DEVELOPMENT AND OPTIMIZATION OF GASTRORETENTIVE MUCOADHESIVE MICROSPHERES USING 33 FACTORIAL DESIGN

This experimental work aimed at formulating and systemically characterizing mucoadhesive amoxicillin microspheres for the eradication of H.pylori and its associated diseases. The  microsphere batches were prepared by emulsion-solvent evaporation technique with the use of carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier polymer. Initially 27 formulations were prepared using 33 factorial design using Design Expert software. Results of preliminary trials showed that amount of drug-to-polymers ratio, emulsifying agent and stirring speed influenced the characteristics of microspheres. Prepared microspheres were discrete, spherical, free flowing with good percentage of drug entrapment. An in-vitro mucoadhesive test showed that amoxicillin microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 33factorial design was employed to study the effect of independent variables, drug-to-polymer-to-polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X1), Emulsifying agent (X2) and stirring speed (X3) on dependent variables, drug entrapment (Y1), particle size (Y2). The best batch exhibited a high drug entrapment efficiency of 66% and In vitro mucoadhesion after 1 h was 79%. A sustained drug release was obtained for more than 12 h. The morphological characteristics of the mucoadhesive microspheres were studied under a scanning electron microscope. In vitro release test showed that amoxicillin released slightly faster in pH 1.2 hydrochloric acid than in pH 7.8 phosphate buffer. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make a contribution to H. pylori complete eradication.