New Developments in Aerosol Delivery Aim to Improve Therapeutic Efficacy

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Wayne Kuznar

Almost two thirds of patients and clinicians do not know the proper inhaler technique to get the maximal benefit of drug treatment for chronic obstructive pulmonary disease (COPD). A panel discussion focused on current and future aerosol drug delivery at Chest 2010.

The effectiveness of aerosolized drug delivery depends on the patient, the properties of the propellant and the drug, and the type of inhaler. Inhalers have as many as 17 steps for typical use and some types require synchronization between inspiration of breath and aerosol actuation or a constant breathing pattern, said James Fink, PhD, Adjunct Professor, Georgia State University, Atlanta, and an independent consultant to the biotechnology industry.

Even with perfect inhalation technique, however, deposition of particles can be limited by airway geometry, which is altered by the presence of COPD and other airway diseases.

Inhalers can be classified as pressurized metered-dose inhalers (MDIs), dry powder inhalers, or jet or ultrasonic nebulizers.

The major drawback of conventional pressurized MDIs and dry powder inhalers is inefficient delivery of drug to the lungs; only about 10% to 40% of the drug reaches the lungs.

Myrna B. Dolovich, PEngSeveral design changes have been made to inhalers to promote more efficient drug delivery, including production of particles within the extra-fine range to target the deep lung, said Myrna B. Dolovich, PEng, Associate Clinical Professor, Division of Respirology, McMaster University, Canada.

Pressurized Metered-Dose Inhalers
Spacers are now used with many pressurized MDIs to collect large particles that would normally be deposited in the mouth or the back of the throat. Although spacers have little effect on the concentration of drug deposited in the lungs, they reduce the total amount of the drug deposited in the body. (Lung penetration is determined by the size of drug particles in the aerosol; only particles between 1 μm and 5 μm in diameter reach the airway.)

Newer pressurized MDIs have breath-synchronized devices to control inhalation. Actuators have recently been introduced that will improve the efficacy and efficiency of pressurized MDIs by increasing the respirable fraction of drug delivered, which will also serve to reduce side effects.

Ozone-damaging chlorofluorocarbons (CFCs) must be phased out of medical devices per the Montreal Protocol obligations, and are being replaced by hydrofluoroalkaline propellants. The Modulite is a CFC-free MDI with beclomethasone dipropionate as its constituent. Particle size is smaller to achieve greater lung penetration and the aerosol is slower moving compared with CFC pressurized MDIs, to make it easier for patients to coordinate the breath.

The Modulite platform was matched to its CFC counterparts on a microgram-for-microgram basis (using salbutamol pressurized MDIs and some corticosteroid pressurized MDIs), so no dosage modification is needed when switching from a CFC to a hydrofluoroalkaline formulation, Professor Dolovich said.

Breath-actuated pressurized MDIs have been developed to overcome the problem of poor coordination between pressurized MDI actuation and inhalation. Higher pulmonary disposition has been achieved with the Maxair Autohaler, a breath-actuated pressurized MDI, in patients who had poor coordination with a conventional CFC pressurized MDI, she said.

In another study, the onset of bronchodilation was similar between formoterol/ beclomethasone Modulite and formoterol/budesonide Turbuhaler (another breath-actuated pressurized MDI), and greater than with formoterol alone in patients with COPD, Professor Dolovich stated.

Nebulizers
The use of nebulizer therapy has been increasing. Nebulizers are typically used by patients who have difficulty operating pressurized MDIs or dry powder inhalers, because of poor hand–lung coordination.

Convention al nebulizers continuously release a drug throughout the respiratory cycle, so that as much as two thirds of the drug is wasted during expiration. They allow delivery of individual drug doses over a longer period than can be achieved with pressurized MDIs or dry powder inhalers, but to use a conventional nebulizer most efficiently, patients must be able to adapt to the device and have a regular breathing pattern.

Vibrating mesh nebulizers are a more recent development; they have a higher lung deposition, negligible residual volumes, and a faster rate of nebulization compared with jet nebulizers.

“Position of the nebulizer has been found to influence drug delivery,” Professor Dolovich said. In a study of the effect of nebulizer type and position on drug delivery, it was found that placement of the nebulizer before the humidifier increased drug delivery with vibrating mesh nebulizers and jet nebulizers, and that drug delivery with the vibrating mesh nebulizer was more than double that with the jet nebulizer at all positions.

Adaptive aerosol delivery systems have been designed to detect and constantly adapt to a patient’s variable breathing patterns. Software-driven monitoring and control systems monitor inspiratory flow and breathing frequency. The technology enables measurement of the volume of drug delivered per aerosol pulse, which ensures that the total preprogrammed dose is delivered.

Dry Powder Inhalers
Dry powder inhalers are breathactuated devices, and therefore do not require patient coordination, which is an advantage over pressurized MDIs. Newer designs for dry powder inhalers incorporate battery-driven impellers and vibrating piezoelectric crystals that reduce the need for patients to generate a high inspiratory flow rate, as with conventional dry powder inhalers.

Drug delivery into the lungs with dry powder inhalers is 10% to 37%; recent improvements in design permit the dose dispensed to be independent of inspiratory flow rate, at 30 L/min to 90 L/min. Variations in the design and performance of dry powder inhalers may make them not readily interchangeable.

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Last modified: February 14, 2019
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