Aerosols in Medicine

Aerosols

• Aerosols are a fine dispersion of liquid or solid particles in a gas, where particle size is less than 50µm. Examples include mists and smoke.
• Therapeutic aerosols are used for applying medication to external body surfaces, or accessible body cavities like the mouth and nose. They are also sprayed onto protective films for wounds and burns.
• Common active ingredients include antiseptics, antibiotics, local anaesthetics, dermatological steroids, and bronchodilators.

Advantages of Aerosols

• Convenient, fast, and easy application.
• Efficient dispersion of the medication.
• Avoids direct manual contact with the medication, protecting both the medication and the patient.
• Provides immediate, localized application.
• High concentration of medication in a limited area is achieved.
• Minimizes irritation to sensitive areas.
• Rapid response to medication.
• Controlled and uniform dosage via metered valves.
• No product contamination from the environment.
• Protects light-sensitive (photolabile) drugs.
• Prevents oxidation and hydrolysis.
• No first-pass effect when administered via oral inhalation.

Disadvantages of Aerosols

• Costly due to expensive containers, valves, propellants, and filling methods.
• Can be difficult to dispose of properly.
• Heat susceptibility; pressure build-up can occur.
• If the drug in question exhibits insolubility when combined with the chosen propellant, it necessitates the use of co-solvent emulsions or suspensions to achieve an effective delivery system. This requirement increases the complexity of the formulation process, as careful consideration must be given to the compatibility and stability of all components involved.
• Propellant toxicity, especially with long-term use, exists.
• The cooling sensation produced by volatile propellants can cause discomfort or pain when applied to already injured or sensitive skin, potentially exacerbating the condition rather than providing relief.
• Necessary to test formulation compatibility with all container and valve parts.
• Aerosol systems can potentially pose an environmental hazard.
• Faulty valves or spray systems can render the product useless.

Aerosol Systems

• Two-phase systems: contain a liquid phase (propellant or propellant mixture with the active ingredient in solution - could form a foam), and a vapour phase (propellant vapor). Propellant vapor pressure is high, pressurizing the container. When the valve is depressed, the pressure forces the liquid into the atmosphere, causing the propellant to vaporize and disperse the active ingredient. If the active is insoluble, a co-solvent like ethanol can be used thus affecting the vapor pressure.
• Three-phase systems: involves a solution of the active ingredient in a suitable solvent immiscible with the propellant. The system has distinct propellant liquid phase, solution liquid phase, and a vapour phase. The propellant's position (lighter or heavier than the solution) affects the necessary modifications to the dip-tube to avoid propellant spraying.

Propellants

• Propellants need specific properties: low toxicity, non-flammable and non-explosive, odorless and colorless, good solvents, non-irritating, and relatively inexpensive.
• Propellant types include liquefied gases like fluorinated hydrocarbons (e.g., fluoromethanes) and hydrocarbons (e.g., propane), and compressed gases (insoluble, like nitrogen, and soluble, like nitrous oxide).

Containers

• Container selection criteria include mechanical strength, chemical inertness, and cost.
• Glass containers, especially when reinforced with plastic films to enhance durability, are ideal for low-pressure applications. They offer excellent chemical resistance and transparency, allowing for easy monitoring of contents while minimizing contamination risks.
• Stainless steel is expensive but withstands high pressures well; it's virtually non-corrosive.
• Tin-plated steel is a cost-effective option that can be made non-reactive using suitable plastic coatings.
• Steel containers typically consist of three distinct parts: a cylindrical body that holds the contents, a top that secures the container, and a bottom that provides stability and durability.
• Aluminum containers, which are typically produced in two-piece or mono-bloc designs, are renowned for their ability to withstand high internal pressures. These containers are lightweight and highly resistant to corrosion, making them suitable for various applications, including those that involve storing gases or liquids under pressure, ensuring both safety and efficiency.
• Glass containers are often molded to fit specific types of valves for low pressures.
• Plastics, like acetal resins and polypropylene, are suited to high-pressure applications.

Valves, Dip Tubes & Actuators

• Valve type depends on the product's formulation and application.
• Different valves exist for sprays, foams, and delivering individual doses.
• Metering valves control the amount of product released into a chamber.
• Precise product emptying employs polyethylene/polypropylene dip tubes which connect to the valve and extend the entire length of the container.
• Valve actuators are specially shaped to facilitate easy application to specific body areas, providing a desired product and propellant droplet size.

Basic Aerosol Formulation

• Formulation depends on the active ingredient's solubility in the propellant.
  • If the active is soluble, it dissolves directly into the propellant or propellant mixture and propellant ratios are adjusted to achieve the desired pressure.
  • When dealing with active ingredients that are insoluble in water but can be dissolved in a co-solvent, it is essential to utilize solvents such as ethanol as an effective medium for solubilization. The ratio between the co-solvent and the propellant is crucial, as it directly impacts the formulation's stability, efficacy, and ability to deliver the active ingredient effectively when applied or sprayed. Careful adjustments to this ratio can lead to optimal performance.
  • If the active is insoluble in both propellant and co-solvent, but soluble in water (H₂O), it can be formulated in an aqueous solution with the propellant, which can also be introduced into the system, or it can be formulated as an emulsion.
• If the active ingredient is an insoluble solid, it must be suspended in the propellant at a specific particle size, typically ranging from 5 to 10 micrometers (µm). This size range is crucial for ensuring that the particles remain evenly dispersed in the aerosol mixture, thus providing consistent delivery and optimal therapeutic effect upon application.

Factors Affecting Spray Characteristics

• Viscosity affects particle size; higher viscosity means larger particles and a wetter spray; lower viscosity means smaller particles and a finer spray.
• Propellant vapour pressure impacts particle size; higher pressure result in finer sprays.
• Propellant-product ratio: higher propellant ratio generally creates a finer, drier spray.
• Solvents can affect pressure, influencing the spray.
• Temperature changes affect vapor pressure and spray.

Testing of Aerosols

• Manufacturing processes use inline leakage testing - immersed in hot water to detect leaks.
• Internal pressure measurement uses a pressure gauge.
• Spray pattern assessment is based on pressure, viscosity, and product/propellant ratios, and visually examined.
• Discharge rates inform on the number of operations to empty a container.
• Flammability test is performed.
• Particle size analysis utilizes cascade impaction tests.
• Phase Doppler Anemometry may be used to measure laser beam scattering from particles.
• Moisture content is checked for its impact on metal corrosion and degradation of certain drugs.
• Propellant mixture analysis uses gas-liquid chromatography.

Dry Powder Inhalers (DPI)

• Fine drug powder is mixed with an excipient (e.g. lactose). The mixture is housed in a hard gelatin capsule.
• Excipient particle size is larger than the drug to prevent it from entering the airway.
• When the capsule is opened, a turbulent airflow disperses the powder which is inhaled.

Advantages and Disadvantages of DPI's

• Advantages:*
• No hand-breath coordination is needed.
• Environmentally friendly.
• Can deliver proteins/peptides.
• Disadvantages:*
• More expensive than Metered Dose Inhalers (MDIs) are widely used devices for delivering medication directly to the lungs through aerosolized sprays. They are commonly employed in the management of respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD). MDIs allow patients to inhalatively receive precise doses of medication, ensuring optimal therapeutic outcomes. The design typically features a canister containing the drug formulation, combined with a propellant that helps to create a fine mist for inhalation. Proper technique is crucial for maximizing drug delivery and effectiveness.
• Requires frequent refilling.
• Loose powder makes the device messy and can cause coughing.
• Reliance on inspiratory effect to disperse the aerosol.
• Variable performance among patients and across different days.

Nebulisers

• Devices employed for aerosolizing drug solutions into inhalable mists include

• Ultrasonic Nebuliser are an effective means of delivering aerosolized medication directly to the respiratory tract. These devices provide a method for patients who may struggle with puffs or sprays, ensuring deeper lung penetration.

• Jet nebulizers are medical devices used to deliver medication in the form of a mist, allowing it to be inhaled directly into the lungs.

• These devices operate by using a jet of compressed air or oxygen to create an aerosolized mist from a liquid medication solution. The mechanism involves a jet nozzle that draws in the liquid, and the energy from the air stream breaks the liquid into fine droplets suitable for inhalation. Jet nebulizers are commonly used for patients with respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, as they provide the ability to deliver larger doses of medication compared to metered-dose inhalers (MDIs).

  Advantages and Disadvantages of Jet Nebulizers

  • Advantages:

    • Effective for high doses of medication.
    • Can be used with a variety of medications, including those that are not suitable for MDIs.
    • Suitable for patients who may have difficulty using inhalers, such as children or the elderly.

  • Disadvantages:

    • May be less portable compared to inhalers.
    • Requires a power source, limiting use in certain settings.
    • Cleaning and maintenance are necessary to prevent contamination and ensure proper functioning.

  , which use compressed air to generate a mist for inhalation.

Ultrasonic Nebuliser

• An ultrasonic nebuliser utilizes an electrically powered transducer that generates high-frequency vibrations, effectively transforming the drug solution into tiny aerosolized droplets. These small particles are essential for efficient inhalation therapy, as they can easily penetrate deep into the lungs, ensuring maximum drug delivery and therapeutic effects. This type of nebuliser is particularly valuable in the treatment of respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD).
• One significant advantage of ultrasonic nebulisers is their quiet operation, which makes them more comfortable for patients, especially children. However, they do rely heavily on an electric power source, which poses a risk of overheating during extended use and necessitates careful monitoring to prevent malfunction.

Jet (Air-blast) Nebuliser

• A compressed gas stream (jet) generates a negative pressure, inducing liquid from the reservoir into the jet, atomising it into smaller droplets.
• Coarse droplets are collected while smaller droplets are inhaled.

Advantages of Nebuliser Therapy

• Large bronchodilator doses are possible.

• Hand-breath coordination is not a requirement when using jet nebulizers. This feature enhances convenience, as patients do not need to synchronize their inhalation with the device's operation.

• Issues concerning propellant sensitivity are avoided using solutions like Isotonic saline -is a sterile solution that contains 0.9% sodium chloride (NaCl) in water, which is equal in concentration to human body fluids. This makes it an essential component in various medical applications. It is commonly used for intravenous (IV) infusions and to maintain or restore fluid balance within patients.

  In the context of respiratory therapy, isotonic saline can be nebulized to help hydrate and thin mucus in patients with conditions such as asthma or cystic fibrosis, making it easier to expel mucus.

• Vehicle solution (normal saline) has additional positive effects (soothing airways and liquifying secretions).

Explore the fascinating world of aerosols, their definitions, applications, and advantages in medicinal use. This quiz covers therapeutic aerosols and their active ingredients, focusing on how they facilitate medication delivery efficiently. Test your knowledge on this essential aspect of modern medicine.