Formulation, Design and In-Vitro Characterization of Clopidogrel Bisulphate Nanosponge Tablets for Oral Administration

Abstract

Poor bioavailability by the oral route is noticeable with the majority of new active pharmaceutical ingredients due to its dissolution rate limited absorption. A second-generation thienopyridine antiplatelet drug, though, it is BCS class II drug results in poor oral bioavailability. The present investigation was undertaken to prepare polymeric nanosponges to achieve improved solubility of clopidogrel bisulphate. Nanosponges using ethyl cellulose as a polymer and glutarldehyde as a cross-linker were prepared successfully by emulsion solvent diffusion method. Drug polymer compatibility study were performed by FTIR and DSC. To obtain optimized batch, 32 factorial designs were performed and all batches were evaluated. C1-C9 batches yields particle size (nm) between 87.28-183(nm), % drug content between 71.073±1.066 -88.663 ±0.549, % entrapment efficiency between 51.719±0.775- 81.765±0.506, % drug release 75.120±0.407-97.416±0.336. Optimized batch exhibited particle size 87.28nm, % drug content 88.663 ±0.549, % entrapment efficiency 81.765±0.506, % drug release 97.416±0.336. An SEM and TEM image of optimized batch shows spongy and spherical nature of nanosponges. The optimized nanosponge formulations were converted into tablets to achieve immediate release drug delivery for oral route. These tablets were prepared using crospovidone and pregelatinised starch. All nine tablet batches were evaluated and F3 batch shows good results i.e. hardness (kg/cm2) 3.71±0.04, in- vitro disintegration time (min) 3.21±0.025 and % drug release 99.18±1.38. In vitro dissolution studies indicate that percent cumulative drug release follows zero order kinetics. Accelerated and long term stability data revealed no significant change in drug content and drug release at the end of 6 months. In conclusion, nanosponges could be a newly emerging approach to enhance aqueous solubility of BCS Class II drugs.