Enhancement of solubility and improvement of dissolution rate of atorvastatin calcium prepared as Nanosuspension

Abstract EN

Atorvastatin calcium has a problem of very slightly aqueous solubility (0.1-1 mg/ml).

Nanosuspension technique applied to improve atorvastatin calcium dissolution profile.

The aim of this study is to formulate atorvastatin calcium as a nanosuspension to enhance its dissolution.Thirty one formula were prepared to evaluate the effect of ; polymer type, polymer: drug ratio, speed of homogenization, temperature of preparation and inclusion of co-stabilizer in addition to the primary one; using solvent-anti-solvent precipitation method under high power of ultra-sonication.

In this study, five types of stabilizers (TPGS, PVP K30, HPMC E5, HPMC E15, and Tween80) were used in three different concentrations 1:1, 1:0.75 and 1:0.5 for preparing of formulations.

At the same time, Tween80 and sodium lauryl sulphate had been added as a co-stabilizer in selected formulations.

Atorvastatin calcium nanosuspension was evaluated for particle size, poly dispersity index (PDI), zeta potential, crystal form and surface morphology.

Finally, the results of particle size analysis revealed reduced nano-particulate size to 81nm for optimized formula F18 ( containing drug : polymer : co-sabilizer ratio 1:1:0.5 ) with the enhancement of in-vitro dissolution profile up to 90% compared to 44% percentage cumulative release for the reference atorvastatin calcium powder in phosphate buffer pH 6.8 media.Furthermore, saturation solubility of freeze dried Nanosuspension showed 3.3, 3.8, and 3.7 folds increments in distilled water, 0.1N HCl and phosphate buffer pH 6.8, respectively.

The freeze dried powder was formulated as hard gelatin capsules and evaluated according to the USP specifications of the drug content and disintegration time.As a conclusion; formulation of poorly water soluble atorvastatin calcium as nanosuspension significantly improved the dissolution rate of the drug and enhanced its solubility.