Τομέας ΦΑΡΜΑΚΕΥΤΙΚΗΣ ΤΕΧΝΟΛΟΓΙΑΣ
Library of the School of Science

2012-11-06

2012

Πετράκης Ορέστης

Ρέππας Χρήστος Καθηγητής

in vitro εκτίμηση της ενδοαυλικής συμπεριφοράς λιπόφιλων ασθενών οξέων που χορηγούνται σε διάφορες στερεές, χημικές και φυσικές φάσεις

Greek

Today's trend in discovering APIs with poor water solubility and high
lipophilicity poses a barrier to drug development process, as far as oral
bioavailability is concerned. This obstacle is overcome via the application of
several approaches, such as the formation of salts and the formation of stable
amorphous solids.

Using two model lipophilic weak acids (Α and B), in the present thesis we
evaluated:
- the usefulness of data in biorelevant media in predicting the intralumenal
solubility of a crystalline and a stable amorphous calcium salt of weak acid A,
and of weak acid B and its sodium salt.
- the usefulness of biorelevant dissolution data in predicting differences in
oral absorption rates after administration of the crystalline and the stable
amorphous calcium salt of weak acid A.

Using blank FaSSGF-V2 or FaSSGF-V2, intragastric solubility was adequately
predicted or slightly underestimated. The identity of the specific buffer
species that are used to simulate lumenal pH affect drastically the solubility,
when the acid is ionized. FaSSIF-V2 seems to be more useful than FaSSIF, in
predicting intraintestinal solubility of APIs with weakly acidic
characteristics.

In vitro dissolution data of crystalline and amorphous calcium salt of weak
acid A tablets were in line with differences in in vivo absorption rates.

Weak acids, Precipitation, Supersaturation, Biorelevant media, Dissolution

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https://pergamos.lib.uoa.gr/uoa/dl/object/1321148