W5 Pulmonary Drug Delivery l ll and lll Flashcards

Question

Drug in hard capsule DPIs

Answer 1

* Drug (+ carrier) is loaded into a hard-shelled gelatin capsule * Capsule is loaded into the device by the patient * Punctured by two metal needles inside the device * Inspiration by the patient causes a rotor to rotate and this causes a turbovibratory air pattern to disrupt the powder in the capsule

Answer 2

1. Multiple unti dose device * Diskhaler and Accuhaler 2. Reservoir based device * Turbohaler and Clickhaler * – Multiple unit dose device – Reservoir-based device

Answer 3

Smart inhalers use sensors in the device to detect and record on the use of the inhaler * The inhaler connects via Bluetooth to a smartphone or other device and (should the patient choose to) their data can be shared with the prescriber/ asthma specialist * GoResp Digihaler (Teva) was launched in the UK in July 2023 * DPI containing budesonide (steroid), formoterol fumarate dihydrate (long-acting β2-agonist) * Data gathered can include: – How often the device is use – Inspiratory flow rate (important for a DPI)

Answer 4

* Nebulizers are much larger pulmonary delivery devices that generate aerosols from the contents of unit dose nebules * Large volumes of drug solution (and therefore doses) can be administered * Drug inhaled during normal breathing usually via a mask * Nebulizers are used in hospital and domiciliary settings * Generally not very portable due to their size and power requirements Nebulizers Nebule contents emptied into nebulizer and inhaled over an extended time period A nebulizer mask (James Heilman MD)

Answer 5

* Nebule formulations can be quite simple and are often just the drug dissolved in “normal saline” * Normal saline is a 0.9% w/v NaCl aqueous solution * Can be a solution or suspension Saline-based nebules can also usually be diluted with normal saline if required

Answer 6

1. Jet Nebulizers 2. Ultrasonic Nebulizer 3. Mesh Nebuliser

Answer 7

* These require compressed air from a cylinder, hospital air line or electrical compressor Jet Nebulizers Jet nebulizer (adapted from Aulton’s Pharmaceutics) Compressed air passed through the Venturi nozzle – low pressure created draws liquid up from the reservoir through a feed tube Baffle ensures that (larger) non- respirable particles are not inhaled and can be recycled Aerosol out Aerosol droplet size and drug delivery is determined by the compressed gas flow rate

Answer 8

Energy to generate aerosol comes from a vibrating piezoelectric crystal Large aerosol droplets are emitted from the apex and smaller droplets from the lower areas

Answer 9

* These are more recently developed devices and involve aerosol being generated by a vibrating mesh * Mesh (perforated plate) may have up to 7000 holes etched with a laser Vibrational energy due to a piezoelectric crystal which transfers energy to the mesh via a transducer Newer designs are able to coincide aerosol release with the patient’s breathing= reducing drug wastage

Answer 10

* Pfizer’s Exubera dry powder insulin formulation was launched in the UK in 2006 (but withdrawn in 2007) * Significant challenges overcame including the development of an insulin formulation stable at room temperature * Insulin deagglomerates in the chamber prior to inhalation * Referred to (in Aulton) as a breath-assisted DPI * Compressed air generated by movement of the handle on the device * Sanofi launched MannKind’s Afrezza inhaled insulin device in 2015 (“withdrawn” in 2016) * Another dry powder formulation: insulin + Technosphere aggregates (2 – 5 m) which rapidly dissolve in the lung * Overcame some of the issues with Exubera but 25% of all Afrezza® users experienced cough and sales were ultimately disappointing

Answer 11

AER-501 is a liquid formulation of human insulin and is inhaled using a small, smart inhalation device * Similar principle to that of a mesh nebuliser, i.e. vibrating mesh technology Pulmonary delivery for a systemic effect AER-501 is delivered with the AFINA Inhaler Image from AERAMI Therapeutics Liquid insulin formulation is added dropwise (by the patient) into the inhaler

Answer 12

* In widespread public usage and MHRA have recently published guidance for licensing electronic cigarettes * Multiple designs available (disposable / refillable) * Formulation: cartridge typically contains nicotine, propylene glycol, glycerine (glycerol), flavourings Aerosols contain fewer numbers (and lower levels) of toxicants than cigarettes Evidence emerging that usage indoors increases concentration of nicotine / particulate matter in the air

Answer 13

* Medical gases may be delivered in cylinders or generated in situ, e.g. using an oxygen concentrator * Hospital uses and domiciliary care * Oxygen gas is under pressure in a cylinder and the flow is controlled with a regulated tap (central pipelines often used) * Continuous positive airway pressure ventilation (CPAP) – O2 enriched air delivered via mask/ hood/ nasal cannula * Ventilator – machine that helps with breathing; air or O2 enriched air delivered via a breathing tube

Answer 14

* Scintigraphy = radiation emitting substances are administered to a patient and the subsequent emissions are captured by a gamma camera and an image produced Lung scintigraphy can be used as a diagnostic tool and also to evaluate new respiratory formulations * Diagnostic: patient inhales nebulized radionuclide-containing solution and/or has radiopharmaceutical injected iv * Formulation: drug-carrier aggregates are radiolabelled (Tc99m) and loaded into the device. Participants would inhale from the device and deposition of drug would be imaged (can assess bioavailability)

W5 Pulmonary Drug Delivery l ll and lll Flashcards

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