A simple method to improve the dissolution of repaglinide and exploration of its mechanism

In the present study,a simple and rapid method was developed to improve the in vitro dissolution of repaglinide,an oral antidiabetic drug,which was based on addition of meglumine in 50%(v/v)ethanol to dissolve repaglinide,and the drug dissolved in meglumine/50%ethanol was used directly with a binder to prepare tablets.The mechanism of solubilization of repaglinide by meglumine was studied by using infrared spectrum(IR),ultraviolet(UV)measurement through dual wavelength,differential scanning calorimetry(DSC)and X-ray powder diffraction methods.Dissolution tests of repaglinide tablets were performed in the media with different pH values and the repaglinide concentrations were analyzed by High Performance Liquid Chromatography(HPLC)method.The solubility data showed that with the meglumine concentration increasing,the solubility of repaglinide was increased.Meanwhile,tablets with the molar ratio of repaglinide and meglumine 1:2(n/n)resulted in a significant increase in dissolution compared to the repaglinide tablets without using meglumine,and nearly equal to the commercial preparations of Novo-Norm^(®),which concluded that meglumine had a great role in promoting the dissolution of repaglinide.The results of IR and UV dual wavelength methods suggested the formation of repaglinideemeglumine(REPeMEG)molecular complex.DSC results showed that the melting peak of repaglinide disappeared in the REPeMEG coprecipitate,which indicated that repaglinide was stable when existing at amorphous or molecular state.The experiment of X-ray powder diffraction showed that with the solubilization of meglumine,the crystal diffraction peak of repaglinide disappeared,which further inferred that repaglinide was formed complexes with meglumine.It was demonstrated that the method of improving repaglinide with meglumine was reliable and could be suitable for repaglinide tablets production in industry.This study also provides a feasible way to enhance the dissolution of drugs with low solubility,which will be leading to improved bioavailability of these drugs.

Enhancement of hydroxyapatite dissolution through structure modification by Krypton ion irradiation

Hydroxyapatite(HA)synthesized by a wet chemical route was subjected to heavy ion irradiation,using4 Me V Krypton ion(Kr17+)with ion fluence ranging from 1×1013 to 1×1015 ions/cm2.Glancing incidence X-ray diffraction(GIXRD)results confirmed the phase purity of irradiated HA with a moderate contraction in lattice parameters,and further indicated the irradiation-induced structural disorder,evidenced by broadening of the diffraction peaks.High-resolution transmission electron microscopy(HRTEM)observations indicated that the applied Kr irradiation induced significant damage in the hydroxyapatite lattice.Specifically,cavities were observed with their diameter and density varying with the irradiation fluences,while a radiation-induced crystalline-to-amorphous transition with increasing ion dose was identified.Raman and X-ray photoelectron spectroscopy(XPS)analysis further indicated the presence of irradiationinduced defects.Ion release from pristine and irradiated materials following immersion in Tris(p H 7.4,37?)buffer showed that dissolution in vitro was enhanced by irradiation,reaching a peak at 0.1 dpa.We examined the effects of irradiation on the early stages of the mouse osteoblast-like cells(MC3 T3-E)response.A cell counting kit-8 assay(CCK-8 test)was carried out to investigate the cytotoxicity of samples,and viable cells can be observed on the irradiated materials.