Verification of the EDA Concept Through an Assessment of Theoretical Failure Modes, Failure Mode Analysis, and Case Studies with Real Data - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 256

Bulk density
Uniform PSD
Shape of particles

Geometry/Dimensions

Thermodynamic state (crystalline,
amophous content)

Device

Surface roughness/Smoothness

Content uniformity/Potency/API
concentration
Aggregation

Spread of PSD API
pre-micronized
Spread of PSD API
post-micronized
Age micronized material or excipients

Type (e.g. pure jet-milled; blend)
Stickiness/Humidity of components

Adhesion forces (API-API; API-excipients)

Fluidization, flow ability

Dispensing methods

API purity

Powder weight/Volume/Distribution within dosage unit

API polymorphic form

Formulation

Container interaction

API static charge
API and or excipients amorphous content
API and or excipients surface properties
API physical properties
Spread PSD
excipients
Quality/Consistency/Variability

Segregation

Physical properties

APSD Change Batch size

Product
(Formulation/Device/Packaging)

Compaction

Chemical stability

Environmental conditions

Environmental conditions Holding time

Raw
material

Holding time
Packaging
Scale

Packaging

Storage Scale

Storage Headspace

Headspace
Handling
lntermediate container

Handling

Intermediate container

API water content

API residual solvent
API and or excipients
physical properties

Denaturation (biologicals)
Morphology (biologicals)
Primary, secondary, tertiary structure (biologicals)
surface protein (excipients)

Fig. 9.6 Potential causes for APSD changes related to a DPI ( From [ 9 ] —used with permission )