What is happening in GI tract? – Recent progress in formulation technologies for oral delivery of poorly soluble drugs
Kohsaku Kawakami
National Institute for Materials Science, Japan
: J Pharm Drug Deliv Res
Abstract
In addition to biological performances including efficacy and safety, drug candidates must have adequate physicochemical properties such as sufficient aqueous solubility. Physicochemical problems may be overcome by modifying chemical structure of the candidate, by employing salt or cocrystal, or by applying formulation technologies. It must be recognized that increase in solubility with aid of formulation technologies does not necessarily lead to improvement in oral absorption. Great attention has been paid to super saturatable dosage forms such as amorphous solid dispersions (ASDs) and nanocrystals, because such solids in energetically higher state frequently has an advantage in enhancing oral absorption unlike simple solubilisation technologies. When ASDs are subjected to dissolution studies, supersaturation relative to the crystalline solubility is frequently created. The true supersaturation is a state where compound is molecularly dissolved at higher concentration than its solubility. Recent observations indicate that the state created after dissolution of ASDs is not in molecularly dissolved supersaturation but includes concentrated dispersed phase, which may be transformed to solid micro/nanoparticles. This phenomenon is what we can observe in the in vitro dissolution study, and the situation in in vivo is not necessarily the same. Self-emulsifying formulations form (micro) emulsions which accommodate poorly soluble drugs in GI tract. The carrier needs to be metabolized in a wellcontrolled manner for delivering drug molecules across the membrane efficiently. Too stable or too unstable carrier does not improve the absorption. Novel knowledges for understanding absorption behaviors from super-saturatable formulation technologies will be presented with emphasis on prediction of the absorption from in vitro studies.
Biography
Kohsaku Kawakami is currently working for National Institute for Materials Science in Japan, where he is leading Medical Soft Matter Group. His interest is in basic science and development of amorphous dosage forms, and also on development of a novel drug carrier using phospholipids. He has published more than 130 papers and book chapters, and has given more than 120 invited lectures. He was working for pharmaceutical companies including Merck and Co. and Shionogi and Co. for 13 years as a Senior Scientist prior to joining the current organization, where he was taking care of physicochemical characterization, formulation studies, and DDS studies for new chemical entities. He was in University of Connecticut, School of Pharmacy from 2001 to 2002 as a Visiting Scholar. He holds a PhD in chemical engineering from Kyoto University.
