Budesonide Modulite ®: Improving the changeover to CFC-free treatments

Abstract

Inhaled corticosteroids have been recommended by national and international guidelines as the mainstay for anti-inflammatory treatment in patients with bronchial asthma. Inhaled corticosteroids are delivered by a variety of devices such as pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs) and nebulizers. The choice of the devices is dependent on a number of clinical factors such as severity of the disease, ability of the patient to proper usage of the device and the preference of the patient and the doctor. The latter is not always based on strong arguments. Inhalation therapy for treatment of bronchial asthma is performed since more than 200 years using ‘‘asthma cigarettes’’. The first Jet-Nebulizers were brought up in the 1930s, and in 1956, the first CFC-containing pMDI was marketed (Riker Medihaler). These devices were mainly used to deliver inhaled beta-agonists and anticholinergics to the patient, with the benefit of rapid onset of action as compared to the traditional oral route. It took nearly 20 years to develop an inhaled corticosteroid with limited side effects due to a significant first pass metabolism. Dry powder inhalers were developed later. The majority of asthmatic patients is using pMDIs worldwide. The popularity of these devices is based on their design as they are easy to use, small and portable. pMDIs designed by different companies look much more alike than DPIs. The effect of a certain drug delivered by the respiratory route is dependent on a variety of different factors which amongst others are the ability of the patient to inhale correctly and to produce a sufficient inspiratory flow. Drug deposition and the local and systemic metabolism of the compound are important factors determining the effect and the side-effects. Recently, the technology to design and produce devices for respiratory delivery has improved markedly. However in contrast to the progress in inhaler technology, adherence and compliance to the recommended therapy with inhaled corticosteroids remain a serious problem which has to be minimized in order to ensure the clinical benefit of inhaled corticosteroids in patients with bronchial asthma. Chlorofluorocarbons (CFCs) have been used in many products such as refrigeration, plastics, nonmedical aerosol, etc. pMDIs traditionally have been formulated using CFC propellants 11 and 12. The emission of CFCs into the atmosphere is harmful to the ozone layer. This resulted in an Environmental Program under the auspices of the United Nations, and over 40 nations agreed to the Montreal protocol in 1987 for the reduction and later for the cessation of the use of CFCs. The production of CFCs was stopped in 1996 except for ‘‘essential uses’’. Essential uses included the manufacturing of pMDIs containing drugs for patients with airway diseases (asthma and COPD) and on therapy with pMDIs. The European Commission (Strategy for the Phase-Out of CFCs in Metered Dose Inhalers) decided later the criteria according to which CFC containing inhalers should be withdrawn. After years of research in this area, hydrofluoroalkane (HFA) 134a (norflurane) was selected as a ARTICLE IN PRESS