The use of Caco-2 line cells for predicting the xenobiotics biodavailability
Keywords:Glycyrrhiza glabra root extract, glycyram, biopharmaceutical classification system, bioavailability
The biopermeability of glycyram, a biologically active substance from Glycyrrhiza glabra root was studied in the Problem Laboratory of Morphofunctional Studies of the National University of Pharmacy. Glycyram is a triterpene glycoside with a wide range of the pharmacological activity. However, the intensity of the activity depends on many pharmacokinetic characteristics of the drug, in particular on its bioavailability. Bioavailability in pharmacology reflects the ability of a medicinal substance to be absorbed in the body. It is generally assumed that passing drugs through the intestinal epithelium (a monolayer of cells) is a major barrier to the drug in its pathway into the circulatory system. The bioavailability of the glycyram substance was determined in vitro on a Caco-2 cell model reproducing most of the properties and characteristics of differentiated intestinal epithelial cells. The biopharmaceutical classification system (BCS) for active substances has been put into practice in the pharmaceutical sector of Ukraine. According to the existing BCS, the active substances are divided into 4 classes by their solubility in different media and permeability.
Aim. To determine which class of the biopharmaceutical classification system glycyram belongs to.
Materials and methods. The procedure for determining the permeability on a Caco-2 cell culture consisted of the following steps: cell cultivation, incubation of cells on a microporous filter (preparation of the test system), determination of the test suitability of the system (measurement of transepithelial electrical resistance, method calibration), determination of the permeability of the standardized substance glycyram compared to the internal standard – propranolol, quantitative determination of the test substance permeability by the HLC method with an UV or MS detector.
Results and discussion. During the experiment using the Caco-2 monolayer the average permeability value of glyceram (7.755 ± 0.517) – E-08 cm/sec was found. These data indicate that the glycyram substance has a low permeability through the epithelial layer of the intestine (less than 50 %). Considering the results of the previous studies showing a high solubility of glycyram and its low permeability it is possible to refer glycyram to class 3 according to the biopharmaceutical classification system.
Conclusions. The results of the studies obtained substantiate the feasibility of using glycyram-based dosage forms that would avoid passing the barrier of enterocytes of the small intestine, in particular pessaries, gels or creams.
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