Pharmaceutical Technology Chapter 6
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Questions and Answers

What are the two types of respiratory tracts?

Conducting and Respiratory

What are the 4 factors on which deposition of a drug/aerosol in the airways depend?

Physicochemical properties of the drug, formulation, delivery/liberating device, and patient (breathing patterns and clinical status)

What is the most important physical property of an aerosol for inhalation?

Particle Size

What is the formula to calculate aerodynamic diameter of a spherical particle?

<p>$da = dp \sqrt{\frac{\rho}{\rho_o}}$</p> Signup and view all the answers

When the particle size is 1- 5 µm, which deposition mechanism is most important?

<p>Gravitational Sedimentation</p> Signup and view all the answers

Which deposition mechanism is most important for particles smaller than 0.5 µm?

<p>Brownian Diffusion</p> Signup and view all the answers

Inertial impaction is a more important mechanism for deposition in the lower airways.

<p>False</p> Signup and view all the answers

What is the optimum breathing pattern for aerosol deposition?

<p>Slow, deep inhalations followed by breath-holding prior to exhalation</p> Signup and view all the answers

What are the 3 categories of nebulizers?

<p>Jet, Ultrasonic, and Mesh Nebulizers</p> Signup and view all the answers

What is the energy source for ultrasonic nebulizers?

<p>A piezoelectric crystal vibrating at high frequency</p> Signup and view all the answers

What are the disadvantages of cascade impactors or impingers?

<p>High flow rates and operating at constant air flow rates</p> Signup and view all the answers

Match the inhaler type with its description:

<p>Pressurized Metered-Dose Inhaler (pMDI) = Uses liquefied gas to propel medication in a fine spray Dry Powder Inhaler (DPI) = Delivers a preloaded powder dose, typically activated by patient inhalation Nebulizer = Produces a fine mist of medication for slow, continuous inhalation Spacer = A device used with pMDIs to improve deposition in the lungs, especially in children Breath-actuated pMDI = Releases medication only when the patient inhales Unit-dose DPI = Uses capsules or foil-covered blister pockets for single doses Multi-dose DPI = Contains multiple doses of medication in a preloaded device</p> Signup and view all the answers

Study Notes

Pharmaceutical Technology Chapter 6: Pulmonary Drug Delivery

  • Pulmonary Drug Delivery is a significant method for administering drugs.

  • Inhaled drug delivery offers several advantages, including:

    • Faster onset of action, compared to oral or parenteral administration.
    • Smaller doses required, leading to reduced systemic side effects and lower drug costs.
    • Improved bioavailability for drugs that aren't easily absorbed orally.

  • Local drug activity in the airways is used in treatment and prophylaxis of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis.

  • Systemic drug activity is also possible through inhalation, useful for:

    • Migraine treatment (ergotamine).
    • Insulin delivery.
    • Vaccine administration.
    • Growth hormone delivery.
    • Avoiding first-pass metabolism.

Lung Anatomy

  • Respiratory tract:
    • Conducting regions are responsible for air conduction (trachea, bronchi, bronchioles, terminal and respiratory bronchioles).
    • Ciliated epithelial cells and mucus in the conducting airways trap foreign particles.
    • Respiratory regions are responsible for gas exchange (respiratory bronchioles, alveolar regions).
    • Alveolar regions terminate in 2–6 x 108 alveoli (approx. 100-140 m2 surface area in adult males).

Inhalation Aerosols

  • Aerosol is a two-phase system of solid or liquid particles dispersed in a gas (e.g. air). Size is crucial for stability.
  • Deposition of drugs in the airways depends on four key factors:
    • Drug physicochemical properties.
    • Formulation of the drug.
    • Characteristics of the delivery device.
    • Patient-specific factors (e.g., breathing patterns, clinical status).
  • Particle size is critical, standardized by the aerodynamic diameter (da). For spherical particles, da = dp*(p/ρo), where dp is physical diameter, p is particle density, and ρo is unit density (1 g/cm3). The mass median aerodynamic diameter (MMAD) is a typical measure of particle size.
  • Large porous particles (∼20 µm) are delivered efficiently to the lungs due to low density and small aerodynamic diameter.
  • Humidity can affect particle size. Water-soluble materials can increase in size during high relative humidity via hygroscopic growth. This increase must be accounted for when calculating the deposition of the particles.

Particle Deposition in the Airways

  • Aerodynamic size > 5 µm results in deposition in the upper respiratory tract and mucocilliary clearance.
  • Aerodynamic size < 5 µm is required to reach the peripheral regions.
  • Aerodynamic size < 2 µm is preferred for alveolar deposition.

Deposition Mechanisms

  • Inertial impaction is significant for larger particles (>5 µm).
  • Gravitational sedimentation is crucial for particles (1-5 µm) in the small airways and alveoli.
  • Brownian diffusion is the dominant mechanism for small particles (< 0.5 µm).

Breathing Patterns and Particle Deposition

  • Patient factors like breathing pattern, lung physiology, and pulmonary disease influence particle deposition.
  • Larger inhaled volume leads to more peripheral distribution.
  • Higher inhalation flow rate results in deposition in larger airways via inertial impaction.
  • Breath-holding after inhalation facilitates sedimentation and Brownian diffusion.

Clearance of Inhaled Particles

  • Particles in the ciliated conducting airways are cleared by mucociliary clearance (within 24h).
  • Alveolar macrophages engulf insoluble particles and then remove them from the body via the mucociliary escalator or lymphatic system (days-weeks).

Devices for Pulmonary Drug Delivery

  • Pressurized metered-dose inhalers (pMDIs)
  • Dry powder inhalers (DPIs)
  • Nebulizers

pMDIs

  • Contain drug dissolved/suspended in a propellant.
  • Upon actuation, they release a metered spray dose.
  • Often use aluminum canisters, with a high-speed gas flow to disperse droplets.
  • Propellants: chlorofluorocarbons (CFCs) are now largely replaced with hydrofluoroalkanes (HFAs).
  • Formulation: pMDIs are usually formulated as suspensions of drug in propellants to prevent clogging and other formulation issues. Factors to consider include particle size of solid, relative solubility of API in propellant, use of surfactants.
  • Filling: cold filling and pressure filling methods exist.
  • Advantages: portable, low cost, disposable, reproducible doses. Protect drugs from degradation and contamination.
  • Disadvantages: inefficient drug delivery, potential for incorrect use by patient.

Spacers-actuated pMDIs

  • Designed to address pMDI disadvantages (e.g. poor inhalation/actuation coordination).
  • The use of spacers positioned between the pMDI and the patient.
  • A reservoir to minimize the initial droplet velocity.
  • Can address inappropriate use by the patient.

Breath-actuated pMDIs

  • Improved patient coordination issues.
  • Triggering medication delivery with inhalation.
  • Avoiding the bulk of spacers.

DPIs

  • Deliver drug as a dry powder.
  • Uses hard gelatin capsules, or foil blister discs.
  • Advantages: propellant-free, avoids excipient considerations.
  • Disadvantages: limited by patient inhalation.
  • Formulation: powders need micronizing and mixing with large carrier particles to aid in flow.

Multi-dose DPIs

  • Newer devices often have preloaded drug/carrier mixes.
  • Multi-dose DPIs (i.e. Turbuhaler®): designed as reservoir type inhalers delivering a larger number of doses. They can run into issues concerning humidity if they are not carefully sealed.
  • Other multi-dose DPIs (e.g. Accuhaler® , Diskhaler®) can be easier to use (e.g. fewer actions by patient required).

Nebulizers

  • Used for larger doses of drug solutions or suspensions.
  • Useful for children and elderly.
  • Jet, ultrasonic, and mesh nebulizers are different types.
  • Formulation: nebulized fluids are typically aqueous solutions. Co-solvents (e.g. ethanol) and surfactants can be used.
  • Considerations: viscosity, surface tension.

Size Analysis of Aerosols

  • Methods for analyzing aerosols characteristics. Important for determining how much aerosol reaches the target area.

Cascade Impactors and Impingers

  • Used to measure aerosol.
  • Comprise multiple stages to capture aerosols at different aerodynamic sizes.
  • Disadvantages: can lead to solvent evaporation due to high flow rates, particles bouncing off the collection chamber.

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Pharmaceutical Technology Chapter 6 PDF

Description

Explore the intricacies of pulmonary drug delivery in this quiz based on Pharmaceutical Technology Chapter 6. Learn about the advantages, local and systemic drug activities, and the anatomy of the lungs related to inhaled therapies. This chapter highlights its critical role in treating respiratory diseases and beyond.

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