Ophthalmic, Otic, Nasal, Pulmonary

Question 1

What are the 3 barriers to cross in ocular admin

Drug condition
lipo/hydro
ionized/unionized

Answer 1

1. corneal
2. Blood aqueous barrier
3. Blood-retinal barrier

Lipophilic and unionized

Question 2

What is the pH of tears? what do drugs have to be to cross ?

Answer 2

7.5+

Tears = low buffer capacity
eye can tolerate pH 3.5-9 but it is important to keep drug pH similar to tears

Question 3

Disadv of topical ocular admin

Answer 3

low bioavailability (drainage in nasolacrimal duct)
absorption into conjunctiva membrane
not good for posterior segment diseases

Question 4

Define the following
Periocular admin
intraocular
Ocular iontophoresis

Answer 4

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

Question 5

What do hypotonic ocular solutions do to the eye? Hypertonic?

Answer 5

Hypotonic: swelling of eye (edema)
Hypertonic: cause shrinking of cornea (dehydration/dry eye syndrome)

Question 6

Common surfactants in ocular?
What can low surface tension solution do to eye? high?

Answer 6

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

Question 7

What can suspending and viscosity agents do to eyes? What do high viscosity do?

Answer 7

Improve cornea contact time (reduce draining rate)

High viscosity
- pain, block tear duct, blurred vision

Question 8

Disadvantages of ocular solutions

Answer 8

Fast drainage, only for aqueous soluble drugs

Question 9

When are ocular suspensions used?

Answer 9

prolonged release (slow dissolution rate)
- drugs with low water solubility
- should be less than 10 microm

Question 10

Characteristics of ocular ointments/emulsions

Answer 10

less dilution of drug with tears
- better bioavailability
- lipophilic bases
- can cause blurry vision

Question 11

Characteristic of ocular gels

Answer 11

increase contact time
- risk of blur/pain

Question 12

Characterisitic of ocular inserts

Answer 12

constant and prolonged drug release rate
- less affected by nasolacrimal drainage and tear flow

Question 13

Otic
Dosage form?
Sterile/non-sterile
pH?
Important excipient

Answer 13

• Mainly solutions
• sterile
• pH 6 (acidic)
• viscosity-modifying agents to prevent API from draining out the ear

Question 14

Requirements of nasal drugs

Answer 14

Crosses BBB, avoids first pass metabolism
- pH 5-6.5
- isotonic
- volume of 25-200 microl per nostril

Question 15

What particle size is necessary to penetrate alveoli

Answer 15

1-5microm

Question 16

What does aerodynamic diameter depend on (3)

Answer 16

particle shape, diameter, density

Question 17

How to increase effects of API (advantageous)

Answer 17

slow, steady inhalation
breath holding

Question 17

What do the follow aerodynamic diameter do?

Da 10-15um
Da 0.5-5um
da <0.5um

Answer 17

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

Question 17

Describe the metering chamber of pressurized aerosol
Upright use vs. inverted use.

Answer 17

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

Question 17

How is pressure controlled in aerosol

Answer 17

Type and amount of propellant
Nature and amount of product

Question 17

How is particle (droplet) size determined

Answer 17

Actuator nozzle

Question 18

Differentiate between the types of aerosols
Pressurized
Non-pressurized

Answer 18

1. Pressurized: metred dose inhalers (MDIs)
2. Non pressurized: dry powder inhalers, nebulizer/atomizer, soft mist inhaler
   Sprays, foams, inhalants, insufflators, etc..

Question 18

What are propellants required to have?

Answer 18

• low vapour pressure
• gas at room temp
• non-toxic
• inert

Question 18

Container requirements for aerosol
Metal
Glass

Answer 18

Withstand high pressure (7-10bar)

Metal
- aluminum, steel

Glass
- only below 25psi (1.7bar) + 50% propellant

Question 18

Which class of propellant is most commonly used in aerosol for MDIs.

Which is not used for MDIs

Answer 18

hydrofluoralkenes

NOT
- low molecule weight hydrocarbons

Question 18

Aerosol formulations
What consists of 2-phase systems

Answer 18

Solution
- drug dissolved in liquid propellant
for HFCs

Question 18

Non-pressurized aersols

Answer 18

see one note

Question 19

Emulsion systems

Answer 19

topical use
- propellant is part of internal phase

Question 19

What consists of 3 phase systems

Answer 19

Suspension
- liquid propellant + drug dissolved in water

Question 20

What is used in quality control of aerosols for aerodynamic size distribution

Answer 20

cascade impactor

Question 21

How is aerosol generated in nebulizers

Answer 21

1. passing compressed air (jet nebulizers)
2. Ultrasonic waves (ultrasonic nebulizers)
3. Passing solution through vibrating mesh (mesh nebulizers)