in gelatin capsule

Aqueous suspension

S-SEDDS softgel

Cmax (ng/mL)

621 (45)

804 (45)

2061 (34)

Tmax (hr)

2.15 (42)

0.97 (43)

1.03 (36)

AUC [(ng/mL)ahr]

5060 (45)

4892 (45)

7004 (41)

Abbreviation: S-SEDDS, supersaturatable self-emulsifying drug delivery systems.

Abbreviation: S-SEDDS, supersaturatable self-emulsifying drug delivery systems.

HPMC was encapsulated in softgels and these softgels were orally administered to fasted humans (23 subjects, cross-over).

The plasma concentration versus time profiles for Drug X administered as each of these formulations are shown in Figure 10 and the mean C , T„ , and

AUC values are reported in Table 5. The conventional powder formulation in the gelatin capsule showed the lowest Cmax (621 ng/mL) and the aqueous suspension showed a slightly higher Cmax (804ng/mL). In contrast, the S-SEDDS softgel showed the highest Cmax (2061 ng/mL) and this is an impressive 300% increase in the Cmax and a 40% increase in the AUC as compared with that of the powder formulation. The highest Cmax and the largest AUC along with the shortest Tmax (~1 hour) were observed with the S-SEDDS softgel containing suspended HPMC indicating rapid and more complete absorption. It is interesting to note that in the dog, the same S-SEDDS formulation performed similar to the aqueous suspension (Fig. 8B) whereas in the human the S-SEDDS formulation of Drug X was clearly superior with respect to Cmax and AUC (Fig. 10).

The remarkable improvement in the oral bioavailability of Drug X in the S-SEDDS formulation containing HPMC in the clinical study is attributed to the generation and the maintenance of a supersaturated state in the GI tract. A proposed mechanism for enhanced oral absorption of poorly soluble drugs in S-SEDDS formulations is described next.

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