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 NovoNorm®, 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 repaglinide–meglumine (REP–MEG) molecular complex. DSC results showed that the melting peak of repaglinide disappeared in the REP–MEG 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

An Investigation of the Differences between the North American Dipole and North Atlantic Oscillation

This study examines the differences between the North American dipole (NAD) and the North American Oscillation (NAO) in terms of their spatial structure, temporal variations, and climate impacts. The results indicate that the sea level pressure anomalies associated with the NAD are located in more western and southern areas than those associated with the NAO, and that the NAD has its own temporal variability. In addition, the NAD has a greater influence on sea surface temperature (SST) and precipitation anomalies in the northern tropical Atlantic (NTA) than the NAO does in the North Atlantic. In the tropical Pacific, the NAD tends to be more effective in forcing SST warming during spring in the northeastern subtropical Pacific (NESP). This can extend equatorward to reach the equatorial central Pacific in the autumn, finally leading to a central Pacific (CP)-type El Niño event. In contrast, the NAO induces only weak SST warming over the NESP, so that a CP-type El Niño event does not occur. Additional analysis indicates that the influence of the NAO can pass to the tropical Pacific only when the NAD and NAO have the same sign, suggesting that the NAD may serve as an important bridge linking the NAO to El Niño⁻Southern Oscillation (ENSO)