TD: Pulmonary Delivery Flashcards
Describe the respiratory anatomy
- Large surface area – 100m2, 70m2 of which is in contact with capillaries (2000km).
- Each lung contains around 300 million alveoli.
- Large SA for gas exchange and durg delivery
- Small molecules can be absorbed within seconds.
- Avoids first-pass metabolism.
- pH 6.6, 99% relative humidity.
- Blood flow is elevated at 5 L/min.
- Lungs lined with fluid, 15-70ml.
- Mucociliary escalator, especially insoluble and >6µm.
- Mucus traps and cilia sweep up respiratory tract away from lungs
- Particles 1.5-3µm phagocytosed.
Describe the pulomary circulation
Advantages of the pulmonary route
- Bypasses the first-pass effect, some local degradation.
- Smaller dose required, fewer side effects.
- Non-invasive.
- Rapid onset of action.
- Local or systemic action.
Disadvantages of pulomary route
- Poor bioavailability – 8%.
- Poor technique
- Hitting back of throat
- Due to particle size requirement
- Specific particle size limits
- Rudimental bioavailability testing.
- Training required for device technique.
- Some drugs can cause oral thrush.
- Rinise mouth after using
- Lactose commonly used as a carrier –
- adhesive enough for stability, weak enough for drug release.
- Lactose intolerent?
- Some devices are bulky to carry.
- Some devices require coordination.
Common respiratory diseases?
- Asthma
- COPD
- Chronic bronchitis
What are examples of inhalers available?
- MDI
- DPI
- Nebuliser
Describe MDI inhalers?
What excipents are required?
What must the patient have to use this?
- Particle size reduced drug suspended in propellant (HFA): up to 200 doses per canister.
- Pressurised canister.
- Cosolvent, surfactant, stabiliser
- Good technique required for successful drug delivery.
- Spacer can be used
What types of DPI devices are available?
- Single unit dose
- Multiple unit dose
- Multidose
What are DPI considerations
- Particles must be within 1-5µm (dry).
- Moist lung environment enlarges particles.
- Phagocytosis occurs when particles are 1.5µm-3µm.
- Gravity ceases to be the largest force at this size.
- Static electricity can be a real problem during manufacture and handling.
- Require an inert carrier.
What types of nebulisers are available?
What is advantages and disadvantages of nebulisers?
- Pneumatic, ultrasonic or mechanical
- Large volumes.
- No coordination required.
- Useful for children and elderly.
- Large and bulky devices however
What are manufacturing consideration points for inhalers?
- Propellants.
- Static electricity.
- Particle size.
- Too large and hit back of throat, or swept up by mucus and cilia
What device is used to test inhalers and how does it work?
Andersen Cascade impactor:
Aluminium ‘lung’ which inhaler attached too. Chambers get increasingly smaller and tests how far drug travels down. Drug may get stuck on silica linning plates and will bounce and bash around.
Counseling points for inhalers
- Remove protective cap.
- Shake before use.
- Keep upright during use.
- Tight seal around mouthpiece.
- Inhale slowly and deeply.
- Hold breath for 10 seconds after inhalation.
- Wait 1 minute before next dose.
- May need to coordinate breath and device actuation.
- Rinse mouth afterwards if using steroids.
What is a useful device for patients and what is it used for?
In-check dial inhaler trainer device - shows patirents the required inwards strength of breath required for inhaler
- Less than 20% of the total dose is delivered to the lung.
- Patients can achieve peak inspiratory flow rates of between 30-180 L/min.
- Lower end will not produce the same particle sizes as the middle or higher end of the range.
- Every formulation has a different size profile.
Current and future challenges
Systemic drug delivery – Afrezza FDA approved.
Propellants.
Biopharmaceuticals.
Controlled release – polymers, accumulation?
