The Dissolution Behavior of Ibuprofen and Griseofulvin in Bicarbonate Buffer Compared to Phosphate Buffer Using Intrinsic Dissolution Rate and Biphasic Dissolution

Abstract

In the small intestine, bicarbonate is the main buffering system to adjust the pH after the gastric emptying to pH 5.5-6.8. Bicarbonate gathered some attention to be used as a dissolution media to better mimic the in-vivo environment. However, in vitro the evaporation of CO2(g) interferes with the in vivo observed neutralization process. To maintain the pH, CO2(g) must constantly added. In a previous study, they predicted based on the reaction kinetics that ibuprofen dissolution in 5 mM phosphate buffer will be equivalent to 10 mM bicarbonate buffer. However the dissolution of acidic drug will alter the pH of the phosphate media. . The aim of the study was to investigate bicarbonate buffer compared to phosphate buffer as dissolution media for ibuprofen (IBU) and griseofulvin (GRI) with and without the use of bile salts, and to developed method to test the similarity between dissolution of IBU 5 mM phosphate buffer and 10 mM bicarbonate buffer. The intrinsic dissolution rate (IDR) was used to compare between dissolution of IBU and GRI in 10mM bicarbonate buffer (BCB) and phosphate buffer (PBS) with and without bile salts at pH 6.8±0.05. The pH was mentored throughout the experiments. In case of bicarbonate, CO2(g) was applied on the surface to control the pH rather than infused to avoid foaming. For IBU dissolution in 5 mM PBS two compartment system was developed. The IDR of IBU showed significant difference between BCB and PBS without bile salts, in agreement with Krieg et al. GRI IDR showed a significant difference between PBS with bile slats and BCB with bile salts, where BCB was 83% higher than PBS. This indicate a different micelles shape had been formed in BCB resulted in enhanced solubilization. The similarity of the biphasic dissolution of IBU in PBS and BCB was rejected. Indicating the need of better surrogate buffer to BCB, especially when large volume needed. We have demonstrated the importance of using bicarbonate buffer as dissolution media for class II drugs.