Introduction:

The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach.

Method:

Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization.

Results:

HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit's stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product.

Conclusions:

It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

        · resumen en Español     · texto en Inglés     · Inglés ( pdf )