Drug-Tea Polyphenol Interaction (III) Incompatibility between Aripiprazole Oral Solution and Green Tea.

The details of incompatibility between aripiprazole (ARIP) oral solution and green tea were examined. When the ARIP oral solution was mixed with a commercial PET bottled green tea beverage, the residual rate of ARIP in the mixed solution decreased to 15.7-17.6%. Mixing with ARIP reduced the content of gallate-type green tea polyphenols (GTPs) in the mixed solution but not the content of non-gallate-type GTPs. Furthermore, using pH 3.0 lactic acid buffer, 2.23 mM ARIP solution and 2.23 mM GTP solution were prepared, and the same volumes of ARIP solution and GTP solution were mixed. When the gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution decreased. On the other hand, when the non-gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution did not decrease. From the above results, it was found that the main reason for the incompatibility between ARIP oral solution and green tea was the formation of an insoluble substance composed of ARIP and gallate-type GTPs in green tea. Furthermore, experimental results using the continuous variation method revealed that ARIP and (-)-epigallocatechin gallate, which is the most representative gallate-type GTP, interact at a molar ratio of 3 : 2.

Incompatibility between propericiazine oral solution and tea-based drink.

Here, we studied the incompatibility between an oral solution of propericiazine (PCZ), an antipsychotic drug, and various commercially available bottled tea-based drinks. When 0.5 mL of the PCZ oral solution (10 mg/mL) was mixed with 16.5 mL of a tea-based drink (such as green tea, oolong tea, and black tea), the residual PCZ content declined to approximately 50% in some mixed solutions. After mixing with other tea-based drinks, the residual PCZ content declined to approximately 30%, while in others, it changed very little. The residual PCZ content declined immediately after mixing with tea-based drinks, but the rate remained almost unchanged for the next 24 h. Furthermore, the pH of the mixture increased to 4.5-5.1 after the oral solution of PCZ (original pH 3.8) was diluted with various tea-based drinks. Afterwards, the pH did not change for 24 h. The mixture became cloudy immediately after diluting PCZ oral solution with tea-based drinks, and the insoluble substance gradually precipitated. In order to elucidate factors responsible for the decline in the content of PCZ, a (-)-epigallocatechin gallate solution, which is a main ingredient of green tea polyphenol, was mixed with the PCZ oral solution. After mixing, the residual PCZ content declined to approximately 60-75%. On the other hand, the content of PCZ did not decline when a (-)-epigallocatechin solution was mixed with the PCZ oral solution. The results from this study demonstrated that PCZ content was reduced after dilution in tea-based drinks because of the interaction between PCZ and polyphenol with a galloyl group in tea-based drinks.

Enthalpic discrimination of R- and S-limonenes in nonpolar solvents at 298.15 K.

Enthalpies of mixing of R- and S-limonene in non-polar solvents in the entire range of mole fractions were measured at 298.15 K. The enthalpies of mixing were negative for all concentrations in dilute concentration, but increased by increasing the concentration of limonenes in solutions. Ultimately positive excess enthalpies were shown in high concentration. Enthalpies of mixing were compared with theoretical estimation by COSMO-RS.