By Jason A Suggett, Mark W Nagel, Dominic P Coppolo, and Jolyon P Mitchell
A wide spectrum of options is available for delivering inhaled medications by nebulization. The challenge, either for a developer considering which delivery option to use for their new formulation, or for a clinician prescribing therapy that will be funded either privately or through an insurance payer/government medical program, is to find the sweet-spot where the required features and performance is provided at the lowest cost.
Despite the proliferation of other classes of orally inhaled product (OIP), nebulizer systems are still widely used to deliver inhaled aerosol therapies as aqueous droplets because they do not necessarily require the patient to undertake a specific inhalation maneuver; instead, except for certain breath-controlled systems, the patient just needs to breath tidally, as normal when relaxed. This situation is in contrast with medication delivery either by pressurized metered dose inhaler (pMDI) where the patient has to coordinate actuation with a slow inhalation followed by a breath-hold or by passive dry powder inhaler (DPI) where the user is instructed to inhale forcefully and deeply in order to disperse the powder efficiently.
Furthermore, formulation development for delivery by nebulizer is a relatively simple process compared with the procedures needed for delivery by either pMDI or DPI. High mass delivery of one or more active pharmaceutical ingredients (APIs) is also possible via nebulizer. For example, a 5 mL ampule of TOBI tobramycin solution for inhalation is formulated with 300 mg of drug product. Many APIs are only available for inhaled delivery via the nebulizer route of administration for these reasons, as well as the need to achieve compatibility of the formulation with the delivery platform as with Cayston aztreonam, an antibiotic delivered by a vibrating membrane nebulizer as an inhalation solution for support therapy in cystic fibrosis.
A number of sophisticated nebulizer systems have been developed as the result of increased concern regarding poor patient compliance with all types of orally inhaled product, as well as the desire for better targeting of often expensive formulations to specific regions of the lungs.
These drivers have been focused on achieving the following goals:
- to provide feedback to the user to encourage optimum inspiratory profiles beyond the basic flow rate-elapsed time profile characteristic of relaxed tidal breathing that had hitherto been the norm when receiving nebulizer-based therapy;
- to allow one-, or better, two-way communication of data from/to the patient using the inhaler to/from the clinician to enable better support to patients, especially those with poor inhalation technique;
- to minimize wastage when the medication being delivered is expensive by reducing the dead (residual) volume of liquid retained by the nebulizer after therapy.
While these goals are laudable from the standpoint of delivering effective therapy, they can come at a considerable cost to the payer, often in the high hundreds or even thousands of dollars. Such pricing may well offer value in certain situations where a developer of a specific drug / device combination product has a “must have” requirement for the added features. The conundrum the developers are faced with, is how many features are “must haves” and what additional cost is bearable. Significant added cost to the device is likely unjustifiable for the treatment of the classic obstructive lung diseases such as asthma and COPD where the medication cost component is relatively low in comparison with the cost of new formulations that are often developed to target diseases with relatively low numbers of patients.
