ProAir(®) HFA delivers warmer, lower-impact, longer-duration plumes containing higher fine particle dose than Ventolin(®) HFA.

BACKGROUND: Inhaler technique and spray characteristics are critical for adequate management of asthma symptoms with pressurized metered-dose inhalers (pMDIs). A lower spray force has been directly associated with a decrease in throat deposition of asthma medication, and a higher spray temperature may alleviate the "cold Freon effect" associated with pMDIs. The objective of the study was to characterize and compare the temperature, maximum spray force, and duration of the emitted plume from two pMDIs: ProAir(®) hydrofluoroalkane (HFA) and Ventolin(®) HFA. METHODS: A spray force tester model SFT1000 and thermocouple were used to test 10 units from three separate lots (total of 30 units) of each inhaler type. Three consecutive actuations were tested at a spray distance of 40 mm from the edge of the mouthpiece. Room temperature, humidity, and initial weight of the pMDI were recorded. Final weight of each pMDI was recorded to determine the spray weight of individual actuations. pMDIs were primed and operated according to instructions provided in the package insert. Aerodynamic particle size distribution (APSD) was also assessed using a next-generation impactor at a flow rate of 28.3 L/min. RESULTS: Measurements were obtained from three consecutive actuations for each of 30 units of ProAir(®) HFA and Ventolin(®) HFA (10 units from three separate lots), resulting in a total of 90 actuations tested for each pMDI. Minimum plume temperatures recorded were 7.2 ± 0.7°C and -35.9 ± 12.7°C, respectively, for ProAir(®) HFA and Ventolin(®) HFA. ProAir(®) HFA produced more than a twofold greater plume duration (385 ± 46 ms vs. 156 ± 58 ms; p<0.001) and a significantly lower mean maximum spray force (33.6 ± 11.4 mN vs. 75.9 ± 12.0 mN; p<0.0001) compared with Ventolin(®) HFA. APSD analysis demonstrated that ProAir(®) HFA produced almost twice as much fine particle (<5 µm) dose with lower geometric standard deviation, compared with Ventolin(®) HFA. Two inhalers produced similar mass median aerodynamic diameters, ranging from 2.3 to 2.4 µm. CONCLUSIONS: The ProAir(®) HFA delivers a warmer, lower-impact, and longer-lasting plume compared with Ventolin(®) HFA, which may provide a more consistent, comfortable experience for patients using a pMDI. ProAir(®) HFA produces higher fine particle dose than Ventolin(®) HFA.

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium.

Enhanced immunogenicity of a hepatitis B virus peptide vaccine using oligosaccharide ester derivative microparticles.

Controlled release microspheres can overcome many of the disadvantages of multiple vaccine delivery such as rate of uptake and cost of administration. Proteins and peptides are difficult to administer using conventional polymers owing to protein degradation, premature release and stability. Here we report the successful development of room temperature stable, controlled release formulations using oligosaccharide ester derivatives (OEDs) of trehalose and a synthetic peptide analogue of hepatitis B surface antigen. Employing a range of different OED preparations, we have optimised the immunogenicity of the peptide formulation such that mice injected with a single preparation of microspheres consisting of trehalose octaacetate (TR101; Group G) produce high titre anti-hepatitis B (anti-HBs) surface antigen antibodies. The kinetics of the immune response could be manipulated with different peptide/OED formulations and correlated with the OED composition of the microspheres. Our data demonstrate the considerable potential of OED microspheres as novel delivery systems for vaccines. The ability to induce strong immune responses, without the requirement for multiple doses or cold-chain storage, could radically improve vaccination programmes in developing countries.