Inclusion complex of methyl-β-cyclodextrin and olanzapine as potential drug delivery system for schizophrenia

• Published in: Carbohydrate polymers 2012-08, Vol.89 (4), p.1095-1100
• Main Authors: Freitas, Márcia Rocha de, Rolim, Larissa Araújo, Soares, Monica Felts de La Roca, Rolim-Neto, Pedro José, Albuquerque, Miracy Muniz de, Soares-Sobrinho, José Lamartine
• Format: Article
• Language: English
• Subjects: absorption; Antipsychotic Agents - chemistry; antipsychotics; Applied sciences; Benzodiazepines - chemistry; beta-Cyclodextrins - chemistry; bioavailability; Biological and medical sciences; Cyclodextrin; cyclodextrins; Dissolution rate; Drug Carriers - chemistry; Drug delivery; drug delivery systems; Exact sciences and technology; General pharmacology; Humans; Medical sciences; Natural polymers; Olanzapine; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; schizophrenia; Schizophrenia - drug therapy; Solubility; Stability; Starch and polysaccharides; stoichiometry
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2012.03.072

► Olanzapine, a high cost drug, is the most important antipsychotic drug on the market. ► Olanzapine has low aqueous solubility, affecting its dissolution and absorption. ► Methyl-β-cyclodextrin was the most effective alternative to olanzapine drug delivery. ► The product developed has higher stability and dissolution rate than the drug alone. Olanzapine (OLP), the most important atypical antipsychotic drug of the new generation, a high cost drug, has low aqueous solubility, affecting its dissolution and absorption. Its complexation with modified cyclodextrins (CDs) is designed to achieve novel vectorization systems with higher solubility, consequently higher bioavailability. From the CD selection, among β-CD, methyl-β-CD (MβCD) and hydroxypropyl-β-CD, it was obtained a phase solubility diagram suggesting a 1:1 (mol:mol) OLP–CD stoichiometry and complexation constants of 966.9, 149.4 and 91.1L/mol, respectively. The MβCD was selected for the inclusion complexes (IC) attainment, a physical mixture (PM) and a rotatory evaporator product (ROE). The analysis showed differences in the structure, morphology and performance of OLP, MβCD, PM and ROE, revealing the occurrence of interactions between drug and CD. The ROE presented the higher dissolution efficiency and stability. The results suggest that the IC was formation, being a technological resource efficient and profitable for drug delivery.