Bimodal Release of Olanzapine from Lipid Microspheres

• Published in: Journal of pharmaceutical sciences Vol. 99; no. 10; pp. 4251 - 4260
• Main Authors: Fini, Adamo, Cavallari, Cristina, Ceschel, Giancarlo, Rabasco, Antonio M.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2010; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Antipsychotic Agents - chemistry; Benzodiazepines - chemistry; bimodal release; Biological and medical sciences; Calorimetry, Differential Scanning; Crystallization; cutina®/stearic acid carrier; Drug Carriers; General pharmacology; Lipids - chemistry; Medical sciences; Microscopy, Electron, Scanning; Microspheres; olanzapine; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; phase separation; ultrasound-assisted spray congealing; olanzapine; ultrasound-assisted spray congealing; phase separation; bimodal release; cutina®/stearic acid carrier; Dibenzodiazepine derivatives; Atypical antipsychotic; Microsphere; Olanzapine; Pharmaceutical technology; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Lipids; Serotonine receptor; cutma®/stearic acid carrier; Thienobenzodiazepine derivatives; D2 Dopamine receptor; Phase separation; Microparticle; Stearic acid; Ultrasound; Release
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22146

Olanzapine was formulated as 10% (w/w) mixture with cutina® to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray-congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion. Olanzapine is distributed into the two phases according to its partition coefficient: two phases make the system less suitable to crystallization of the drug; the loading of the drug could reach saturation with difficulty and the rate of the olanzapine release is differentiated, since the drug is released from two different carriers. Dissolution profiles suggest occurrence of a bimodal release, where each portion of the release profile is linear and the slope increases with a higher content of stearic acid in the carrier mixture, that behaves as a release promoter. Tests were also carried out with palmitic and lauric acids for comparison and also for systems in the absence of ultrasound.