No abstract

Due to the poor solvent properties of hydrofluoroalkanes, suspension is often the only formulation option for respiratory drug delivery. Research in this area has focussed mainly on two main themes over the past 5 years: new design of stabilisers and particle engineering. Among the most important advances, the introduction of secondary particulate systems and the establishment of porous particles as a viable delivery system must be mentioned. Other noteworthy developments include new classes of stabilisers and surface tailoring approaches. Work has been underpinned by new theoretical insights, via the introduction of atomic force microscopy to measure particle interactions, and the development of the surface tension component approach to predict them. Future areas of development include the formulation of nanoparticles and of non-inhalation therapies in non-pressurised hydrofluoroalkanes. All these aspects are reviewed in this article.

Properties of new nonionic surfactants are reported. The amphiphiles possess two n-alkyl chains and two glucamide head-groups and have the formula (C n H2n+1)2C[CH2NHCO(CHOH)4CH2OH]2 with n = 5−9 (abbreviated here as di-(Cn-Glu)). For di-(C7-Glu) in the concentration range 0.4−8%, an upper critical solution temperature (UCST) is observed; this is unusual behavior for a nonionic surfactant. Nonetheless these materials behave like classic surfactants with regard to changes in liquid crystal phases, surface tensions, and critical micelle concentrations (cmc's) as a function of chain length n. Small-angle neutron scattering (SANS) data indicate the presence of anisotropic micelles, cylindrical for di-(C5-, 6-, and 7-Glu) but discoidal for di-(C8-Glu). There is apparently little effect of temperature (25−70 °C) on cmc or micelle structures.

It is suggested that the polar contributions of the surface free energy measurements of particles may play a crucial role in particle interaction within propellant-based systems. Together with the application of a SCA model, this approach may be capable of predicting suspension stability of pMDI formulations.