Loading…

Enhanced intestinal absorption of vancomycin with Labrasol and d-α-tocopheryl PEG 1000 succinate in rats

Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic used for the treatment of infections caused by methicillin-resistant staphylococci. It is water soluble, having a high molecular weight, and poorly absorbed from the gastrointestinal tract. Mixtures of VCM with Labrasol and d-α-tocopheryl p...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2003-01, Vol.250 (1), p.181-190
Main Authors: Prasad, Y.V.Rama, Puthli, S.P, Eaimtrakarn, Sudarat, Ishida, Makoto, Yoshikawa, Yukako, Shibata, Nobuhito, Takada, Kanji
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic used for the treatment of infections caused by methicillin-resistant staphylococci. It is water soluble, having a high molecular weight, and poorly absorbed from the gastrointestinal tract. Mixtures of VCM with Labrasol and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared to improve oral absorption of VCM. Administration of VCM solution to rat ileum at a dose of 20 mg/kg did not result in detectable plasma VCM concentration. Formulation containing 50% of Labrasol resulted in a Cmax value of 5.86±0.97 μg/ml and an AUC 0–6h value of 16.06±1.78 μg h/ml. Addition of TPGS to VCM solution at 12.5% concentration also increased the plasma VCM concentration with a Cmax value of 4.98±0.45 μg/ml. But the AUC 0–6h (9.87±1.90 μg h/ml) was significantly lower than that obtained with Labrasol. The addition of 5.0 and 25.0% TPGS to solutions of VCM containing 50% of Labrasol did not result in any significant increase either in Cmax or AUC 0–6h of VCM. Whereas the addition of 12.5% of TPGS has resulted in an increase in Cmax and AUC 0–6h by 2.2 and 2.4 times, respectively, suggesting that this concentration of 50% Labrasol and 12.5% TPGS (1:0.25) was optimum for improving intestinal absorption of VCM. A dose dependent decrease in the Cmax and AUC 0–6h values was observed when the dose of absorption enhancers was decreased by 50% with formulation containing Labrasol and TPGS in 1:0.25 ratio. The results of the study indicate that formulations containing Labrasol and TPGS improve intestinal absorption of hydrophilic macromolecular drug, VCM.
ISSN:0378-5173
1873-3476
DOI:10.1016/S0378-5173(02)00544-6