A dynamic in vitro lipolysis model. I. Controlling the rate of lipolysis by continuous addition of calcium.
Lipolysis by pancreatic lipase was investigated with the aim to establish an in vitro lipolysis model, which can be used to investigate the dissolution of poorly soluble lipophilic drug substances at controlled hydrolysis rates. The effects of three experimental parameters -- the concentrations of bile salts and Ca(2+) and the lipase activity -- were investigated. The effect on the rate of hydrolysis of emulsified soybean oil was investigated in experiments in a pH-stat at pH 6.5 and 37 degrees C. The free fatty acids produced by the hydrolysis were titrated at pH 6.5. It was shown that all three investigated parameters influence the initial rate of hydrolysis, whereas only the lipase activity and the concentration of Ca(2+) affect the subsequent stages. It was also shown that the rate of lipolysis can be controlled by the rate of adding Ca(2+). Thus, it is possible to design an in vitro model using readily available and inexpensive materials in which the hydrolysis rate can be controlled by the continuous addition of Ca(2+).
Zangenberg
N H
NH
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Müllertz
A
A
Kristensen
H G
HG
Hovgaard
L
L
D000818:Animals; D001647:Bile Acids and Salts / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics* / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008956:Models, Chemical; D012965:Sodium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology; D013024:Soybean Oil / Q000378:metabolism; D013552:Swine; D017186:Titrimetry / Q000379:methods
D001647:Bile Acids and Salts; D005227:Fatty Acids; D012965:Sodium Chloride; D013024:Soybean Oil; D008049:Lipase; D002118:Calcium