The purpose of this research was to formulate and systematically evaluate in vitro and in vivo performances of mucoadhesive
amoxicillin microspheres for the potential use of treating gastric and
duodenal ulcers, which were associated with Helicobacter pylori.
Amoxicillin mucoadhesive
microspheres containing
chitosan as mucoadhesive
polymer were prepared by simple emulsification phase separation technique using
glutaraldehyde as a cross-linking agent. Results of preliminary trials indicate that volume of cross-linking agent, time for cross-linking,
polymer-to-
drug ratio, and speed of rotation affected characteristics of
microspheres.
Microspheres were discrete, spherical, free flowing and also showed high percentage
drug entrapment efficiency. In vitro mucoadhesive test showed that
amoxicillin mucoadhesive
microspheres adhered more strongly to gastric mucous layer and could retain in gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables,
polymer-to-
drug ratio (X(1)), and stirring speed (X(2)) on dependent variables i.e. percentage mucoadhesion, t(80),
drug entrapment efficiency, particle size and swelling index. The best batch exhibited a high
drug entrapment efficiency of 70 % and a swelling index of 1.39; percentage mucoadhesion after 1 h was 79 %. The drug release was also sustained for more than 12 h. The
polymer-to-
drug ratio had a more significant effect on the dependent variables. The morphological characteristics of the mucoadhesive
microspheres were studied using scanning electron microscopy. In vitro release test showed that
amoxicillin released slightly faster in pH 1.0
hydrochloric acid than in pH 7.8
phosphate buffer. In vivo H. pylori clearance tests were also carried out by administering
amoxicillin mucoadhesive
microspheres and
powder, to H. pylori infectious Wistar rats under fed conditions at single dose or multiple dose(s) in
oral administration. The results showed that
amoxicillin mucoadhesive
microspheres had a better clearance effect than
amoxicillin powder. In conclusion, the prolonged gastrointestinal residence time and enhanced
amoxicillin stability resulting from the mucoadhesive
microspheres of
amoxicillin might make contribution complete eradication of H. pylori.