amorphous solid dispersions and inhaled medicine Flashcards
requirements for oral drugs
good solubility and dissolution rates, good absorption through gut (permeability)
what does bioavailable mean
proportion of drug that enters circulation, when introduced to the body, that has an active effect
oral formulations for poorly water soluble componuds
-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)
how do amorphous solid dispersions work as a oral formulation
disrupts ordered crystalline state to form a disordered amorphous state that dissolute more rapidly
what is glass transition (Tg)
transition of an amorphous material from brittle to rubbery
-lower Tg=less stable=more likely to recrystallise
2 ways to manufacture solid dispersions
- solvent based- spray drying
-rapid solvent evaporation, needs acceptable solubility of drug in low boiling solvent - heat based- holt melt extrusion
-temperature can cause degradation, no solvent required, melting point of less than 200 needed
techniques to test formulation
- DSC (differential scanning calorimetry)- tests mp
- X ray crystallography- detects ordered molecular organisation of crystals
why use amorphous form of a drug
improves properties like bioavailability and dissolution rates
structure of lungs
trachea, bronchi, bronchioles, alveoli
SA increases —>
why deliver drugs to lungs
-local and systemic effects
-rapid action
-more comfortable for patient
-smaller doses than oral so there will be less adverse effects
what is an aerosol
suspension of liquid or solid particles in a gas
why is using an aerosol good
overcomes barriers, penetrates to airways
what makes an effective aerosol particle
-deposits in the right lung region
-right quantity
-overcomes physiological barriers and respiratory defence mechanisms
what is aerodynamic diameter
diameter of a sphere with density 1gcm^3 that has the same settling velocity in the air as the particle of interest
aerodynamic diameter equation
d(aer)= d√p/p1
what is stokes law equation
v=(1/18n)d^2pg
v=settling velocity
n=viscosity
d=particle geometric diameter (um)
p=density (gcm^3)
g=gravitational acceleration
what determines the stie of particle deposition in lungs
aerodynamic diameter and stokes law, air flow
what is respirable fraction
percentage of drug present in aerosol particles that is likely to be deposited
what can be used to determine the respirable fraction
Anderson cascade impactor or next generation impinger
name and explain 3 types of inhalers and how they are aerolised
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
what does pMDI stand for
pressurised metered dose inhaler
what does DPI stand for
dry powder inhaler
how do pMDI form aerosol
evaporation of gas at atmospheric pressure
problems with pMDI
-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
problems with DPI
-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)
solutions to DPI
-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
types of DPI
-unit dose device
-multiple unit dose device
-reservoir device
advantages and disadvantages of nebulisers
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
advantages and disadvantages of pressurised metered dose inhalers
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
advantages and disadvantages of dry powder inhalers
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
