Pulmonary Drug Delivery Lecture Notes PDF

Pulmonary Drug Delivery iStockPhoto via University of Minnesota  Next week Bring your calculators to follow along! Chapter 21 in Ansel. 16th addition  Objectives Be able to explain how the droplet size and settling velocity affects drug disposition Under...

Pulmonary Drug Delivery iStockPhoto via University of Minnesota  Next week Bring your calculators to follow along! Chapter 21 in Ansel. 16th addition  Objectives Be able to explain how the droplet size and settling velocity affects drug disposition Understand the major differences in regards to the ingredients of MDI’s vs DPI’s Understand what the 3 USP section’s provide guidelines on. Patient factors that can affect the deposition of droplets within the respiratory tract  Understand how viscosity and surface tension of an ophthalmic products (and intranasal) affects residence time and drug absorption.  Know the acceptable pH, the isotonicity ranges (if mentioned) of ophthalmic and intranasal product. Understand isotonicity as it relates to the eye and all of the dosage forms.  MDI, DPI, Nebulizers, Spacers: know all of the advantages, disadvantages and characteristics.  Rationale Ancient civilizations, current smokers and drug abusers know that inhaled drugs: – Act quickly – Minimize the dose required – Are non-invasive Scientist and physicians later discovered that inhaled drugs: Go directly to the lung Minimizes side effects Avoids hepatic first-pass metabolism Are systemically absorbed  Advantages of Respiratory Drug Delivery for Local Effect Delivery to site of action (where local effect is required) Lower doses required (because of the ). Reduction of systemic side effects Large surface area* Rapid onset (some asthma meds) Avoids GI upset Avoids first-pass metabolism Lung offers a less hostile environment to most drugs including proteins and peptides.  Disadvantages of Respiratory Drug Delivery for Local Effect Dose estimation and dose reproducibility are difficult. Many variables. Guidance and technique on how to proper use is required* Mucus and infection may impede drug deposition to the lower airways. The physical stability of pharmaceutical aerosols may be problematic. + these if effect is systemic: Absorption limited by the mucous layer. Mucociliary clearance reduces the retention of drugs in the lungs (this is not good in poorly soluble or slow absorbed).  Respiratory Tract The lower respiratory tract, comprising: trachea, dividing into: bronchi, dividing into: bronchioles, dividing into: alveoli. –gas exchange with the  Factors affect Drug Deposition in the Lung The physicochemical properties of the aerosolized droplets or particles containing the drug Physiological and anatomical considerations The delivery device  Physicochemical Factors In pulmonary drug delivery, the inhaled particles need to settle on lung tissues. – This means that both the diameter and density are important to factor in. Mean Aerodynamic diameter (MAD): the diameter of the unit density (density = 1 g/cm3) sphere that has the same settling velocity as another particle. So, if an irregular shaped particle has an aerodynamic diameter of 5 microns, it means its terminal settling velocity is equal to a 5-micron spherical particle with a density of = 1 g/cm3 Stokes diameter: is the diameter of a sphere that has the same density and settling velocity as the particle.  Aerosol Work Region Size Nasopharyngeal or oropharyngeal regions, e.g., nasal spray for > 10 µm perennial rhinitis, such as corticosteroid Central airway, e.g., mucokinetic 5 to 10 µm drugs Oropharynx and large airways to the overall lower respiratory tract 2 to 5 µm (large airways to periphery), e.g., bronchoactive aerosols Terminal airways and alveolar 0.8 to 3 region, e.g., anti-infective drug µm pentamidine Know this chart http://aerosol.ees.ufl.edu/healthaerosol/section01.html for the exam  Settling Velocity Adapted from Stoke’s (describes the motion of viscous fluid substances) Dae = aerodynamic diameter, Dv = volume equivalent diameter, Pp = density of the particle Equation is more complex than this though For all spherical particles: eliminate “Slip factors”/shape factors All particles sized between 2 to 5 micron: eliminate slip factor Use slip factors for particles