Development of an Amorphous Nanosuspension by Sonoprecipitation-Formulation and Process Optimization using Design of Experiment methodology

Publication date: Available online 2 February 2019Source: International Journal of PharmaceuticsAuthor(s): Bhavin Y. Gajera, Dhaval A. Shah, Rutesh H. DaveAbstractA Design of Experiment (DoE) methodology was adopted to investigate and optimize process parameters and formulations variables for preparing an amorphous clotrimazole (CLT) nanosuspension by sonoprecipitation technique. The amorphous nanosuspension can provide a synergistic effect of increase in dissolution velocity and kinetic solubility which can be advantageously used to improve bioavailability of low-solubility drugs. A Box-Behnken design was utilized to study the effect of formulation parameters (drug concentration, polymer concentration, and surfactant concentration) and process parameter (antisolvent: solvent ratio) on particle size, polydispersibility index (PDI), and zeta potential of amorphous CLT nanoparticles. Soluplus® and poloxamer 407 were incorporated in the formulation for steric and electrostatic stabilization respectively. The optimized formulation predicted by the developed model was validated experimentally. Micronized amorphous suspension, micronized crystalline suspension and nanocrystalline suspension were prepared as controls. The optimized amorphous nanosuspension and controls were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) and polarized light microscopy (PLM) techniques. Additionally, in-vitro dissolution studies were performed. The drug c...

Source: International Journal of Pharmaceutics - February 3, 2019 Category: Drugs & Pharmacology Source Type: research