Development and optimization of gastroretentive mucoadhesive microspheres of gabapentin by Box-Behnken design.

CONTEXT

Gabapentin follows saturation kinetics for absorption because of carrier-mediated transport and narrow absorption window in stomach. There is need to develop a gastroretentive formulation to maximize the absorption without crossing the saturation threshold for absorption.

OBJECTIVE

The aim was to develop a gastroretentive formulation of gabapentin to increase the fraction of drug absorbed in stomach.

MATERIALS AND METHODS

Sodium alginate and sodium carboxymethylcellulose were used to formulate the microsphere by ionotropic gelation with calcium chloride. The formulation was optimized using a three-factor, three-level Box-Behnken design.

RESULTS

The particle size varied from 559.50 to 801.10 μm, entrapment efficiency from 61.29 to 81.00% and in vitro release from 69.40 to 83.70%. The optimized formulation was found using point-prediction, and formulation OF-3 showed optimum results at 608.21 μm size, 79.65% entrapment efficiency and 82.72% drug release and 81% mucoadhesion up to 10 h. The drug release was controlled for more than 12 h.

DISCUSSION

The particle size was most influenced by sodium alginate while entrapment efficiency and drug release depended upon both polymers. The release followed Higuchi model.

CONCLUSION

Gastroretentive formulation was successfully optimized by a three-factor, three-level Box-Behnken design and found to be useful.