Aqueous Solubility Enhancement of Mirtazapine: Effect of Cosolvent and Surfactant

Abstract

The poor aqueous solubility of drugs is a challenging problem faced by pharmaceutical scientists in drug formulation. Cosolvency and micellization techniques have been severally used to enhance the solubility of poorly aqueous soluble drugs. Mirtazapine, a tetracyclic antidepressant used for the treatment of moderate to severe depression and anxiety, has very poor aqueous solubility. The objective of the study was to investigate the effect of solubilizing agents (cosolvents and surfactants) on the aqueous solubility of mirtazapine while envisaging that any significant improvement in its aqueous solubility could contribute towards alleviating the withdrawal symptoms often associated with the drug. The solubility of mirtazapine was determined at room temperature in aqueous mixtures of cosolvents (propylene glycol and polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80 and sodium lauryl sulfate). An exponential increase in mirtazapine solubility was observed when total drug solubility in water-cosolvent system was plotted against cosolvent fraction volume. Polyethylene glycol 400 gave larger solubilization capacity (σ) when compared to propylene glycol. With the surfactants, linear relationship between the total solubility of the drug in water-surfactant mixtures and surfactant concentration was noted. Sodium lauryl sulfate showed the largest solubilization power (k) when compared to the nonionic surfactants (polysorbate 20 and polysorbate 80 respectively). A linear relationship between standard free energy and partition coefficient was also observed. The result of the study shows that aqueous solubility of mirtazapine is significantly improved by cosolvency and micellization and therefore there exists the possibility of improving the withdrawal symptoms often experienced with the drug. It also suggests that large free energy is required for drugs with high partition coefficients to permeate the biological membrane.

Enhanced stability of phenylethyl resorcinol in elastic vesicular formulations

“…There were no significant differences in the solubility of PR in various pH condition and ethanol concentrations between 48 and 72 h, displayed no noticeable differences, which indicated that the solubility of PR had reached equilibrium. The low water solubility of PR may be due to the inability of water, to break into the lattice structure of PR [19]. On the other hand, when the co-solvent systems were used, the PR solubility increased when the ethanol concentration increased.…”

Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: in-vitro characterization and in-vivo assessment

“…The samples were agitated for 48 hours at 37 ± 1 °C in an incubator shaker. The solution was passed through a 0.45 μm Millipore filter, and the drug concentration was evaluated by UV- Vis spectrophotometer at λ max 293 nm (K. E. Ezealisiji et al., 2015 ).…”

“…Additionally, it has a low bioavailability of about 50%. It was estimated that increasing its water solubility might result in increased bioavailability and reduce the dose required to achieve the desired therapeutic effect (K. E. Ezealisiji et al., 2015 ).…”

Fabrication of Hydroxypropyl Methylcellulose Orodispersible Film Loaded Mirtazapine Using a Syringe Extrusion 3D Printer

“…This indicates a high hydrophobicity, but it does dissolve in ethanol and an acidic condition. The MTZ has a low bioavailability (50%), high protein-binding (85%), and a long half-life (20-40 h) [4]. MTZ has a relatively narrow therapeutic index and should be individually optimized to obtain a therapeutic effect [5].…”