Does glycerol interact with dipalmitoylphosphatidylcholine membranes?

Wachirun Terakosolphan, Precious Akhuemokhan, Richard Harvey, Ben Forbes

In some solution-based pressurised metered dose inhalers (pMDIs), glycerol is used as a non-volatile excipient in order to adjust the aerosol droplet size into the micron range. After actuation, the volatile components of the pMDI formulation evaporate, leaving the drug and glycerol to form the respirable particles. Although the purpose of glycerol is to modify the aerosol particle size distribution, evidence is emerging that it may affect drug kinetics after the particles deposit on the surface of the respiratory tract. Liposomes or monolayers formed from dipalmitoylphosphatidylcholine (DPPC) can be employed as simple models of the epithelial cell membrane, and are used in many pharmaceutical studies to examine the drug absorption or membrane interaction. DPPC also predominates the composition of lung surfactant which coats the mucosa at the glycerol-containing drug particles deposition site. The purpose of this investigation was to conduct a preliminary screen to determine whether glycerol interacts with biomimetic DPPC models as a precursor to more detailed studies into mechanisms that may explain differences in drug permeability in human airways. A fluorimetric assay using laurdan as a fluorescent probe was designed to measure glycerol-DPPC interactions which alter the lipid phase transition temperature. Increasing the concentration of glycerol solution (0, 1.0, 5.0, 10.0, 20.0, and 30.0% w/w) in the DPPC liposome system produced incremental increases in phase transition temperature from 42.6 to 44.2°C. Thus, it can be inferred that glycerol has the potential to modify the molecular rigidity of membrane components which may influence drug permeability in the respiratory tract.

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