Enhancement in dissolution profile of cilnidipine by nanonization technique: Optimization by box-behnken design

Cilnidipine has limited 25-30% of bioavailability due to BCS class II category drug. The aim of present work was to improve the solubility followed by dissolution rate of cilnidipine by formulation of nanosuspension.

The nanosuspensionwas developed usingnanoprecipitation techniqueaidingultra-sonication with solvent (Dimethyl sulfoxide), antisolvent (water) and stabilizer (polyvinyl alcohol). The nano formulation was statistically optimized using Design Expert software by theBox-Behnken design. The concentration of Poly Vinyl Alcohol, Volume of Antisolvent and Stirring Time were considered as independent factors whereas Particle size and polydispersity index were considered as dependent factors.

The particle size of nanosuspension was found 178.57nm with narrow polydispersity index of 0.130. The microscopy study confirmed amorphous nature particles with rough surface. The zeta potential of 4.55 ±2.78 for optimized formulation finds stability of formulation during storage. The differential scanning calorimetry study and X-ray diffraction pattern showed the crystalline cilnidipine drug was converted to amorphous form upon precipitation into nanoparticles. Due to the nanonization of cilnidipine, the dissolution profile was noted as 92.41±3.56% which was significantly improved as compared with plain drug release data. The stability data showed satisfactory result for 2 months.

It is summarized that the nanoprecipitation technique with ultra-sonication is approaching method for the formulation of homogenous nanosuspension with uniform sized dispersion of cilnidipine. Therefore, it can be assumed that the upon the enhancement in dissolution rate, the cilnidipine loaded nanosuspension may lead to improved absorption of drug from intestine followed by significant improvement in bioavailability.