Devices for pulmonary drug delivery

Devices for pulmonary drug delivery

Pulmonary drug delivery almost invariably requires aerosolization of the drug using a device or mechanism that can achieve controlled drug particle formation and delivery. Examples of devices that have been used for pulmo-nary delivery include the following:

1. Metered dose inhaler: Pressurized spray is a metered dose inhaler (MDI) that incorporates propellant(s), surfactant(s), and the drug in either dis-solved or suspended state in its formulation. Pressurized metered dose inhalers provide constant pressure on the liquid formulation and con-sistent quantity of drug release on actuation of the valve. The propel-lants used in these formulations include chlorofluorocarbons (CFCs) and hydrofluoroalkanes (HFAs). Effective use of an MDI requires patient coordination of breathing and actuation to provide maximum amount and flow velocity of air going into the lungs. Drug solubility, vapor pressure, surface tension, solubility of oxygen/hygroscopicity, and density affect the effectiveness of drug delivery through the MDIs. MDIs are commonly used for the delivery of drugs for asthma and chronic obstructive pulmonary diseases (COPD).

2. Nebulizer: The nebulizer uses an air compressor as a power source instead of a liquid propellant. Compressed air is brought in contact with an aqueous solution of the drug in a device. Liquid shearing leads to the formation of drug droplets that get inhaled by the patient. Droplet size is a key factor in effective pulmonary delivery of the drug through this route. The droplet size is typically controlled through the orifice diameter of the baffle, pressure of the gas, and the density, con-centration, viscosity, surface tension, and flow rate of the drug solu-tion. Nebulizers are frequently used in applications where patient’s strong inhalation is not required for effective drug delivery such as in pediatric or hospitalized patients.

3. Dry powder inhaler: The dry powder inhaler (DPI) allows the drug to be formulated in dry state, in which it may be more stable, does not require the use of a liquid propellant, and also does not require patient coordination between breathing and actuation. DPIs consist of a sus-pension of fine particulate drug formulation, which is dispersed by mechanical, pneumatic, or electrical energy, or by the strength of the vacuum generated by the patient’s breathing. DPIs have been used to treat diseases such as asthma, bronchitis, emphysema, and COPD.

Optimization of particle properties and device parameters can increase drug penetration to the lungs. For example, simulation results of hydroflu-oroalkane (HFA)-propelled metered dose inhaler (pMDI) show increased droplet transport and deposition to the lungs when used with a spacer (Figure 15.1). This study illustrates the impact of a simple spacer in terms of enhanced droplet percentage reaching the tracheobronchial tree.

For further discussion and details on the devices used for pulmonary drug delivery, see Chapter 24.

Figure 15.1 Drug delivery to the lung. Role of device in enhanced drug penetration into the lung. Simulation results of hydrofluoroalkane (HFA)-propelled metered dose inhaler (pMDI) droplet transport and deposition: (a) without and (b) with spacer, illustrating the impact of a simple spacer in terms of enhanced droplet percentage reaching the tracheobronchial tree. Q = Airflow Rate. (Courtesy of Annual Reviews, Palo Alto, CA.)