P3: Dry Powder Inhaler Formulations

Question 1

what are some advantages of passive DPI devices

Answer 1

automatically breath-actuated, relatively easy to use, patient & environmentally friendly, long term replacement of pMDIs

Question 2

what is the main problem with DPIs

Answer 2

activated by inspiration which is highly variable

Question 3

what is the mechanism of a DPI device

Answer 3

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

Question 4

what happens during fluidisation and aerosolisation of inhalation powders

Answer 4

static powder bed -> dilated powder bed -> aerosol generation -> dispersion of drug particles

Question 5

what is the inter-relationship between the device and airflow of DPIs

Answer 5

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

Question 6

what are the different types of DPIs

Answer 6

single-unit dose (dispoable), single-unit dose (reusable), multi-unit dose, multi-dose (reservoir)

Question 7

what is the delivery of respirable doses dependent on

Answer 7

inhalation device, patient inspiratory flow, powder formulatin
complex interaction between these factors govern the respirable dose and therapeutic efficacy

Question 8

what is required for powder formulation

Answer 8

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

Question 9

what factors dictate particle interactions

Answer 9

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

Question 10

what are van der Waals forces

Answer 10

finite attractive force between all atoms, short range force, dominant force at low humidity, in the absence of electrostatic forces

Question 11

what are capillary forces

Answer 11

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

Question 12

what are electrostatic forces

Answer 12

caused by frictional contact between dissimilar material; long range force; attractive or repulsive; magnitude increases at low relative humidity

Question 13

what type of bonding occurs in a drug-drug interaction

Answer 13

cohesion

Question 14

what type of bonding occurs in drug-excipient interactions

Answer 14

adhesion

Question 15

what type of interaction occurs in drug-device interactions

Answer 15

segregation

Question 16

what formulation strategy is used in carrier-based sysems

Answer 16

adhesive bond formation

inspirational force from patient

Question 17

what formulation strategy is used in agglomerated systems

Answer 17

cohesive bond formation (inspirational force from patient)

Question 18

what are the advantages of blending a drug with a carrier

Answer 18

allows accurate metering of small quantities of potent drug, improves handling and processing

Question 19

what carrier properties influence fine particle fraction

Answer 19

particle size distribution, particle habit/morphology, surface morphology

Question 20

when are agglomerated powder systems used

Answer 20

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

Question 21

what are some disadvantages of DPIs

Answer 21

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