QbD BASED DEVELOPMENT, OPTIMIZATION AND EVALUATION OF CYCLODEXTRIN INCLUSION COMPLEX LOADED MATRIX TABLET FORMULATION OF FAMOTIDINE

Shabnam Ain*, Babita Kumar and Kamla Pathak

ABSTRACT

Famotidine is a potent histamine receptor (H2) blocker employed in the treatment of zollinger ellision syndrome, gastro esophageal reflux disease and peptic ulcer. It is poorly absorbed from the GI tract upon oral administration. The poor bioavailability (40-45%) with shorter biological half-life (2.5-4 hrs) of famotidine upon oral administration encourages the development of a controlled release formulation. The cyclodextrin inclusion complex loaded controlled release matrix tablets of famotidine were systematically optimized using experimental design. A central composite design was used for optimization of the two factors, concentrations of HPMCK4M and HPMCK15M, at three levels (low, medium and high). Dissolution was used as a response parameter for the prepared tablet formulations, which include Q18h (percent drug release in 18 h time period) and T90% (time required for 90% drug release). On evaluating all pre-compression parameters, it was found that the granules of formulations containing drug-β- cyclodextrin complex showed better flow ability rather than the formulations containing pure drug. Drug content for all formulations were found in the range of 95.72 to 98.78 with low standard deviation, which indicates the content uniformity of the prepared formulation batches. Formulation F7 containing 62% HPMCK15M and 38% HPMCK4M showed 88.02% release within 12 hours of dissolution study and formulation F13 containing complexed drug with same polymer blend ratio showed 98.92% release that was controlled up to 12 hours. All the formulations were stored at 40±5 ºC, 70±2%RH and subjected to stability studies upto 90 days. It showed that all the formulations are physically and chemically stable.

Keywords: Famotidine, histamine receptor blocker, bioavailability, controlled release matrix tablet, cyclodextrin.