| Amoxicillin [D-(-)-α-amino-p-hydroxybenzyl-penicillin] is an orally absorbed,semi-synthetic broad-spectrum antibiotic. It is now widely used in a standarderadication treatment of Helicobacter pylori (H. pylori) infections, often combinedwith another antibiotic and an acid-suppressing agent. After oral administration ofits conventional dosage form, amoxicillin is rapidly eliminated from stomach andabsorbed into circulation. The amoxicillin concentration in stomach is always toolow for effective eradication of H. pylori. Clinically, in such cases, the doses ofamoxicillin need to be increased, from which many side effects may result. Therefore, some researchers had prepared and reported new amoxicillinformulations, such as float tablet, mucoadhesive tablet, pH-sensitive excipientcomposition,mucoadhesive microspheres, etc., which were able to reside in thegastrointestinal tract for an extended period of time for a more effective H. pylorieradication. Among these formulations, mucoadhesive microspheres have gainedconsiderable attention due to their ability to adhere to the mucus layer, as well as torelease the drug in a sustained manner. The purpose of our study is to design a kind of mucoadhesive microspheres ofamoxicillin, using ethylcellulose (Ec) as matrix and carbopol 934P (Cb) asmucoadhesive polymer. The investigation includes: 1). formulation and preparationtechniques; 2).morphological properties; 3).drug loading and entrapment efficiency;4).in vitro drug release; 5). in vitro and in vivo evaluation of mucoadhesiveness; and6). mechanism of adhesiveness. Several kinds of adhesive polymers were studied, among which Cb was selected forpreparing the mucoadhesive microspheres of amoxicillin. With Ec (20 cps) asmatrix, Cb as adhesive polymer, amoxicillin mucoadhesive microspheres wereprepared by emulsification/evaporation techniques. The formulation and conditionsfor preparation were optimized by single-factor investigation and central composite - 3 -Abstractdesign. HPLC methods were established for amoxicillin determination. The drug loadingof three batches of microspheres prepared with optimized formulation and techniqueswere 27.73%, 26.73% and 27.21%, respectively. In vitro amoxicillin release behavior was investigated using paddle method andamoxicillin concentration determined by UV spectrophotometry. In pH 7.8phosphate buffer, amoxicillin could be sustainedly released from 30% at 2 hrs to 90%at 12 hrs. The morphological and physicochemical properties of mucoadhesive microspheresof amoxicillin were also investigated. They were lubricous, light yellow, sphericalparticles, with size ranging approximately from 500~1200 μm. Both repose and restangle of the microspheres were <30°. The moisture absortion of the microspheresreached saturation at about 2% (RH 75%, at room temperature). The residue ofpetroleum ether was <101 ppm. The amount of related substances were <1%. Theaccumulative release of amoxicillin in pH 1.0 HCl was about 90% (determinedindirectly). In vitro and in vivo evaluation of mucoadhesiveness of the microspheres werecarried out including measurement of % of microspheres remaining at the surface ofmucosa in vitro, % of microspheres remaining in the gastrointestinal tract in vivo, thedetachment force between microspheres and mucosa, etc. Compared to themicrospheres prepared without adhesive polymers, the mucoadhesive microspheres ofamoxicillin showed a stronger adhesive force with mucosa and could retain in thegastrointestinal tract for a longer period of time. The mechanisms of adhesiveness ofthe mucoadhesive microspheres were also studied using various methods, such as UVspectrophotometry, etc. After oral administration of the mucoadhesive microspheres of amoxicillin,seemingly due to the prolonged residence of microspheres in gastrointestinal tract,amoxicillin concentration in rat's stomach tissue was also higher th...
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