FORMULATION AND EVALUATION OF CLOPIDOGREL TABLET INCORPORATING DRUG NANOPARTICLES

摘要

Objective: The present study aims to enhance the dissolution rate of a poorly water-soluble drug, clopidogrel bisulfate by the preparation of the nanoparticles. Methods: Nanoparticles of clopidogrel were produced by antisolvent-precepitation method using different stabilizers at drug :stabilizer ratio 1:2 alone and in combination and characterized for particle size, drug entrapment efficiency (DEE), dissolution testing, sc anning electron microscopy imaging (SEM) and atomic force microscopy (AFM). Lyophilized nanoparticles were compressed into tablets by direct compression method and evaluated by different methods. Compatibility studies (Fourier transform infrared spectrosco py (FTIR) and differential scanning calorimetry (DSC) ), and powder x-ray diffraction (PXRD) were also done. Results: Through this study, the particle size was ranged from 5.29 to 480 nm and %DEE was ranged from 83% to 97%. Amongst all formulations F13,stabilized with PVPK-30 and PVA, showed complete dissolution (100%) at the end of 10 minutes in both media 0.1N HCL (pH 1.2) and PBS (pH 6.8).SEM of clopidogrel nanoparticles confirmed small particle size without aggregation. Particle size of F13 obtained by AFM was 250 nm. F13a tablet characterized by short disintegration time, high hardness, low friability and produced higher dissolution rate in comparison with the marketed tablet. FTIR study revealed that there is no chemical interaction between clopidogrel and the excipients. DSC and XRD illustrated that the crystallinity of clopidogrel was lost in lyophilized powder and tablet and converted to an amorphous form. Conclusion: Antisolvent precipitation method was a promising method to produce clopidogrel nanoparticles with markedly enhanced dissolution rate.