Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 50, Issue -, Pages S127-S147Publisher
ELSEVIER
DOI: 10.1016/S0169-409X(01)00182-X
Keywords
lipid digestion; dissolution; absorption prediction; lipophilic drug; formulation; lipid
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In recent years there has been an increase in interest in the utility of lipid based delivery systems, at least in part as a result of the effective development of lipid based products such as Sandimmun Neoral (R) M (cyclosporin), Norvir (R) (ritonavir) and Fortovase (R) (saquinavir). The development pathway for lipid based formulations, however, is still largely empirical, and in vitro models that are predictive of oral bioavailability enhancement are lacking. The use of modified dissolution media, reflecting the bile salt and phospholipid levels in the intestine, has met with some success in terms of the ability to predict the bioavailability of poorly water soluble drugs and the potential bioavailability enhancing effects of food. These approaches, however, do not have the flexibility or complexity to deal with the interactions inherent in the digestion, dispersion and solubilisation of a lipid based formulation and the coincident dissolution profile of a co-administered drug. In this review, the utility of modified dissolution media to predict the impact of food on the absorption of poorly water soluble, lipophilic drugs, is explored. These dissolution based systems are subsequently contrasted with the use of lipid digestion models which have found increasing application in assessment of the interaction of digestible dose forms with the gastrointestinal milieu. (C) 2001 Elsevier Science BM All rights reserved.
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