Formulation and in vivo study of the solid effervescent system as a new strategy for oral glutamine delivery

Abstract

Glutamine (GLN) used as a dietary supplement is practically insoluble in water, which reduces its bioavailability after oral administration. Here, effervescent GLN (EBGLN) was prepared by comminution with an effervescent base (EB) that enhances its water solubility. EB (80 mg/mL) composed of citric acid, tartaric acid, and sodium bicarbonate was used in the ratio 1:2:3. This formulation was characterized in the liquid state (solubility studies, pH, effervescence time, GLN content) and solid-state (size analysis, residual moisture, flow properties studies, differential scanning calorimetry, thermogravimetric analysis, powder x-ray diffraction, and Fourier transformed infrared Raman spectroscopy). In vivo studies were performed with adult overnight fasted (15 h) rats. The rats were euthanized 30, 60, and 120 min after the oral administration (gavage) of water (vehicle of GLN), EB (vehicle of EBGLN), GLN (glutamine dissolved in water), or EBGLN (GLN dissolved in EB). Blood was collected and the plasma concentrations (nmol/mL) of GLN, glutamic acid, alanine, aspartic acid, asparagine, histidine, serine, arginine, tyrosine, tryptophan, methionine, phenylalanine, valine, leucine, and isoleucine were obtained by high-performance liquid chromatography (HPLC) analysis. Physicochemical characterizations indicated that EBGLN was present as a physical mixture with lower crystallinity and higher solubility when compared with pure GLN. In vivo experiments demonstrated improved oral GLN bioavailability from EBGLN (500 mg/kg - 30 min and 60 min). Therefore, the solid effervescent system represents a new strategy for oral glutamine delivery with potential clinical relevance.