Τίτλος:
Estimating drug solubility in the gastrointestinal tract
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Solubilities measured in water are not always indicative of solubilities in the gastrointestinal tract. The use of aqueous solubility to predict oral drug absorption can therefore lead to very pronounced underestimates of the oral bioavailability, particularly for drugs which are poorly soluble and lipophilic. Mechanisms responsible for enhancing the luminal solubility of such drugs are discussed. Various methods for estimating intra-lumenal solubilities are presented, with emphasis on the two most widely implemented methods: determining solubility in fluids aspirated from the human gastrointestinal tract, and determining solubility in so-called biorelevant media, composed to simulate these fluids. The ability of the biorelevant media to predict solubility in human aspirates and to predict plasma profiles is illustrated with case examples. © 2007.
Συγγραφείς:
Dressman, J.B.
Vertzoni, M.
Goumas, K.
Reppas, C.
Περιοδικό:
ADVANCED DRUG DELIVERY REVIEWS
Λέξεις-κλειδιά:
Biological organs; Water, Bioavailability; Gastrointestinal tract; Oral absorption; Simulated media, Drug products, amprenavir; amprenavir phosphate; atovaquone; danazol; dipyridamole; felodipine; ibuprofen; ketoconazole, aspiration; drug absorption; drug bioavailability; drug solubility; gastrointestinal tract; human; lipophilicity; priority journal; review, Administration, Oral; Animals; Biological Availability; Computer Simulation; Fasting; Gastrointestinal Tract; Humans; Intestinal Absorption; Models, Biological; Pharmaceutical Preparations; Solubility
DOI:
10.1016/j.addr.2007.05.009
