Unit:
Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Author:
Kostaridis Alexandros
Supervisors info:
Χρήστος Ρέππας, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ,
Μαρία Βερτζώνη, Αναπληρώτρια Καθηγήτρια, Τμήμα Φαρμακευτικής, ΕΚΠΑ,
Γεωργία Βαλσαμή, Καθηγήτρια, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Original Title:
Evaluating the impact of gastrointestinal transfer on early exposure of Compound B using the BioGIT system: free base vs di-HCl salt
Translated title:
Evaluating the impact of gastrointestinal transfer on early exposure of Compound B using the BioGIT system: free base vs di-HCl salt
Summary:
Aims: (1) Evaluation of differences in intraluminal behavior between the free base and a new batch of the di-hydrochloride salt of Compound B using the BioGIT system. (2) Evaluation of the reproducibility of BioGIT data when using the di-hydrochloride salt.
Methods: The BioGIT system was used for (1) investigation of two doses of Compound B-free base, 400 mg and 800 mg granules without lubricant for suspension, (2) investigation of Hard Gelatin Capsules containing 800 mg of Compound B-diHCl and evaluation vs. the BioGIT data of the 800 mg of Compound B-free base granules, (3) comparing BioGIT data of Hard Gelatin Capsules containing 600 mg of Compound B-diHCl from a previous study with BioGIT data of Compound B-diHCl of a new batch of di-HCl salt at the same dose collected from the present study, (4) comparing BioGIT data from Hard Gelatin Capsules containing 600 mg of di-hydrochloride salt of Compound B with BioGIT data of 600 mg of di-hydrochloride salt without using capsules.
Results: (1) In the duodenal compartment, when using the free base at the 800 mg dose level, concentrations were slightly more supersaturated than at the 400 mg dose level. (2) At the 800 mg dose level, supersaturation was maintained for longer period when using the free base. (3) At the 600 mg dose level, the new batch of the salt exhibited faster precipitation than the previous batch. (4) At the 600 mg dose level, the salt precipitates faster when capsules are not used.
Conclusions: (1) Increasing the dose level of Compound B-free base led to higher concentrations in the duodenal compartment of BioGIT due to higher incoming concentrations from the gastric compartment. (2) Supersaturation is maintained for shorter period when using the salt due to smaller particle size and higher solubility in the gastric compartment of BioGIT, leading to higher concentrations and faster precipitation in the duodenal compartment. (3) In the previous batch of the salt, partial disproportionation to the free base could have contributed to variable and/or decreased tendency to precipitation. (4) When di-HCl is used without the capsules, supersaturation and precipitation occurs earlier in the duodenal compartment of BioGIT, as the absence of capsule shell leads to faster dissolution of the shell in the gastric compartment, hence, to increased incoming concentrations in the duodenal compartment.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
gastrointestinal drug absorption, in vitro evaluation, weak bases, BioGIT system
File:
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ΠΕΡΓΑΜΟΣ.pdf
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File access is restricted until 2027-05-21.
