1. ASD tends to normalize early drug substance discovery lots and in vivo studies|
a. Greater than 50% early discovery lots are amorphous
b. Residual solvent levels are actually lower with ASD than other solid forms
c. More consistent formulatability for discovery dosing
d. More soluble form for use in combination with other solubilized systems
e. Minimize pH and food effect variability preclinically (from single to multidose)
f. Physical stability in dosing suspension is good surrogate for crystallization propensity
2. Provides relatively physiologically benign vehicle for drug delivery
a. Pre-GLP high dose toxicokinetic studies and multiday toxicology studies
b. GLP toxicology studies
3. Provides a relatively benign vehicle for drug delivery in GI disease models
a. Infectious bowel disease (Crohn’s disease, colitis)
b. Potential for minimally upsetting enteric flora?
1. Known Knowns|
a. Preclinical to clinical to commercial product transition less well understood
b. Lacking surrogate assays with reliable translation
2. Known Unknowns
a. Selecting for a molecule which subsequently requires ASD for delivery
i. Risk of failure due to crystallization on storage
ii. Limited room for dose escalation due to limited drug loading
b. Less ability to mitigate chemical liability
c. More resource intensive at both GLP and GMP stages than conventional products
i. Longer timelines for progression?
ii. Greater cost of goods?
3. Unknown Unknowns
a. Potential for unexpected ADME and toxicology properties
i. Unexpected distribution and clearance?
ii. In vivo crystallization? (locally/systemically)