Table 1.

Strategies for the formulation of poorly absorbed drugs.

Technology	Potential advantage	Potential disadvantage	References
Conventional micronization	Known technology, freedom to operate, solid dosage form possible	Poor control of the size distribution of the particles, insufficient improvement in dissolution rate	[24]
Nanocrystals obtained by ball-milling	Established products in the market, experienced technology, solid dosage form possible	Available only under license, secondary process required to avoid aggregation of nanocrystals	[7, 8]
Nanocrystals obtained by dense gas technology	Alternative nanocrystal processing method, still room to develop new IP	Unproven technology, secondary process required to avoid aggregation of nanocrystals	[8]
‘‘Solid solutions”—drug immobilized in polymer	Freedom to operate, new extrusion technology offers solvent-free continuous process, fast and continuous process, low cost	Physical stability of product questionable, possibility of crystallization of drug or polymer	[25]
Self-dispersing ‘‘solid solutions” with surfactants	Steric hindrance to aggregation built into product, amenable to extrusion	Physical stability of product questionable, drug may crystallize	[10, 25, 26]
Nanoparticles and solid lipid nanoparticles	Controlled-release of drug, reduced variability	Low drug loading, drug expulsion after polymorphic transition, high water content	[27]
Lipid solutions (LFCS Type I lipid systems)	GRAS status, simple, safe, and effective for lipophilic actives; drug is presented in solution avoiding the dissolution step, excellent capsule compatibility	Poor solvent capacity, limited to highly lipophilic or very potentdrugs, requires encapsulation	[6, 19]
Self-emulsifying drug delivery systems (SEDDS) and SMEDDS (LCFS Type II or Type III lipid systems)	Prior art available, dispersion leads to rapid absorption and reduced variability, absorption not dependent on digestion	Surfactant may be poorly tolerated in chronic use, soft gel or hard gel capsule can be used but seal must be effective, possible loss of solvent capacity on dispersion (Type III)	[6]
Solid or semisolid SEDDS	Could be prepared as a free flowing powder, filled in capsules or compressed into tablet form, reduced problem of capsule leakage	Surfactant may be poorly tolerated in chronic use, physical stability of product questionable, drug or polymer may crystallize	[25, 28]
Surfactant-cosolvent systems (LFCS Type IV ‘‘lipid” systems)	Relatively high solvent capacity for many drugs (due to surfactant), disperses to micellar solution, reduced variability and irritancy (due to dispersion of surfactant by cosolvent)	Surfactant may be poorly tolerated in chronic use, loss of solvent capacity on dispersion, significant threat of drug precipitation on dilution	[6, 29]