Influence of food: The food effect challenge caused by poor dissolution in the absence of food.

Poorly water-soluble lipophilic drugs can demonstrate highly variable bioavailability when taken with or without food. In the fasted state, poorly water-soluble lipophilic drugs generally have poor bioavailability attributed to slow dissolution kinetics. In contrast, when taken concomitantly with food, the drug readily dissolves in the fat content of food; bioavailability is thereby no longer limited by dissolution kinetics. This food-related dissolution can lead to variability in toxicity and efficacy.

NanoCrystal® Technology can reduce the food effect of poorly water-soluble drugs. NanoCrystal® particles in contrast, to micron-sized particles, do not exhibit dissolution rate-limited bioavailability in the fasted state. The plasma profile tends to be comparable to that of the fed state thus decreasing fed/fasted variability. In a clinical trial comparing dry filled capsules of Nanoformulation™ of danazol and commercial micronized danazol, the NanoCrystal® formulation demonstrated far less variation between fed and fasted absorption. Similarly a reduced variation was seen in a NanoCrystal® formulation for a client's New Chemical Entity (NCE).

The NanoCrystal® Formulation of Emend® illustrates reduction in fed/fasted variability in humans.

Fed Fasted Ratio Emend (Clinical Data)
Source: Merck