Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes

Abstract

The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with b-cyclodextrin (b-CD) and hydroxypropyl-b-cyclodextrin (HP-b-CD). TBM and its freeze-dried inclusion complexes were administered to rabbits (New zealand breed; n =6), in a dose of 20 mg/kg. TMB plasma levels were measured by HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum of plasma concentration (C max ) of 18.5893.27 mg/ml at 8.5 h (T max ), whereas with inclusion complexes, C max increased about two times and appeared at ca. 4 h. AUC 0-24 of complexes was about 1.6 times as much as that of the pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes was significantly greater and faster when compared with drug alone. In addition, without cyclodextrins the maximum hypoglycaemic effect (CVG max ) of TBM (34.1%) was observed at 5.6 h (Tg max ). CVG max of TBM/b-CD and TBM/HP-b-CD inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively. AAC 0-24 of inclusion complexes was 1.4 times larger than that of pure drug. Hence, the oral administration of complexed TBM not only improved the drug absorption, but also the TBM hypoglycaemic activity.

Bioavailability enhancers of herbal origin: An overview

“…An aqueous stagnant layer due its hydrophilic nature is potential barrier to the absorption of drugs [10] .…”

“…The drug molecules larger than about 0.4 nm have difficulty in passing through these aqueous channels [10] .…”

“…Particle size reduction such as micronization, nanoparticular carriers, complexation and liquid crystalline phases also maximize drug absorption [19,20] .…”

Insulin resistance and thyroid hypofunction in obese women – A cross sectional study

“…Participants underwent clinical and routine laboratory examination. From each patient five ml of blood sample was collected after an overnight fast of >8 h. Plasma glucose levels were measured using a hexokinase enzymatic reference method [11]. Fasting insulin levels were measured using a radioimmunoassay (RIA) method.…”

The Role of Physical Exercise and Diet Modification on Lipid Profile and Lipid Peroxidation in Long Term Glycemic Control Type 2 Diabetics

“…FPG was estimated by the method of Glucose Oxidase-Peroxidase (GOD-POD) by Trinder, [10] and quantified spectrophotometrically at 500 nm, Glycosylated hemoglobin was measured by BeenaRai&Pattabiramans Method [11] …”