Real-time dissolution behavior of furosemide in biorelevant media as determined by UV imaging

Abstract

The potential of UV imaging as a new small scale flow-through dissolution testing platform and its ability to incorporate biorelevant media was tested. Furosemide was utilized as a model poorly soluble drug, and dissolution media simulating conditions in the small intestine (5/1.25 mM and 40/10 mM bile salt/phospholipid, pH 6.5) together with corresponding blank buffer were employed. Dissolution rates as a function of flow rate (0.2–1.0 mL/min) were determined directly from UV images, and by analysis of collected effluent using UV spectrophotometry. A good agreement in dissolution rates was observed, however repeatability of data based on measurement of collected effluent was superior to that obtained by UV imaging in the utilized prototypic flow cell. Both methods indicated that biorelevant media did not markedly increase the dissolution rate of furosemide as compared to buffer. Qualitatively, UV images indicated that uncontrolled swelling/precipitation of furosemide on the compact surface was occurring in some samples. In situ Raman spectroscopy together with X-ray diffraction analysis confirmed that the observations were not due to a solid form transformation of furosemide. The presented results highlight the complementary features of the utilized techniques and, in particular, the detailed information related to dissolution behavior which can be achieved by UV imaging.

Keywords::

• Flow through Raman spectroscopy
• UV/Vis spectroscopy
• biorelevant dissolution testing
• simulated intestinal media

Acknowledgment

The work presented in this paper is the result of a collaborative project, carried out in partnership between the University of Copenhagen, the Institute of Pharmaceutical Technology, Goethe University, Frankfurt and the US Food and Drug Administration (FDA).

Declaration of interest

This research project was in part financially supported by the FDA Center for Drug Evaluation and Research Critical Path Funding Program. The views expressed in this article are those of the authors and do not necessarily reflect the opinions of their companies/institutions or the official policy of the FDA. No official endorsement by the FDA is intended or should be inferred. The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.