Cilnidipine Nanocrystals, Formulation and Evaluation for Optimization of Solubility and Dissolution Rate

Abstract

The aim of this study is to formulate and evaluate cilnidipine nanocrystals (CLD NCs) using solvent antisolvent technology. Cilnidipine has a very low solubility (BCS Class-II drug low solubility high permeability), cilnidipine (CLD) as a fourth generation Ca+2 channel blockers and extremely low medication compliance, it has been used to treat hypertension and hypertensive associated vascular disorders, cilnidipine can be prepared as nanocrystals (NCs) using solvent-anti-solvent technique with ratio 1:10 as solvent to anti solvent volume, which can improve the solubility and bioavailability. The prepared CLD NCs were evaluated for particle size, polydispersity index (PDI), dissolution study and differential scanning calorimetry (DSC). Two different stabilizers (poloxamer 188 and Tween20) were utilized to prepare nine formulas with different drug to stabilizer ratio as (1:0.25, 1:0.5 and 1:1), F4 was the smallest mean size 152 nm,PDI (0.161)and the saturated solubility was increased about ten folds, this formula was subjected for freeze drying by adding 3 % mannitol as cryoprotectant .A complete dissolution of F4 was established in about 20 minutes which confer the DSC and PXRD results in conversion from crystalline into amorphous state .It can conclude that tween 20 was a best stabilizer to be used and solvent-anti-solvent technique was a successful method in preparation of nanocrystals of CLD.