Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability.
The capability of transglycosylated materials, α-glycosyltransferase-treated stevia (Stevia-G) and α-glycosyl hesperidin (Hsp-G), to enhance the bioavailability of poorly water-soluble drugs was investigated. Spray-dried particles (SDPs) of drug/transglycosylated material, such as, flurbiprofen (FP)/Stevia-G, probucol (PRO)/Stevia-G, FP/Hsp-G, and PRO/Hsp-G were prepared. All SDPs showed pronounced improvement in both dissolution rate and apparent drug solubility. The amount of dissolved PRO was significantly improved to that of untreated PRO crystals when prepared as SDPs of PRO/Stevia-G or PRO/Hsp-G. There was no cytotoxicity to Caco-2 cells at levels of 10% Stevia-G or Hsp-G solution. Values for the area under the plasma concentration-time curve (AUC) of untreated PRO, SDPs of PRO/Hsp-G and PRO/Stevia-G after oral administration to rats were 4.94±2.06, 26.08±4.52 and 48.79±9.97μgh/mL, respectively. Interestingly, AUC values in cases of the FP system were in the order of untreated FP<SDPs of FP/Stevia-G<SDPs of FP/Hsp-G. The effect on drug absorption enhancement may depend on the type of transglycosylated materials used. Stevia-G, a newly investigated material for this purpose, was found to have good potential for use as a pharmaceutical excipient.
Uchiyama
Hiromasa
H
Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
Tozuka
Yuichi
Y
Imono
Masaaki
M
Takeuchi
Hirofumi
H
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D005079:Excipients / Q000737:chemistry* / Q000633:toxicity; D005480:Flurbiprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006031:Glycosylation; D006569:Hesperidin / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000737:chemistry* / Q000633:toxicity; D011341:Probucol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D036625:Stevia / Q000737:chemistry*; D018675:Toxicity Tests
D005079:Excipients; D010936:Plant Extracts; D005480:Flurbiprofen; D006569:Hesperidin; D011341:Probucol