استنشاق دوز اندازه گیری شده فشرده برای داروهای چند دوزی در درمان بیماری های تنفسی Co-suspension delivery technology in pressurized metered-dose inhalers for multi-drug dosing in the treatment of respiratory diseases

1. Introduction Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with multiple components, including chronic inflammation, airway obstruction, and airway hyperresponsiveness [1]. Numerous medications are available for asthma and COPD, most of which are administered by oral inhalation devices [2,3]. The first propellant-based, pressurized metered-dose inhalers (pMDIs) were developed in the mid-1950s [4,5], beginning an era of portable and compact modern inhalers with highly efficient aerosolization engines. Oral inhalation is the standard method of medication administration for patients with asthma [6] and COPD [7] as it achieves targeted drug delivery to the lungs. Direct administration to the airways has several advantages over systemic administration, including rapid delivery of low doses to the airways [3] and reduced potential for adverse events, as well as increased efficacy [8]. Asthma and COPD are distinct diseases with defined treatment paradigms and objectives, but are currently treated with many of the same classes of inhaled medications due to their overlapping disease features [2,7]. Moreover, both are chronic diseases that require continued maintenance therapies, often with escalating interventions [9,10]. Treatment escalation can involve administration of multiple drugs and may require use of multiple inhaler devices. The use of different drugs from different delivery systems can be confusing for patients, and potentially increase errors in inhaler technique. Thus, the availability of different fixed-dose combinations in a single inhaler device may be beneficial, allowing escalation or de-escalation without changing the inhaler device. Potential combinations include: (1) bronchodilator combinations (e.g., long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) for patients with COPD; (2) an antiinflammatory drug plus a bronchodilator (e.g., inhaled corticosteroid [ICS]/LABA) for patients with asthma or COPD; or, although currently still in clinical development, (3) triple therapy (e.g., ICS/ LAMA/LABA) for patients with asthma or COPD.