P3: Dry Powder Inhaler Formulations Flashcards
what are some advantages of passive DPI devices
automatically breath-actuated, relatively easy to use, patient & environmentally friendly, long term replacement of pMDIs
what is the main problem with DPIs
activated by inspiration which is highly variable
what is the mechanism of a DPI device
pt’s forced inspiratory action creates the energy required for fluidisation and entrainment of the formulation and de-aggregation of the drug for delivery to the lungs
patients need to generate a minimum inhalation flow; the energy is created by the pressure drop that results from the inhalation flow and the internal resistance of the device
what happens during fluidisation and aerosolisation of inhalation powders
static powder bed -> dilated powder bed -> aerosol generation -> dispersion of drug particles
what is the inter-relationship between the device and airflow of DPIs
internal resistance of device affects speed and acceleration of airflow through the device
acceleration of airflow affects DPI device efficacy
speed of inhalation affects how much drug is deposited in the lungs
teaching optimum technique offers real and immediate benefits for both patient and professional
device choice is critical
what are the different types of DPIs
single-unit dose (dispoable), single-unit dose (reusable), multi-unit dose, multi-dose (reservoir)
what is the delivery of respirable doses dependent on
inhalation device, patient inspiratory flow, powder formulatin
complex interaction between these factors govern the respirable dose and therapeutic efficacy
what is required for powder formulation
optomisation of flow and dispersion (aerosolisation) properties of respirable particles
physical interactions which govern these properties are dominant in respirable sized drug particles
DPI drug formulations require efficient manipulation
what factors dictate particle interactions
van der Waals forces, electrostatic forces, capillary forces
relative contribution of these components to the total adhesion/cohesion depends on the interacting materials and relative humidity
what are van der Waals forces
finite attractive force between all atoms, short range force, dominant force at low humidity, in the absence of electrostatic forces
what are capillary forces
condensation of water vapour between contagious bodies, forms a liquid bridge, magnitude of force directly related to relative humidity and hydrophobicity, usually the dominant force under ambient conditions
what are electrostatic forces
caused by frictional contact between dissimilar material; long range force; attractive or repulsive; magnitude increases at low relative humidity
what type of bonding occurs in a drug-drug interaction
cohesion
what type of bonding occurs in drug-excipient interactions
adhesion
what type of interaction occurs in drug-device interactions
segregation
what formulation strategy is used in carrier-based sysems
adhesive bond formation
inspirational force from patient
what formulation strategy is used in agglomerated systems
cohesive bond formation (inspirational force from patient)
what are the advantages of blending a drug with a carrier
allows accurate metering of small quantities of potent drug, improves handling and processing
what carrier properties influence fine particle fraction
particle size distribution, particle habit/morphology, surface morphology
when are agglomerated powder systems used
high dose drugs, where formulation using carrier-based systems is not feasible
‘free flowing’ macroscopic agglomerates can be produced via cohesive bond formation, efficient de-aggregation of agglomerates is required so that the drug is presented to the lungs as discrete particles
what are some disadvantages of DPIs
powder liberation and particle de-aggregation dependent upon pt’s ability to inhale
increased inhaled air velocity, increased de-aggregation of particles but increased potential for particle impaction
exposure to ambient conditions may decrease stability
generally less efficient at delivery than pMDI
