pH值依赖的利培酮化学稳定性、溶解度及油水分配系数研究

Effect of pH on the chemical stability, solubility and oil-water partition coefficient of risperidone

目的研究pH值对利培酮(RIS)的化学稳定性、溶解度及油水分配系数(P)的影响,为研制RIS的黏膜给药制剂奠定基础。方法采用HPLC法测定RIS的浓度;在不同pH值下,分别测定RIS在80℃条件下的降解百分率,在25℃条件下的溶解度以及在37℃正辛醇-水/缓冲液系统中的P值。结果在pH<10.0时,随着pH值的增大,RIS的降解百分率逐渐增加,溶解度明显降低;当pH≥8.0时,RIS几乎不溶;RIS在正辛醇-水系统中的P值为1.46。在正辛醇-缓冲液系统中,当pH<5.0时,RIS的P值远<1;当pH>5.0时,随着pH值增加,药物的P值显著增加。结论pH值对RIS的化学稳定性、溶解度以及P值均有明显影响。选择适宜的pH值对研制RIS的黏膜给药制剂非常重要。

Objective To determine the effect of pH on the chemical stability, solubility and oil-water partition coefficient （P） of risperidone （RIS） to provide a theoretical basis to develop a transmucous membrane absorption preparation of the drug. Methods The concentration of RIS was determined by HPLC. The degradation percentage of RIS aqueous solution at 80 ℃, the solubility of RIS at 25 ℃ and the P value of the drug in noctanol-water/phosphate buffers system at 37 ℃ were measured under various pH values, respectively. Results When the pH was below 10, the degradation percentage of RIS increased with the pH values. The solubility of RIS obviously reduced with the increase of pH values. When the pH values were equal to or above 8.0, RIS was almost insoluble; The P value of RIS in noctanol-water system was 1.46; When pH values were under 5.0, the P value of RIS in noctanol-phosphate buffer system was less than 1, when the pH value was above 5.0, the P value of RIS were markedly increased with the increase of pH. Conclusion pH value has a significant effect on the stability, solubility and P value of RIS. It is important to choose a suitable pH value to study the transmucous membrane absorption of the drug.