The purpose of this research was to formulate and systemically evaluate in vitro and in vivo performances of mucoadhesive
amoxicillin microspheres for the potential use in the treatment of gastric and
duodenal ulcers, which were associated with Helicobacter pylori.
Amoxicillin mucoadhesive
microspheres containing carbopol-934P as mucoadhesive
polymer and
ethyl cellulose as carrier
polymer were prepared by an
emulsion-
solvent evaporation technique. Results of preliminary trials indicate that quantity of
emulsifying agent, time for stirring,
drug-to-
polymers ratio and speed of rotation affected the characteristics of
microspheres.
Microspheres were discrete, spherical, free flowing and showed a good percentage of
drug entrapment efficiency. An in vitro mucoadhesive test showed that
amoxicillin mucoadhesive
microspheres adhered more strongly to the gastric mucous layer and could retain in the gastrointestinal tract for an extended period of time. A 3(2) full factorial design was employed to study the effect of independent variables,
drug-to-
polymer-to-
polymer ratio (amoxicillin-ethyl cellulose-carbopol-934P) (X(1)) and stirring speed (X(2)) on dependent variables, i.e. percentage mucoadhesion,
drug entrapment efficiency, particle size and t(80). The best batch exhibited a high
drug entrapment efficiency of 56%; mucoadhesion percentage after 1 h was 80% and the particle size was 109 µm. A sustained drug release was obtained for more than 12 h. The
drug-to-
polymer-to-
polymer ratio had a more significant effect on the dependent variables. 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 vivo H. pylori clearance tests were also carried out by administering
amoxicillin powder and mucoadhesive
microspheres 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 a contribution to H. pylori complete eradication.