006) Proliposome formulations for delivery via medical nebulisers. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This study aims to investigate the ability of proliposomes to generate liposomes for delivery using air-jet, ultrasonic and vibrating-mesh nebulisers. Particulate-based proliposomes successfully generated liposomes under static conditions. Manually dispersed proliposomes generated multilamellar vesicles, with formulation having a small effect on the liposome size. Using sucrose as a carrier, liposomes were generated or dispersed in situ from proliposomes within the medical nebulisers investigated. The Pari (air-jet) and the Omron (vibrating-mesh) nebulisers produced large mass and lipid outputs with a large lipid fraction deposited in the lower stage of a two stage impinger. The Liberty (Ultrasonic) nebuliser failed to deliver more than 6% of the lipid employed. Multilamellar liposomes were generated from ethanol-based proliposomes. The resultant vesicles entrapped 62% of the available salbutamol sulphate compared to only 1.23% entrapped by liposomes made by the thin film method. Aeroneb Pro or Aeroneb Go vibrating-mesh nebulisers generated aerosol droplets of larger volume median diameter and narrower size distribution than the Pari (air-jet) nebuliser. Unlike the vibrating-mesh nebulisers, the performance of the jet nebuliser was largely independent of formulation. A nebuliser-dependent significant loss of the originally entrapped drug was demonstrated. A customised large mesh Aeroneb Pro reduced the drug losses during nebulisation. High sensitivity differential scanning calorimetry showed that the phospholipid phase transitions and liposomal bilayer interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no pretransition, with a very low incorporation of the steroid (max. 1 mole%). This was attributed to an alcohol-induced interdigitation of the bilayers. 1 to 2.5 mole% steroid seemed to be optimal for incorporation in liposomes manufactured by the thin film or particulate-based proliposome method. Jet-nebulisation of particulate-based proliposomes delivered vesicles with enhanced steroid incorporation compared to liposomes generated by manual dispersion of these proliposomes.

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