The scientific basis and challenges of combination inhaled products

The recommended therapeutic regimen in the stepped management of moderate chronic obstructive pulmonary disease (COPD) and moderate asthma now involves the use of an inhaled long acting β2-agonist with a corticosteroid. A number of products have been developed that involve the incorporation of both of these drugs into a single inhaler, either as a pressurised metered dose inhaler (pMDI) or dry powder inhaler (DPI). This has been reported to lead to an improved management of the disease in comparison to administering the single active ingredients via separate inhalers. This is partly due to the improved patient compliance from using a single inhaler but in addition both physicochemical and pharmacological synergisms have been claimed when certain drug combinations (such as fluticasone propionate and salmeterol xinafoate) have been employed. However despite such combination DPIs having these advantages, the development of combination formulations is not easy since factors such as excipient (usually lactose) and individual drug characteristics (e.g. particle size distribution, fines content, crystalline character, ratio etc.) have to be considered. This is in addition to the inhaler design and the patient’s inspiration profile through the device. All these factors can affect the airways’ deposition of the two actives and possible clinical response, imposing difficulties to the ready development of new and generic products.