Dissolution of solid lipid extrudates in biorelevant media

• Published in: International journal of pharmaceutics 2012-01, Vol.422 (1), p.116-124
• Main Authors: Witzleb, R., Müllertz, A., Kanikanti, V.-R., Hamann, H.-J., Kleinebudde, P.
• Format: Article
• Language: English
• Subjects: Anthelmintics - chemistry; Bile Acids and Salts - chemistry; bile salts; Biorelevant medium; Chemistry, Pharmaceutical; digestion; Dissolution; Drug Storage; drugs; extrusion; Glycerides - chemistry; Humidity; hydrochloric acid; Hydrochloric Acid - chemistry; Hydrogen-Ion Concentration; In vitro lipolysis; Intestinal Secretions - chemistry; Kinetics; Lipase - chemistry; Lipids - chemistry; Lipolysis; Palmitates - chemistry; Pancreatic lipase; Paraffin - chemistry; phospholipids; Phospholipids - chemistry; polysorbates; Polysorbates - chemistry; Praziquantel; Praziquantel - chemistry; Solid lipid extrudates; Solubility; solubilization; Surface Properties; surfactants; Technology, Pharmaceutical - methods; Temperature; Time Factors; triacylglycerol lipase; Triglycerides - chemistry; tripalmitin
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.10.037

Solid lipid extrudates with the model drug praziquantel were produced with chemically diverse lipids and investigated regarding their dissolution behaviour in different media. The lipids used in this study were glyceryl tripalmitate, glyceryl dibehenate, glyceryl monostearate, cetyl palmitate and solid paraffin. Thermoanalytical and dissolution behaviour was investigated directly after extrusion and after 3 and 6 months open storage at 40 °C/75% RH. Dissolution studies were conducted in hydrochloric acid (HCl) pH 1.2 with different levels of polysorbate 20 and with a biorelevant medium containing pancreatic lipase, bile salts and phospholipids. Furthermore, the impact of lipid digestion on drug release was studied using in vitro lipolysis. The release of praziquantel from cetyl palmitate and glyceryl monostearate in the biorelevant medium was much faster than in HCl, whereas there was hardly any difference for the other lipids. It was shown that drug release from glyceryl monostearate matrices is driven by both solubilisation and enzymatic degradation of the lipid, whereas dissolution from cetyl palmitate extrudates is dependent only on solubilisation by surfactants in the medium. Moreover, storage influenced the appearance of the extrudate surface and the dissolution rate for all lipids except solid paraffin.