Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Ρέππας Χρήστος, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Συμιλλίδου Μοίρα, Αναπληρώτρια Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Βερτζώνη Μαρία, Επίκουρη Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αξιολόγηση της δυνατότητας ανάπτυξης προϊόντος τροποποιημένης αποδέσμευσης του συνδυασμού δραστικών ουσιών Α και διερεύνηση της μεταβλητότητας της βακτηριακής ενεργότητας υλικού από κόπρανα ενηλίκων
Evaluation of the possibility of developing a modified release product of the combination of active substances A and investigation of the variability of the bacterial activity of fecal material from adults
Objective: The present study had 2 objectives. The first one was to evaluate the possibility of developing a modified release product containing the therapeutic combination A. The second one was to investigate the variability of bacterial activity of fecal material from adults, based on olsalazine and metronidazole degradation data.
Methods: Dissolution of immediate release product was estimated using the paddle apparatus and the mini-paddle apparatus, whereas release from three different modified release products was estimated using the flow-through apparatus. All experiments were performed in biorelevant dissolution media, in both fasted and fed state. The stability of active agents of the therapeutic combination A was assessed in SCoB (Simulated Colonic Bacteria, Vertzoni et al., 2018) from healthy adult feces. The concentration of feces in SCoB was 8.3%. The variability of bacterial activity of fecal material from healthy adults was estimated after comparing data from this study to data from a previous study and after testing whether the preservation of fecal material in -70 ◦C for 48 months significantly alters its bacterial activity.
Results: Based on in vitro data, approximately 20% of the immediate release product is expected to be dissolved in fasted stated and approximately 60% in fed state in the stomach. Regardless of the administrating conditions, release from product MR3 is expected to last longer than that from product MR1, whereas approximately 60% of the dose from product MR2 is expected to have been released by the time the formulation reaches the end of midgut. Both active substances contained in A are not subjected to bacterial degradation in SCoB. The mean halflives of metronidazole and olsalazine in fecal material from adults prepared for this stufy were 4.89 and 16.74 min, respectively. These values are similar to values derived from a previous study (6.28 and 17.49 min, respectively, Karatza et al., 2016). The effect of prererving the fecal material (-70 oC/48mo) was not found to be statistically significant for metronidazole and olsalazine.
Conclusions: Based on in vitro data, it is expected that release of A from MR3 is significantly extended and completed by the end of small intestine. Release from MR1 is completed sooner, whereas release from MR2 is completed in the large intestine, which may cause problems to absorptio taking into consideration the low permeability of therapeutic agent A1. Both therapeutic agents A1 and A2 are not expected to have clinically significant bacterial degradation problems in the lower intestine. Development of MR3 formulation is proposed in this study.
Fecal material prepared for this study does not show significantly different bacterial activity that than fecal material prepared from different volunteers, in a similar way for a previous study. In addition, preservation of fecal material in -70 οC for 48 months does not result in significant alterations in bacterial activity
Main subject category:
Other subject categories:
in vitro dissolution, biorelevant media
Number of pages:
ΔΙΠΛΩΜΑΤΙΚΗ ΓΚΟΛΦΗ ΕΥΓΕΝΙΑΣ.pdf
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