Ophthalmic, Otic, Nasal, Pulmonary Flashcards
What are the 3 barriers to cross in ocular admin
Drug condition
lipo/hydro
ionized/unionized
- corneal
- Blood aqueous barrier
- Blood-retinal barrier
Lipophilic and unionized
What is the pH of tears? what do drugs have to be to cross ?
7.5+
Tears = low buffer capacity
eye can tolerate pH 3.5-9 but it is important to keep drug pH similar to tears
Disadv of topical ocular admin
low bioavailability (drainage in nasolacrimal duct)
absorption into conjunctiva membrane
not good for posterior segment diseases
Define the following
Periocular admin
intraocular
Ocular iontophoresis
Periocular admin
- high permeability since drug diffuse into scelara
- injection under the conjunctiva
intraocular
- injection into aqueous/vitreous humour
Ocular iontophoresis
- electric current to deliver ionized drugs
- via cornea or sclera
What do hypotonic ocular solutions do to the eye? Hypertonic?
Hypotonic: swelling of eye (edema)
Hypertonic: cause shrinking of cornea (dehydration/dry eye syndrome)
Common surfactants in ocular?
What can low surface tension solution do to eye? high?
non-ionic surfactants: polysorbate 20, polyoxyl stearate
Low:
- remove mucus layer and disrupt the tight junction, increasing drug permeation
High:
- cause foaming during productions or shaking
What can suspending and viscosity agents do to eyes? What do high viscosity do?
Improve cornea contact time (reduce draining rate)
High viscosity
- pain, block tear duct, blurred vision
Disadvantages of ocular solutions
Fast drainage, only for aqueous soluble drugs
When are ocular suspensions used?
prolonged release (slow dissolution rate)
- drugs with low water solubility
- should be less than 10 microm
Characteristics of ocular ointments/emulsions
less dilution of drug with tears
- better bioavailability
- lipophilic bases
- can cause blurry vision
Characteristic of ocular gels
increase contact time
- risk of blur/pain
Characterisitic of ocular inserts
constant and prolonged drug release rate
- less affected by nasolacrimal drainage and tear flow
Otic
Dosage form?
Sterile/non-sterile
pH?
Important excipient
- Mainly solutions
- sterile
- pH 6 (acidic)
- viscosity-modifying agents to prevent API from draining out the ear
Requirements of nasal drugs
Crosses BBB, avoids first pass metabolism
- pH 5-6.5
- isotonic
- volume of 25-200 microl per nostril
What particle size is necessary to penetrate alveoli
1-5microm
What does aerodynamic diameter depend on (3)
particle shape, diameter, density
How to increase effects of API (advantageous)
slow, steady inhalation
breath holding
What do the follow aerodynamic diameter do?
Da 10-15um
Da 0.5-5um
da <0.5um
Da 10-15um
- inertial impaction
- eliminated at oropharynx (throat)
Da 0.5-5um
- gravitational sedimentation
- settle on airway surfaces
da <0.5um
- brownian diffusion
- mostly exhaled
Describe the metering chamber of pressurized aerosol
Upright use vs. inverted use.
Upright: has dip tube (feed tube)
Inverted: no dip tube
10-15% ACTUAL delivered to airways
10% lost to adapter surface
80% in throat (oropharynx) or swalloed
How is pressure controlled in aerosol
Type and amount of propellant
Nature and amount of product
How is particle (droplet) size determined
Actuator nozzle
Differentiate between the types of aerosols
Pressurized
Non-pressurized
- Pressurized: metred dose inhalers (MDIs)
- Non pressurized: dry powder inhalers, nebulizer/atomizer, soft mist inhaler
Sprays, foams, inhalants, insufflators, etc..
What are propellants required to have?
- low vapour pressure
- gas at room temp
- non-toxic
- inert
Container requirements for aerosol
Metal
Glass
Withstand high pressure (7-10bar)
Metal
- aluminum, steel
Glass
- only below 25psi (1.7bar) + 50% propellant
Which class of propellant is most commonly used in aerosol for MDIs.
Which is not used for MDIs
hydrofluoralkenes
NOT
- low molecule weight hydrocarbons
Aerosol formulations
What consists of 2-phase systems
Solution
- drug dissolved in liquid propellant
for HFCs
Non-pressurized aersols
see one note
Emulsion systems
topical use
- propellant is part of internal phase
What consists of 3 phase systems
Suspension
- liquid propellant + drug dissolved in water
What is used in quality control of aerosols for aerodynamic size distribution
cascade impactor
How is aerosol generated in nebulizers
- passing compressed air (jet nebulizers)
- Ultrasonic waves (ultrasonic nebulizers)
- Passing solution through vibrating mesh (mesh nebulizers)
