Inhalation Devices and Metered-Dose Inhalers (MDIs)

• Inhalation devices are used to administer medication directly into the lungs.
• Pharmaceutical aerosols are pressurized dosage forms emitting a fine liquid or solid dispersion containing active ingredients in a gaseous medium.
• Pharmaceutical aerosols differ from other dosage forms because they depend on the container, valve assembly, and propellant.
• Upon valve opening, the propellant expands and evaporates, forcing the content out as a fine mist or powder spray.
• Three commercially available types of pulmonary drug delivery devices are pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), and nebulizers.
• Pulmonary drug delivery devices include different types of inhalers and nebulizers.

Metered-Dose Inhalers (MDIs)

• pMDIs are the most popular inhalers for treating local respiratory diseases like asthma and COPD.
• Structural components of a conventional pMDI include a canister, metering valve, actuator, and mouthpiece.
• The drug is either suspended or solubilized in a propellant formulation within a canister/valve assembly.
• Actuation through the metering valve causes rapid expansion of the propellant, generating aerosol droplets.
• A pressurized canister contains the medication and attaches to a delivery device, releasing the drug as an aerosol cloud upon pressing down.
• Uncoordinated use can occur if actuation coincides with exhalation.
• Advantages of pMDIs include being small, portable, inexpensive, convenient, and suitable for a wide range of drugs.
• Disadvantages include requiring good coordination and technique.
• The actuation force/breath coordination is unsuitable for elderly or pediatric users, leading to high oral deposition and a limited dose per actuation.
• The cold Freon effect can lead to coughing and discomfort.
• The cold Freon effect is a sensation caused by the rapid expansion of the propellant, leading to coughing and discomfort.

Breath-Actuated MDIs

• Breath-actuated MDIs sense the patient's inhalation through the actuator, synchronizing dose delivery.
• Synchronization can be achieved via add-on devices (inhalation aids).

Spacers

• Spacers are tubes or extensions placed between the patient and the pMDI.

Valved Holding Chambers (VHCs)

• VHCs have a one-way valve at the mouthpiece end, allowing inhalation and preventing exhalation into the chamber.
• VHCs help patients breathe from a "standing aerosol cloud" without breath coordination.
• The inhalation flow rate is coordinated through the actuator, enabling reliable PMDI actuation during inhalation (e.g., Easibreathe).
• Advantages of breath-actuated pMDIs include reduced oropharyngeal deposition and increased deep lung deposition, optimal performance, and reduced cold Freon effect.
• Users of MDIs may experience the cold Freon effect, an unintentional reaction characterized by coughing or a chilling sensation.
• The cold Freon effect is due to the impaction of the delivered dose and rapid evaporation of any remaining propellant, significantly influencing drug delivery efficiency.

Dry Powder Inhalers (DPIs)

• In DPIs, medication is in dry powder form.
• The drug mixes with a coarser excipient to which it attaches.
• Passive DPIs aerosolize dry powder formulations solely by patient inspiration, accounting for over 90% of pMDI misuse.
• Individual particles are deagglomerated by external forces such as airflow shear, particle interactions, and particle-device impact.
• Examples of DPIs include Clickhaler, Multihaler, Diskus, Gyrohaler, Duohaler, and Aspirair.
• Feed powder into a high-speed airflow to split particle agglomerates, achieving respirable particles.
• The drug delivery through DPI is highly dependent on inspiratory flow rate due to strong interparticle forces.
• Rapid airflow increases oropharyngeal deposition and reduces lung dose; not suitable for patients with breathing difficulties; moisture uptake can cause stability issues; relatively high cost.

Classification of DPIs

• DPIs are classified by the number of doses, aerosolization, or powder dispersion mechanisms.

By Number of Doses

Single-Unit Dose DPIs

• Doses are pre-measured and supplied in individual capsules, loaded by the patient before use.
• Single-unit dose DPIs can be disposable or reusable.

Multi-Unit Dose DPIs

• Use factory-metered and sealed doses packaged for multiple doses without reloading.
• Packaging includes replaceable disks, cartridges, or foil-polymer blister packaging.

Multi-Dose (Reservoir) DPIs

• Store powder in bulk and use a built-in mechanism to meter individual doses upon actuation.
• Challenges include dependence of emission on flow rate and moisture uptake.

DPIs Based on Aerosolization Mechanism

• DPIs can be classified as passively or actively-actuated.
• The first passive DPIs were the Rotahaler and the Spinhaler, which are single-dose devices.
• A capsule containing the powder dose is loaded into the Rotahaler. Upon actuation, the capsule is pierced, and an impeller rotates the powder, releasing it from the capsule via the inspiratory force of the patient
• In Spinhalers, the capsule splits into two halves, releasing the dry powder when. the patient inhales.

Active DPIs

• .Some DPIs actively generate the aerosol, reducing dependence on patient -inhalation while improving. active DPI's are usefyl when the patients inh.cap. is compromised.
• Assistance can be vibrations generated by a piezoelectric transducer
• For example, Has a battery-powered motor that disperses powder by impaction of a rotating impeller to generate aerosol from the powder bed. The motor is activated by a very low breathing rate

DPI & Particle Deagglomeration

• To aerosolize drug powder, individual particles must be deagglomerated by external -forces such as:

-Airflow shear

• Particle-particle interactions

• Particle-device impaction

• Devices that is high-speed use airflow

• Devices that rely on particle impaction for deagglomeration: Spinhaler

Active DPI - Limitations

• Due to strong interparticle, drug delivery of DPI highly dependents on inspiratory flow rate.
• Rapid airflow chances of increases oropharyngeal deposition and reduces the dose to the lungs
• Relatively high cost

Active DPIs (Spiros™™)

Some DPIs actively generate the aerosol, reducing dependence on patientinhalation while improving accuracy and reproducibility of the delivered dose. Assistance normally comes in the form of:

• Pressurized/compressed air
• Vibrations generated by a piezoelectric transducer

Nebulizers

• Nebulizers convert a liquid into aerosol droplets to produce a respirable cloud suitable for inhalation, using compressed air or ultrasonic power.
• Nebulizers convert a liquid into aerosol droplets, which is great for using in hospitals.

-Features:

• Little to no coordination is needed.

• loaded w/formulation bef. each treatment & operates afters its loaded

• Advantages:

• Little or no coordination

Use for:

• Pediatric, the elderly, ventilated ,and non-conscious patients.
• • Imp. aerosol performance,delivery efficiency

Disadvantages:

• Cumbersome
• Bulkier and require longer administration time.

Types of Nebulizers

Jet Nebulizers

• Jet Nebliziers Is based on Venturi"s principle, , which states that fluid pressure decreases as it passes through a narrow sectional area
• Air stream moves through a small capillary tube drives the liquid to be aerosolized up the capillary tube

Ultrasonic Nebulizers

• Vibrating piezoelectric crystal, which generating sound wave that break the liquid into small aerosol droplets

Vibrating Mesh Nebulizers

• Use ultrasonics to generate droplets that are pushed through a static or vibrating mesh or plate to form a cloud prior to inhalation

Features of Respimat® Soft Mist™™ Inhale

• Combines a pMDIs and Nebulizers

key feature: Small Aerosizes propel-free drug solution as a soft mist, reduction orophraygeal deposition. spring mechanism to push liquid generating a slow mist over 1-1.5

Advantages of Respimat® Soft Mist™™ Inhaler

Not dependat on insp. effort Lung deposition avg is over 40+ Drug is in solution ,shaking not requires has Some coordination of actuation and inspiration, which limit use in Very young children

Overview of inhalation devices for pulmonary drug delivery, focusing on metered-dose inhalers (MDIs). Discusses pharmaceutical aerosols, their components, and how they work. Explores structural components of pMDIs like canister, metering valve, actuator, and mouthpiece.