RELEASE OF OLANZAPINE FROM LIPID MICROSPHERES

Olanzapine, a drug for treatment of acute manic episodes, rapidly dissolves at acidic and neutral pH: to control the release, the drug was associated to lipid excipients forming a solid dispersion and formulated as 10% w/w mixture with cutina, containing stearic acid in the range 10-90% w/w of the total lipid mass. After fusion the molten mass was dropped on a ultrasound sonotrode, obtaining perfectly shaped microspheres. Thermal analysis revealed partial miscibility between the two fatty materials in the solid state with two separated melting endotherms, due to the presence of two phases, mutually saturated of the two fatty components. Olanzapine is distributed into the two phases according to its partition coefficient. This fact introduces consequences concerning the drug release: microspheres containing only cutina release 10% of the drug content: after that the release profile remains constant. On the contrary microspheres formed only by stearic acid release 100% olanzapine after 5 min. In systems containing both components, the release appears controlled and the two lipids behave oppositely, being stearic acid the promoter and cutina the retarder of the release. This way the rate and the mode of release is a function of their weight ratio inside the systems.