Aerosolization and hygroscopic growth evaluation of lyophilized liposome aerosols under controlled temperature and relative humidity conditions

Abstract

An experimental apparatus was developed that aerosolized lyophilized liposome powders over extended periods under well-controlled and selectable conditions of temperature and relative humidity (RH). Four types of Multilamellar Large Vesicle liposomes (dilauroyl-phosphatidylcholine [DLPC], dimyristoyl-phosphati-dylcholine [DMPC], dipalmitoyl-phosphatidylcholine [DPPC], and distearoyl-phos-phatidylcholine [DSPC]) were lyophilized (freeze dried) for study in the system as a first step in their evaluation as drug carrier candidates for inhalation therapy applications. Conditions of 25°C temperature and 13–100% RH were used. Aerosol Mass Median Aerodynamic Diameters (MMADs) were measured using a time-of-flight aerodynamic particle sizer. The formulations exhibited different handling and hygroscopic growth characteristics. DLPC and DMPC were difficult to manipulate and aerosolize under all conditions; in contrast, DPPC and DSPC were easily manipulated and readily aerosolized. MMADs at the lowest RH used (13%-15%) ranged from 1.31 μm (DPPC) to 1.54 μm (DLPC). All formulations exhibited hygroscopic growth of RH 75% or higher. Growth ratios, i.e. the ratio of MMAD at a given RH to MMAD at the lowest RH used, were maximum at 95–100% RH and were: DMPC 1.67, DLPC 1.27, DSPC 1.23, and DPPC 1.15. Maximum MMADs occurred at 95%-100% RH and ranged from 1.51 /am (DPPC) to 2.2 /am (DMPC), still well within the respirable range. Hygroscopic growth was not clearly demonstrated below 55% RH. These results demonstrated that (1) the experimental apparatus was an effective tool for aerodynamic study of lyophilized liposome powders, (2) lyophilized liposomes may have practical application as dry powder pharmaceutical aerosols,(3) hygroscopic growth may have little influence on aerosol particle size and respiratory tract deposition, regardless of formulation, and (4) DSPC and DPPC appear more attractive than DMPC and DLPC for future study. © 1996 Taylor & Francis Group, LLC.