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Low dose lipid formulations : effects on gastric emptying and biliary secretion

Kossena, Greg A and Charman, William N and Wilson, Clive and O'Mahony, Bridget and Lindsay, Blythe and Hempenstall, John M and Davison, Christopher L and Crowley, Patrick J and Porter, Christopher J. H (2007) Low dose lipid formulations : effects on gastric emptying and biliary secretion. Pharmaceutical Research, 24 (11). pp. 2084-2096. ISSN 0724-8741

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Abstract

Food stimulates changes to gastrointestinal secretion and motility patterns, however, the effect of smaller quantities of lipid, such as that contained in a lipid-based drug formulation, has not been detailed. This study aimed to examine the effects of small quantities of lipid on gastric emptying and biliary secretion. The influence of oral administration of three lipid-based formulations and a negative control formulation on gastric emptying and biliary secretion was evaluated in 16 healthy male subjects using gamma scintigraphy, ultrasonography and duodenal aspiration. Low quantities (2 g) of long chain lipid stimulated gall bladder contraction and elevated intestinal bile salt, phospholipid and cholesterol levels. Changes in gastric emptying were also evident, although these did not reach statistical significance. Administration of a similar quantity of medium chain lipid, however, had little effect on gastric emptying and gallbladder contraction and did not stimulate appreciable increases in intestinal concentrations of biliary-derived lipids. The quantities of long chain lipid that might be administered in a pharmaceutical formulation stimulate gallbladder contraction and elevate intestinal levels of bile salt and phospholipid. This effect is a likely contributor to the ability of lipid based formulations to enhance the absorption of poorly water-soluble drugs.