title: Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology.
abstract: Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are currently used in the management of asthma and chronic obstructive pulmonary disease (COPD). Localized targeted delivery of these drugs into the lungs is achieved by means of two types of inhalation devices; pressurized metered-dose inhalers (pMDIs) and dry powder-inhalers (DPIs). For environmental reasons, the chlorofluorocarbon (CFC) propellants used in pMDIs are now being replaced by ozone friendly hydrofluoroalkanes (HFAs). These new generation HFA-based pMDIs, developed to provide effective lung deposition of the active moiety, have a favorable safety and tolerability profile. However, HFA-based re-formulation of LABAs and ICS for pMDIs presents particular technical difficulties, especially in terms of ensuring dose content uniformity. This review focuses on the technology and clinical efficacy of the HFA solution pMDIs using Modulite platform technology (Chiesi Farmaceutici S.p.A). Modulite technology allows the development of HFA solution formulations that can mimic the established CFC-based drug formulations on a microgram to microgram basis and provides formulations with novel particle size distributions that improve on existing delivery systems; by manipulation of aerosol clouds and particle size, the delivery of HFA-formulated drugs can be optimized to either achieve fine particle fractions and deposition patterns similar to established CFC-based drug formulations, thus facilitating the transition to new environment-friendly pMDIs in the clinical setting, or achieve finer drug particles able to penetrate deeper into the bronchi for targeted drug delivery as medical need may dictate. Long-term, multiple-dose clinical studies of Modulite formulations of beclomethasone dipropionate (BDP), budesonide and formoterol have been demonstrated to be therapeutically equivalent to their respective previously established CFC or DPI formulations. As a result, a number of Modulite pMDIs have either recently gained regulatory approval in several European countries, or have completed clinical trials and are in the regulatory submission phase. Availability, in pMDI form, of drugs like formoterol, ICSs, and ICS/LABA combinations, all central to the effective management of asthma and COPD, is therefore expected to impact positively in assuring the continued availability of vital treatment options to patients and physicians.
authors.affiliation: Chiesi Farmaceutici S.p.A, Drug Metabolism and Pharmacokinetics, Via Palermo 26/A, 43100 Parma, Parma, Italy. d.acerbi@chiesigroup.com
authors.forename: D
authors.initials: D
authors.lastname: Acerbi
authors.forename: G
authors.initials: G
authors.lastname: Brambilla
authors.forename: I
authors.initials: I
authors.lastname: Kottakis
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D006801:Humans; D015201:Meta-Analysis as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012138:Respiratory Therapy / Q000295:instrumentation / Q000379:methods
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists