Influence of lipolysis and droplet size on tocotrienol absorption from self-emulsifying formulations.
A single dose comparative bioavailability study was conducted to evaluate the bioavailability of tocotrienols from two self-emulsifying formulations, one of which produced an emulsion that readily lipolysed under in vitro condition (SES-A), while the other produced a finer dispersion with negligible lipolysis (SES-B) in comparison with that of a non-self-emulsifying formulation in soya oil. The study was conducted according to a three-way crossover design using six healthy human volunteers. Statistically significant differences were observed between the logarithmic transformed peak plasma concentration (Cmax) and total area under the plasma concentration-time curve (AUC(0-infinity)) values of both SES-A and -B compared to NSES-C indicating that SES-A and -B achieved a higher extent of absorption compared to NSES-C. Moreover, the 90% confidence interval of the AUC(0-infinity) values of both SES-A and -B over those of NSES-C were between 2-3 suggesting an increase in bioavailability of about two-three times compared to NSES-C. Both SES-A and -B also achieved a faster onset of absorption. However, both SES-A and -B had comparable bioavailability, despite the fact that SES-B was able to form emulsions with smaller droplet size. Thus, it appeared that both droplet sizes as well as the rate and extent of lipolysis of the emulsion products formed were important for enhancing the bioavailability of the tocotrienols from the self-emulsifying systems.
Yap
Siew Ping
SP
School of Pharmaceutical Sciences, University of Science Malaysia, 11800 Minden, Penang.
Yuen
Kah Hay
KH
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002839:Chromans / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005989:Glycerides; D006207:Half-Life; D006801:Humans; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009930:Organic Chemicals; D010316:Particle Size; D011136:Polysorbates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013024:Soybean Oil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D024508:Tocotrienols / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000097:blood
D002839:Chromans; D004655:Emulsions; D005989:Glycerides; D009930:Organic Chemicals; D011136:Polysorbates; D024508:Tocotrienols; C440220:Labrasol; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8; D013024:Soybean Oil; C082032:tocotrienol, alpha