Verapamil hydrochloride nanoparticles formulated with chitosan and sodium alginate by an ionic gelation method

摘要

Purpose: To formulate chitosan-based nanoparticles for extended release of verapamil so as to reduce its dosing frequency. Methods: Nanoparticles of chitosan and sodium alginate loaded with verapamil HCl were synthesized using the ionotropic gelation method. The formulations were optimized by cross linking of tripolyphosphate with chitosan, and CaCl 2 with sodium alginate at different concentrations. The ionic gelation method was used to produce seven different formulations. The best formulation for nanoparticles preparation involved using 0.06 % sodium alginate with 18 mM CaCl 2 and of chitosan: TPP (5:1 ratio). The compatibility of verapamil HCl with sodium alginate and chitosan was tested using FTIR. Results: Verapamil nanoparticles had a direct correlation with the polymer concentrations used. A 5:1 ratio of chitosan:TPP resulted in a particle size of 173 nm, and high drug entrapment. The size of verapamil nanoparticles prepared with sodium alginate was 186 nm (p = 0.02). Cross-linking agent played an important role in the preparation of the nanoparticles. Scanning electron micrographs showed that the nanoparticles were coalesced with one another, and had rough surfaces. Chitosan-based formulations had an entrapment efficiency in the range of 38.63 – 50.58 %, while the entrapment efficiency of sodium alginate-based formulations was 11.70 – 40.57 % (p 0.43). Conclusion: Verapamil nanoparticles have been successfully formulated by ionic gelation method using natural polymers. The nano-formulations did not exhibit polymer-drug interactions, but manifest extended drug-release profiles.