Nanocrystal-based drug delivery system of risperidone: lyophilization and characterization

Objective: In the present work nanocrystal-based formulation of risperidone (RIS) was proposed to overcome solubility issue of RIS, while lyophilization technique was used effectively, for conversion of RIS nanosuspension to solid state.

Significance: RIS nanosuspension was developed and stabilized with a combination of polycaprolactone and Pluronic^® F-68 as stabilizers. With focus on critical parameters like nature of cryoprotectants and effect of eutectic temperature on properties of nanosuspension, the suitability of lyophilization technique in improving the physical stability of prepared nanosuspension was also evaluated. Additionally, the developed nanocrystals were also assessed for their solid states properties.

Methods: Various process parameters affecting average particle size and polydispersity index (PDI), viz. drug to surfactant ratio, solvent to anti-solvent ratio, stirring speed, type of stabilizer were optimized. Assessment of lyophilization as a suitable solidification technique (for conversion to powder form) was done with selective cryoprotectants (trehalose dihydrate and sorbitol).

Results: The formulation was found to be stable at 4?°C for 3 months with size, PDI and zeta potential of 214?±?3.4?nm, 0.120, and –10.2?±?0.90?mV, respectively. Release profile of developed nanosuspension showed cumulative % release of ～90% in initial 10?h whereas the value for the unprocessed drug was ～11% in same time frame.

Conclusions: These findings suggest that developed formulation was able to enhance water solubility of the drug effectively and can be potentially used in the management of psychotic disorders.