Conclusions

1. SEDDS formulations are useful in enhancing the oral bioavailability of poorly soluble drugs. The highly lipophilic drug PNU-74006 (Log p = 5.8) and Drug X (Log P ~ 7) show a substantial increase in oral bioavailability by use of appropriately designed SEDDS formulations. The clinical evaluation of the a high drug load (300 mg/g) Drug X SEDDS formulations revealed significantly enhanced oral bioavailability relative to the solid dosage forms.

2. The in vitro test methods demonstrated with the Drug X SEDDS formulations are useful in guiding the development of the SEDDS formulations. The emulsification spontaneity, the resulting droplet size, and the extent of drug solubilization in the aqueous medium are key attributes that are critical in achieving optimal oral exposure. Generation of microemulsion from the 300 mg/g Drug X SEDDS formulation upon in vitro dilution is proven to be crucial in improving the oral absorption of Drug X in animals and humans. An agreement between the in vivo oral bioavailability of Drug X from the SEDDS formulation and the percentage of drug release at 60 minutes is observed.

3. The enhanced oral absorption of poorly soluble drugs with the SEDDS formulation approach is presumably due to more efficient presentation of rug to the enterocyte brush border region by:

a. Equilibration of the drug with the aqueous medium and subsequent enterocyte uptake by the aqueous diffusional pathway or, alternatively.

b. Simulating or equilibrating with the BAMM system with transfer by collisional contact with the brush border glycocalyx.

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