Olanzapine, improvement of biopharmaceutical performance in solid dosage form

Olanzapine is an effective antipsychotic drug used for the treatment of positive and negative symptoms of schizophrenia.

It suffers from poor water solubility in addition to extensive first-pass metabolism in the liver to inactive metabolites, resulting in a poor oral bioavailability of nearly 60%. The intestinal lymph vessels drain directly into the thoracic duct, after that to the systemic circulation, consequently avoiding being subjected to the portal circulation. Lipid-based formulations had been introduced in order to improve the bioavailability of orally administered drugs by targeting the lymphatic transport.

Self-nanoemulsifying drug delivery system (SNEDDS) as lipid-based formulations has recently received increasing attention in the development of oral dosage forms with the aim of improving the solubility and bioavailability of lipophilic drugs. While SNEDDS usually use high amounts of low molecular weight liquid surfactant that may cause degradation, instability of the drugs and being moreover toxic for the gastrointestinal tract.

Therefore, Pickering emulsions constitute an interesting alternative, where by the emulsion droplets are stabilised by solid particles alone or in combination with the low-molecular-weight liquid surfactants. These solid stabilised emulsions showed improved stability, especially at high internal phase ratio, when compared to the classical surfactant-based emulsions. The solid emulsifier, selected was the Cyclodextrins type which enhances the drug solubility, the drug stability and the drug loading. Download the thesis here: Olanzapine, improvement of biopharmaceutical performance in solid dosage form