Release-controlling absorption enhancement of enterally administered Ophiopogon japonicus polysaccharide by sodium caprate in rats.
The aim of this study was to improve the intestinal absorption of Ophiopogon japonicus polysaccharide (OJP) by incorporating it together with sodium caprate (SC) into erodible matrices, designed to release OJP and SC at various rates over different periods of time. OJP, a graminan type fructosan with an average molecular weight in number of 3400 Da has been demonstrated to have anti-myocardial ischemic activity. The determination of OJP blood levels was carried out by the fluorescein isothiocyanate (FITC) prelabeling method. Matrix tablets, possessing different erosion rates, were prepared by changing the amounts of sodium alginate and using the two-layer tableting technique. Formulation effectiveness was evaluated by monitoring OJP plasma levels after intra-intestinal administration of each of the tablets to anesthetized rats. The findings indicate that all the SC containing formulations can significantly improve FITC-OJP bioavailability. Compared with the formulations not containing SC, the increase varied from 5.6- to 20.8-fold for the worst and best SC containing formulations studied, respectively. Moreover, there were no statistically significant differences between the C(max) and AUC(0-4) values obtained for three optimized formulations, which synchronously or nonsynchronously released both FITC-OJP and SC within 1-2 h. Their absorption enhancement effects were 2.1- to 3.6-fold higher than those of faster and slower release formulations studied. Fast delivery of the drug and its absorption adjuvant(s) contributes to their high concentrations at the absorption sites. However, at the same time, it leads to their short residence times and fast dilution by intestinal fluids. The better the balance between the two opposite effects for drug absorption, the more effective absorption enhancement would be obtained.
Lin
Xiao
X
Department of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Xu
De-Sheng
DS
Feng
Yi
Y
Li
Song-Ming
SM
Lu
Zhi-Ling
ZL
Shen
Lan
L
D000818:Animals; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D003652:Decanoic Acids / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D031441:Ophiopogon / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D011134:Polysaccharides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013607:Tablets
D002021:Buffers; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D005079:Excipients; D019999:Pharmaceutical Solutions; D011134:Polysaccharides; D013607:Tablets; C031071:decanoic acid; D016650:Fluorescein-5-isothiocyanate