title: Elaborating the phase behaviour of ethylene oxide oligomers and analogues in 2H, 3H-perfluoropentane.
abstract: Pressure metered dose inhalers (pMDIs) are seen as an attractive option for the delivery of active molecules to the bloodstream via the lungs. Formulation issues are important as it is necessary to disperse the active substance into a volatile propellant. The phase behaviour of a range of common formulation agents - excipients - in 2H, 3H-perfluoropentane is reported here, focussing on the effects of simple elaboration of a central ethylene-oxide (EO) moiety. The base series of hydroxyl terminated EO fragments exhibited lower consolute solution temperature (LCST) behaviour that was strongly molecular weight-dependent. Substitution of methyl groups in place of the hydroxyl groups at the terminus of the EO fragment had a pronounced effect on the solubility of the oligomeric or polymeric material, the material becoming fully miscible with the HPFP. Substitution of methyl groups along the backbone of the hydroxyl terminated EO greatly enhanced the solubility of the materials, but the exhibited phase behaviour was still that of LCST. Longer alkyl groups at the terminus of the EO were found to promote the solubility compared to the hydroxyl terminated material, but to a relatively smaller degree compared with the methyl group. It is hoped that these simple "design rules" should facilitate the development of designer excipients tailored for a particular application.
authors.affiliation: School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3TB, United Kingdom. griffithspc@cardiff.ac.uk
authors.forename: Peter C
authors.initials: PC
authors.lastname: Griffiths
authors.forename: Marie
authors.initials: M
authors.lastname: Côte
authors.forename: Philippe G A
authors.initials: PG
authors.lastname: Rogueda
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D036501:Metered Dose Inhalers; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D010420:Pentanes
chemical_list: D004337:Drug Carriers; D005079:Excipients; D005466:Fluorocarbons; D011092:Polyethylene Glycols; D013501:Surface-Active Agents; C008806:perfluoropentane; D010420:Pentanes