A dynamic in vitro lipolysis model: I. Controlling the rate of lipolysis by continuous addition of calcium

• Published in: European journal of pharmaceutical sciences Vol. 14; no. 2; pp. 115 - 122
• Main Authors: Zangenberg, Niels Hønberg, Müllertz, Anette, Kristensen, Henning Gjelstrup, Hovgaard, Lars
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01-09-2001; Elsevier
• Subjects: Animals; Bile Acids and Salts - pharmacokinetics; Bile Acids and Salts - pharmacology; Bile salts; Biological and medical sciences; Calcium - pharmacokinetics; Calcium - pharmacology; Dissolution; Fatty Acids - metabolism; General pharmacology; Hydrolysis - drug effects; Lipase - metabolism; Lipolysis - drug effects; Medical sciences; Models, Chemical; Pancreatic lipase; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Poorly water-soluble drug substances; Rate of lipolysis; Sodium Chloride - pharmacokinetics; Sodium Chloride - pharmacology; Soybean Oil - metabolism; Swine; Titrimetry - methods; Pancreatic lipase; Rate of lipolysis; Poorly water-soluble drug substances; Dissolution; Bile salts; Enzyme; Bile salt; Solubility; Triacylglycerol lipase; Esterases; Free fatty acid; In vitro; Modeling; Lipolysis; Carboxylic ester hydrolases; Hydrolysis; Lipophilic compound; Simulation; Hydrolases; Soybean oil; Physicochemical properties; Calcium Cations
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/S0928-0987(01)00169-5

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°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+.