Enhancing the aqueous solubility and dissolution of olanzapine using freeze-drying

Abstract

The aim of the present study was to develop an olanzapine freeze-dried tablet (FDT). The solubility and dissolution rate of poorly water-soluble olanzapine was improved by preparing a freeze-dried tablet of olanzapine using the freeze-drying technique . The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was poured in to the pockets of blister packs and then was subjected to freezing and lyophilisation. The FDT was characterised by DSC, XRD and SEM and was evaluated for saturation solubility and dissolution. The samples were stored in a stability chamber to investigate their physical stability. Results obtained by DSC and X-ray were analysed and showed the crystalline state of olanzapine in FDT transformation to the amorphous state during the formation of FDT. Scanning electron microscope (SEM) results suggest reduction in olanzapine particle size. The solubility of olanzapine from the FDT was observed to be nearly four and a half times greater than the pure drug. Results obtained from dissolution studies showed that olanzapine FDT significantly improved the dissolution rate of the drug compared with the physical mixture (PM) and the pure drug. More than 90% of olanzapine in FDT dissolved within 5 minutes, compared to only 19.78% of olanzapine pure drug dissolved over the course of 60 minutes. In a stability test, the release profile of the FDT was unchanged, as compared to the freshly prepared FDT after 90 days of storing.Uniterms: Freeze-dried tablets/development. Olanzapine/freeze-dried tablets. Olanzapine/solubility. Olanzapine/stability. Olanzapine/dissolution. Freeze-drying. O objetivo do presente estudo foi desenvolver comprimidos liofilizados de olanzapina (FDT).A solubilidade e a taxa de dissolução da olanzapina, fracamente solúvel em água, foram melhoradas com a preparação de comprimidos liofilizados de olanzapina usando a técnica de liofilização. O FDT foi preparado por dispersão do fármaco em solução aquosa de materiais altamente solúveis em água, como gelatina, glicina e sorbitol. A mistura foi colocada em blisters e, então, submetida ao congelamento e liofilização. O FDT foi caracterizado por DSC, Difração de Raios X e microscopia eletrônica de varredura(SEM) e avaliaram-se a solubilidade de saturação e a dissolução. As amostras for5am armazenadas em câmara de estabilidade para investigar a estabilidade física. Os resultados obtidos com DSC e Raios X foram analisados e mostraram a transformação do estado cristalino da olanzepina em FDT no estado amorfo durante a formação do FDT. Os resultados da SEM sugerem a redução do tamanho das partículas de olanzapina. A solubilidade da olanzapina do FDT melhorou significativamente a taxa de dissolução do fármaco comparativamente à mistura física (PM) e ao fármaco puro. Mais do que 90% da olanzepina no FDT dissolveu em 5 minutos, comparativamente aos 19,78% do fármaco puro dissolvido em 60 minutos. No teste de estabilidade, o perfil de liberação d...

Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties

“…Olanzapine is a second-generation atypical neuroleptic drug approved by the Food and Drug Administration as a first-line therapy for the treatment of schizophrenia and mania associated with bipolar disorder (Abdelbary and Tadros, 2013). It suffers from poor aqueous solubility (12-44 µg mL -1 ) and a low dissolution rate leading to an erratic bioavailability (Kulkarni et al, 2010;Dixit et al, 2011;Raman et al, 2013). Moreover, the drug undergoes extensive hepatic first-pass metabolism and is required in high doses (Sood et al, 2013).…”

“…Several approaches have been reported to enhance the solubility and dissolution rate of olanzapine, e.g. solid-dispersions (Krishnamoorthy et al, 2011), nano-emulsions (Raman et al, 2013), solid-lipid nanoparticles (Sood et al, 2013), freeze dried tablets (Dixit et al, 2011) and inclusion complexation with cyclodextrins (Kulkarni et al, 2010;de Freitas et al, 2012).…”

Mefenamic acid taste-masked oral disintegrating tablets with enhanced solubility via molecular interaction produced by hot melt extrusion technology

“…Mefenamic acid (MA) [2-(2,3-dimethyl phenyl) aminobenzoic acid], is a non-steroidal anti-inflammatory agent, which acts by inhibiting the activity of cyclo-oxygenase-2 and thereby the production of prostaglandin [21]. It is an odorless white or light gray powder with a melting point of 230°–231°C, with an unpleasant taste, which could lead to patient compliance issues [22, 23] was used as a model drug.…”

Design of Olanzapine/Lutrol Solid Dispersions of Improved Stability and Performances

“…The drug was also associated with hydrophilic polymers with the aim of improving the dissolution parameters in different formulations, such as freeze-dried tablets with micronized gelatine [4], controlled release tablets in the presence of methocel and ethocel [5], long acting microspheres formed by different polylactic/polyglycolic acid (PLGA) co-polymers [6], or in the form of inclusion complexes with cyclodextrins [7,8]. …”