Isolated digesta as an effective and reliable ex vivo system to study the release profile of drug formulations : study on Candida utilis urate oxidase

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DOI:
| Published | English
Authors:
Pierzynowska, K. ; Wychowański, P. ; Mosiichuk, N. ; Shmihel, H. ; Zaworski, K. ; Lavrynenko, V. ; Donaldson, J. ; Pierzynowski, S. , et al.
Department:
Sensory Biology
Abstract:

Many artificial systems simulate the physiological state of the human gastrointestinal tract (GIT) and its separate compartments. These systems have the biorelevant media and imitate the physical forces and transit times of the GIT compartments, however, they lack the food-related and within-compartmental regulations and thus issues with translation of the data obtained to clinics arise. We aimed to introduce an alternative, simple and reliable ex vivo system which can be used in a laboratory setting, using fresh chyme from fed or fasted animals (pigs) to study the release profile of various drugs. For the present study we used porcine chyme collected from different gut compartments (stomach, duodenum and ileum) of six cross-bred male pigs in the fed state. Five different formulations of urate oxidase from Candida utilis were used as examples of tested drug substances. The performance of each formulation was tested by incubation in chyme at 37 °C for up to 4 h in the presence of uric acid. Samples were taken during the whole incubation time and the uric acid levels were estimated. The proposed ex vivo system provides information about the stability and performance of active drug substances in different gut compartments and can be used to test different formulations, assess possible drug-drug interactions, and the effects of fed and fasted conditions on the test substance of interest in the small and large intestine, taking into consideration diet-related changes in GIT secretions and intercompartmental regulation.

Keywords:
digestion model ; isolated chyme ; oral drug formulations ; urate oxidase
ISSN:
1230-1388
LUP-ID:
71b0c8f0-61c3-45aa-8ee9-16c1391c041f | Link: https://lup.lub.lu.se/record/71b0c8f0-61c3-45aa-8ee9-16c1391c041f | Statistics

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