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Pulmonary drug delivery

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Pulmonary drug delivery

Pulmonary drug delivery is a route of administration in which patients use an inhaler to inhale their medications and drugs are absorbed into the bloodstream via the lung mucous membrane. This technique is most commonly used in the treatment of lung diseases, for example, asthma and chronic obstructive pulmonary disease (COPD). Different types of inhalers include metered-dose inhalers (MDI), dry powder inhalers (DPI), soft mist inhalers (SMI) and nebulizers. The rate and efficacy of pulmonary drug delivery are affected by drug particle properties, breathing patterns and respiratory tract geometry.

Pulmonary drug delivery minimizes systemic side effects and increases bioavailability owing to the localised absorption through the lung. The disadvantages include possible drug irritation to the lung, limited drug dissolution, relatively high drug clearance, and the drug effectiveness depends on the inhaler techniques and patients' compliance. Drug formulation can be challenging since the drug has to bypass the defence mechanisms in the respiratory tract. Pharmacokinetics and pharmacodynamics of the drug in elderly patients can also be particularly difficult to predict due to age-related changes in body composition.

Ongoing developments in inhaler device engineering, technology and drug formulations may improve the efficacy and overcome the challenges of pulmonary drug delivery. Recent advancements involve the utilization of the pulmonary route as an entry to systemic circulation for treating different diseases, as well as the development of pulmonary drug formulation and particle engineering technology to increase the efficacy of pulmonary delivery.

Pulmonary drug delivery is mainly utilized for topical applications in the lungs, such as the use of inhaled beta-agonists, corticosteroids and anticholinergic agents for the treatment of asthma and COPD, the use of inhaled mucolytics and antibiotics for the treatment of cystic fibrosis (CT) and respiratory viral infections, and the use of inhaled prostacyclin analogs for the treatment of pulmonary arterial hypertension (PAH).

In addition, this technique is employed for systemic application, for example the use of inhaled insulin for diabetes management, the use of inhaled loxapine for treatment of psychiatric disorders. Vaccines, such as the measles-rubella vaccines, can also be delivered via inhalation.

Metered-dose inhalers include pressurized metered-dose inhalers (pMDIs) and breath-actuated metered-dose inhalers (BAMDIs). pMDIs are the most commonly used inhalers for treating lung diseases. It requires coordination of patients' inhalation and inhaler actuation. BAMDIs are triggered by patients' inspiratory flow instead of hand actuation, solving the coordination issue. MDIs with spacers have similar effectiveness in drug delivery compared to nebulizers, with additional benefits in convenience and cost-effectiveness. The use of MDIs together with spacers, valved holding chambers (VHCs) or masks improve the efficacy of drug delivery into the lungs.

The solid drug powders in DPIs are released by the force of the patient's inspiratory flow. Turbulent airflow generated inside the inhaler by the inhalation force is associated with the movement of airflow and the resistance inside the inhaler. Patients should inhale with adequate inspiratory flow to overcome the resistance of DPIs, leading to drug particle deaggregation for successful pulmonary delivery.

Soft-mist inhaler aerosolized a fixed dose of liquid drug formulation into inhalable tiny particles through an extremely fine nozzle system using the energy generated by the lever-compressed spring, without the use of propellants. The slow and prolonged duration of aerosolization facilitates the patient's coordination between inhaler actuation and inhalation.

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