Effect of pH on the chemical stability and oil-water partition coefficient of bisoprolol fumarate

OBJECTIVE To study the effect of pH on the chemical stability and oil-water partition coefficient(P) of bisoprolol fumarate(BF) so as to provide a theoretical basis for developing a transmucous membrane absorption liquid preparation of the drug.METHODS The concentration of BF was determined by HPLC.The degradation percentage of BF solutions at 80 ℃ and the P values of the drug in n-octanol-water/ phosphate buffers system at 25 ℃ were measured under various pHs,respectively.RESULTS In the range of the investigated pH balues,the degradation percentages of BF reduced with increase of pH values.The degradation rate tended to zero while pH was above 4.0.The P value of BF in n-octanol-water system was 0.23;When the pH values were from 2.0 to 7.0,the P values of BF in n-octanol-phosphate buffers system were all less than 1.While the pH values were more than 7.0,the P values significantly increased,respectively.CONCLUSION pH values can exert a significant effect on the chemical stability and P values of BF.Thus,it is very important to select suitable pH value for studying the transmucous membrane absorption liquid preparation of BF.