amorphous solid dispersions and inhaled medicine

Question 1

requirements for oral drugs

Answer 1

good solubility and dissolution rates, good absorption through gut (permeability)

Question 2

what does bioavailable mean

Answer 2

proportion of drug that enters circulation, when introduced to the body, that has an active effect

Question 3

oral formulations for poorly water soluble componuds

Answer 3

-salt formation
-reduce particle size
-SEDDS (self emulsifying drug delivery system
-complexes (wrap drug in soluble structure)
-nanoparticles (increases SA:V)
-crystalline solid dispersions
-amorphous solid dispersion (disrupts crystalline structure to form disordered amorphous state, disolutes faster)

Question 4

how do amorphous solid dispersions work as a oral formulation

Answer 4

disrupts ordered crystalline state to form a disordered amorphous state that dissolute more rapidly

Question 5

what is glass transition (Tg)

Answer 5

transition of an amorphous material from brittle to rubbery

-lower Tg=less stable=more likely to recrystallise

Question 6

2 ways to manufacture solid dispersions

Answer 6

1. solvent based- spray drying
   -rapid solvent evaporation, needs acceptable solubility of drug in low boiling solvent
2. heat based- holt melt extrusion
   -temperature can cause degradation, no solvent required, melting point of less than 200 needed

Question 7

techniques to test formulation

Answer 7

1. DSC (differential scanning calorimetry)- tests mp
2. X ray crystallography- detects ordered molecular organisation of crystals

Question 8

why use amorphous form of a drug

Answer 8

improves properties like bioavailability and dissolution rates

Question 9

structure of lungs

Answer 9

trachea, bronchi, bronchioles, alveoli
SA increases —>

Question 10

why deliver drugs to lungs

Answer 10

-local and systemic effects
-rapid action
-more comfortable for patient
-smaller doses than oral so there will be less adverse effects

Question 11

what is an aerosol

Answer 11

suspension of liquid or solid particles in a gas

Question 12

why is using an aerosol good

Answer 12

overcomes barriers, penetrates to airways

Question 13

what makes an effective aerosol particle

Answer 13

-deposits in the right lung region
-right quantity
-overcomes physiological barriers and respiratory defence mechanisms

Question 14

what is aerodynamic diameter

Answer 14

diameter of a sphere with density 1gcm^3 that has the same settling velocity in the air as the particle of interest

Question 15

aerodynamic diameter equation

Answer 15

d(aer)= d√p/p1

Question 16

what is stokes law equation

Answer 16

v=(1/18n)d^2pg

v=settling velocity
n=viscosity
d=particle geometric diameter (um)
p=density (gcm^3)
g=gravitational acceleration

Question 17

what determines the stie of particle deposition in lungs

Answer 17

aerodynamic diameter and stokes law, air flow

Question 18

what is respirable fraction

Answer 18

percentage of drug present in aerosol particles that is likely to be deposited

Question 19

what can be used to determine the respirable fraction

Answer 19

Anderson cascade impactor or next generation impinger

Question 20

name and explain 3 types of inhalers and how they are aerolised

Answer 20

nebulisers-aqueous drug solution aerolised into droplets, energy provided by compressed air or ultra sound

pMDI- drug formulated into liquified gas under pressure, forms aerosol by evaporation of gas at atmospheric pressure

DPI- drug and other solid excipients in a dry powder state, no solvent, aerolisation by patient inhaling

Question 21

what does pMDI stand for

Answer 21

pressurised metered dose inhaler

Question 22

what does DPI stand for

Answer 22

dry powder inhaler

Question 23

how do pMDI form aerosol

Answer 23

evaporation of gas at atmospheric pressure

Question 24

problems with pMDI

Answer 24

-patient must coordinate inhaling and pressing
-particles leave with high velocity leading to high deposition in oro-pharynx (back of throat) and low deposition in lungs
-can be improved by using a spacer

Question 25

problems with DPI

Answer 25

-dose delivered and deposited is dependent on patients inspiratory flow which is hard to predict and replicate
-particles need to be <5um to penetrate lungs but small particles are very cohesive (will stick together)
-moisture increases agglomeration (clumping)

Question 26

solutions to DPI

Answer 26

-spherical particles to reduce contact point
-protect from moisture
-blend drug with carrier with large particle size, drug must be separated from carrier to be inhaled (mostly lactose used)
^large lactose particles deposited in the back of throat and drug deposits in lungs

Question 27

types of DPI

Answer 27

-unit dose device
-multiple unit dose device
-reservoir device

Question 28

advantages and disadvantages of nebulisers

Answer 28

advantages
-no coordination needed
-suitable for emergencies
-combination of different substances are possible
-for all age groups

disadvantages
-not portable
-pressurised gas needed
-long treatment time
-regular cleaning required
-expensive

Question 29

advantages and disadvantages of pressurised metered dose inhalers

Answer 29

advantages
-portable, compact
-dose and particle size independent of inhalation
-can be used in emergencies
-short treatment time (acts fast)
-available for most substance

disadvantages
-coordination needed
-ages 6 and up
-no control of dose
-propellent required
-high deposition in oro-pharynx

Question 30

advantages and disadvantages of dry powder inhalers

Answer 30

advantages
-small, portable
-breath actuated
-less coordination
-short treatment time
-available for most substances
-stable as there’s no solvent

disadvantages
-ages 4 and up
-not for emergencies
-sensitive to humidity
-pharyngeal deposition
-high inspiratory flow required