New Dosage Form of L-arginine based on its complex with cellulose acetate sulfate and activated carbon

Abstract

Introduction: The oral route of L-arginine intake, despite its great comfort, is less effective in comparison with infusions. The development of new pharmaceutical forms for oral preparation is of undoubted interest.

Objectives: To obtain a new dosage form of L-arginine by complexation with sodium salt of cellulose sulfate acetate (Na-CSA) followed by immobilization on activated carbon, and to evaluate its endothelial, cardioprotective and antihypertensive activity.

Methods: UV-, visible spectroscopy, FTIR spectroscopy, viscometry, molecular mechanics, animal experiments with male Wistar albino rats in the modeling of L-NAME-induced endothelium dysfunction.

Results: The physicochemical parameters of complexation, the adsorption activity of activated carbons of various origins with respect to individual L-arginine and its complex with Na-CSA were investigated. The greatest amount of adsorption and its smaller difference between L-arginine and the complex were taken into account when choosing activated carbon as a carrier (AUT-MI: GL-Arginine=320.2±0.1 mg/g, Gcomplex=340.2±0.1 mg/g; OU-A: GL-Arginine=210.1±0.1 mg/g, Gcomplex=235.1±0.1 mg/g; TH-90G: GL-Arginine=190.1±0.1 mg/g, Gcomplex=190.2±0.1 mg/g). Release of L-arginine as a result of its desorption into the model media of the human body was higher (96.3±0.5 wt.%) for the alkaline medium of intestines than for the acidic medium of stomach (10.0±0.1 wt.%). In animal experiments, it was shown that a combined preparation of L-arginine complex immobilized at doses of 30 mg/kg, 70 mg/kg and 200 mg/kg exhibits a pronounced antihypertensive, endothelioprotecive and cardioprotective activity at a dose of 200 mg/kg with L-NAME-induced nitric oxide deficiency (p<0.05; 30 mg/kg: EDCL-Arginine=3.6±0.3; EDCcomplex=3.0±0.2; 70 mg/kg: EDCL-Arginine=2.7±0.1; EDCcomplex=2.3±0.2; 200 mg/kg: EDCLArginine= 2.5±0.1; EDCcomplex=1.9±0.1).

Conclusion: Due to the antihypertensive, endothelial and cardioprotective activity of L-arginine as a complex with Na-CAC immobilized on activated carbon, it is possible to obtain an effective dosage form (tableted or granulated) of L-arginine for oral use.