Modulite: a simple solution to a difficult problem.

The development of HFA-based pMDIs has proved difficult due to differences in the physico-chemical properties of CFC and HFA propellants. However, the development of solution formulations instead of suspensions has provided a way to formulate products whose cloud characteristics can be modulated in a controlled manner by permitting different formulation and device hardware variables. The new approach has proved successful in formulating several different drugs including steroids and has now been applied to developing a formoterol Modulite solution formulation characterized by good chemical stability, delivery performance, and clinical results.

Fenoterol hydrobromide delivered via HFA-MDI or CFC-MDI in patients with asthma: a safety and efficacy comparison.

The main objective of the study was to compare the long-term safety and tolerability of fenoterol hydrobromide delivered using a metered-dose inhaler formulated with the alternative propellant, hydrofluoroalkane 134a (HFA-MDI), with delivery using the currently available chlorofluorocarbon MDI (CFC-MDI; Berotec 100). A further objective was to compare the efficacy of fenoterol HFA-MDI with fenoterol CFC-MDI, using the pulmonary function parameters of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). Following a 2-week run-in phase, a 12-week, double-blind parallel group comparison was undertaken in 290 patients randomized on a 2:1 basis to two puffs of 100 microg fenoterol four times a day (HFA-MDI=197 patients; CFC-MDI=93 patients). A total of 236 patients in this multi-centre study completed the trial as planned. The overall incidence of adverse events (AEs) was similar in both groups (29.9% of HFA-MDI patients and 28% of CFC-MDI patients). Reports of respiratory disorder AEs were also comparable (21.8% HFA-MDI; 22.6% CFCMDI). End of study laboratory tests, ECG, pulse, blood pressure and physical examination showed no significant differences from pre-study baselines in either group and both treatments appeared to be well tolerated. Pre-dose FEV1 measurements taken at the three clinic visits were constant and increase in FEV1 at 5 and 30 min post-dose demonstrated equivalent efficacy for the two formulations. No difference between the two groups was observed in PEF or in the use of rescue medication. We conclude from these findings that the long-term safety and efficacy profile of fenoterol HFA-MDI is comparable to that of the fenoterol CFC-MDI.

Issues surrounding MDI formulation development with non-CFC propellants.

Reformulation of metered-dose inhalers (MDIs) without the use of chlorofluorocarbon (CFC) propellants presents numerous obstacles because there are no alternative propellants that can serve as immediate replacements for pharmaceutical use. Hydrofluorocarbons (HFCs), hydrochlorofluorocarbons (HCFCs) and hydrocarbons (HCs) are all under consideration as possible alternatives for CFC propellants. However, no single propellant or combination of propellants has been identified with all of the physical-chemical properties of CFCs. Based on their zero ozone depletion potentials, relatively low global warming potentials, non-flammabilities, densities, and vapor pressures, HFA-134a and HFA-227 are the most attractive replacement propellants identified to date. Yet, their use in MDIs will still require: (1) identification of a metering valve with propellant and formulation-compatible gaskets, (2) use of current suspending agents at levels much lower than in present MDIs or identification (and characterization) of new suspending agents, and (3) modification of existing manufacturing technologies. Demonstration of acceptable final product stability, safety and efficacy will be necessary prior to submission to worldwide registration authorities.

[Atomizers for disinfection]. / Raspyliaiushchaia apparatura dlia dezinfektsii.

The disinfection services experience acute demand for atomizers. In view of the fact that operation of all atomizing units is based on the same physical principles and that their use is associated with the solution of the same physical problems, for disinfection needs, use can be made of the equipment manufactured by medical industry as well as of the analogous units applied in related spheres: in veterinary, field-crop cultivation, forestry, horticulture, in carrying out finishing works during construction, and in homes. Atomizers manufactured by different bodies are reviewed. The main characteristics of the units are provided.

[Hygienic characteristics of machines for the surface chemical protection of plants]. / Gigienicheskaia kharakteristics mashin dlia nazemnoi khimicheskoi zashchity rastenii.

Pesticide spraying machines for agricultural crops were hygienically assessed, the analysis covered the machines of three generations. The prospects of quick introduction of scientific hygienic achievements into the production of machines intended for chemization of agriculture lie in creative cooperation between engineers and hygienists.

Assessment of jet nebulisers for lung aerosol therapy.

The effect on nebuliser output of varying the flow rate of compressed air driving the device and the volume of respirator solution used was investigated in four brands of jet nebuliser. Raising the airflow rate from 4 to 6 1/min reduced the duration of nebulisation by approximately 40%, and a rise from 6 to 8 1/min reduced the duration by a further 15%. However, this change had only a slight effect on the proportion of the solution released. The volume of respirator solution placed in the nebuliser directly influenced the volume released as aerosol. After a 2 ml fill, less than 1 ml was released (50%). With a volume fill of 4 mg 60-80% was released, and with 6 ml 70-85% was released. Nebuliser output fell during nebulisation as the temperature of the solution dropped by 8-12 degrees C. A minimum 4 ml fill and an air-flow rate of 6 l/min are advocated to optimise nebuliser output.