Probucol Self-Emulsified Drug Delivery System: Stability Testing and Bioavailability Assessment in Human Volunteers.
BACKGROUND
Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability.


OBJECTIVE
The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers.


METHODS
The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference).


RESULTS
The results showed that formulations (F1-F4) were stable if stored at 20 °C. The mean (n=3) pharmacokinetic parameters for stable formulations were: The Cmax, 1070.76, 883.16, 2876.43, 3513.46 and 1047.37 ng/ml; the Tmax, 7.93, 7.33, 3.96, 3.67 and 4.67 hr.; the AUC (0-t), 41043.41, 37763.23, 75006.26, 46731.36 and 26966.43 ng.hr/ml for F1, F2, F3, F4 and reference, respectively. The percentage relative bioavailability was in this order: F3> F4> F1> F2>.


CONCLUSION
In conclusion, the PBSEDDS formulations were stable at room temperature. F4 showed the highest Cmax and the shortest Tmax. All the formulations showed significant enhancement of bioavailability compared with the reference. The results illustrated the potential use of SEDDS for the delivery of probucol hydrophobic compound.
['Zaghloul|Abdelazim|A|', 'Lila|Ahmed|A|', 'Abd-Allah|Fathy|F|', 'Nada|Aly|A|']
D000328:Adult D001682:Biological Availability D004339:Drug Compounding D016503:Drug Delivery Systems D004355:Drug Stability D045703:Emulsifying Agents D005260:Female D064368:Healthy Volunteers D006801:Humans D008297:Male D008875:Middle Aged D010316:Particle Size D011341:Probucol D013499:Surface Properties D055815:Young Adult
Probucol bioavailability PBSEDDS human bioavailability hydrophobic compound Self-Emulsified Drug-Delivery System (SEDDS) stability.