Gastrointestinal Dissolution and Absorption of Drugs

Gladys E. Granero, Chandrasekharan Ramachandran, and Gordon L. Amidon 

FaSSIF Fasted state simulating intestinal fluid 

Drug Bioavailability Estimation of Solubility, Permeability, Absorption and Bioavailability. Edited by Han van de Waterbeemd. Hans Lennernas and Per Artursson Copyright 2003 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30438-X 

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For drugs administered oraUy, impaired gastrointestinal (GI) absorption is an important consideration. For example, aluminum ions in certain antacids or ferrous ions in oral iron supplements form insoluble chelates of tetracycline antibiotics, thereby preventing their absorption. The antifungal ketoconazole is a weak base that is only soluble at acid pH. Drugs that inhibit gastric acidity, such as the proton pump inhibitors and histamine Hj receptor antagonists, impair the dissolution and absorption of ketoconazole. 

Not understood. One suggestion is that the tricyclic antidepressants inhibit the metabolism of the anticoagulant (seen in animals with nortriptyline or amitriptyline and warfarin, but not with desipramine and acenocoumarol ), but tricyclics are not established known inhibitors of the metabolism of any drug so this seems unlikely. Another idea is that the tricyclics slow gastrointestinal motility thereby increasing the time available for the dissolution and absorption of dicoumarol. ... 

Fig. 15.1. Factors limiting oral drug absorption. Dissolution and the aqueous drug solubility in the gastrointestinal fluids are two of the properties influencing oral drug absorption. When the drug is in solution, it can be subjected to chemical degradation and complex binding with components of the gastrointestinal fluids and/or be metabolised by...

The rate and extent of absorption of drug Y will be a function of its solubility, intestinal permeability, and stability in the gastrointestinal fluids and dissolution rate. Differences in the absorption of two phannaceutically equivalent products should then primarily be a function of their in vivo dissolution rate differences, assuming the excipients used do not alter bioavailability [38]. Therefore, the key question here is Does an in vitro dissolution test emulate in vivo drug dissolution ... 

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