Title : ?rabinogalactan and Glycyrrhizic acid as promising agents for oral drug delivery
Abstract:
Oral drug delivery is the most popular route because of the low expenses and long-term compliance. However, this introduction route has several limitations for drug molecules. Some of them are low water solubility and poor bioavailability. To overcome these limitations “host-guest” inclusion complexes of drugs with natural polysaccharide arabinogalactan (AG) and saponin glycyrrhizic acid (GA) can be applied. Arabinogalactan is a polysaccharide found in the wood cell walls of higher plants. Most of the commercially available AG is obtained from woody tissue of larches, in Russia it is Larix sibirica and gmelinii. Its LD50 > 5 g/kg and its usage approved by FDA and Russian pharmacopeia. GA is the chief sweet-tasting constituent of Glycyrrhiza glabra. It is used worldwide as a food sweetener and as part of licorice preparations, as a medicinal product.
All studied inclusion complexes were synthesized mechanochemically and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. For all of them primary pharmacological properties were evaluated in vivo. For the several complexes pharmacokinetic parameters after oral introduction were obtained (Cmax, Tmax, AUC, T12, MRT) and Caco-2 permeability experiments were carried out.
We have studied AG and/or GA inclusion complexes with following drugs: NSAIDs aspirin, ibuprofen, naproxen; antihypertensive drug nifedipine; broad-spectrum antihelminthic agents albendazole and praziquantel; cholesterol lowering drugs simvastatin and atorvastatin. In all cases it was found that such complexation results in significant drug’s bioavailability enhancement and effective dose reduction.
Thus, inclusion complexes with AG and GA are a simple and effective way to enchase oral bioavailability of different drugs.
