Formulation and evaluation of stomach-specific amoxicillin-loaded carbopol-934P mucoadhesive microspheres for anti-Helicobacter pyloritherapy

Abstract

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.

Formulation and evaluation of glipizide floating-bioadhesive tablets

“…Extended-release dosage forms with prolonged residence times in the stomach are highly desirable for the drugs with narrow absorption windows, stability problems in the intestinal or colonic environments, locally acting in the stomach, and poor solubility in the intestine (Streubel, Siepmann, and Bodmeier 2003). Recent approaches to increase the gastric residence time of drug delivery systems include bioadhesive devices (Alvisi et al 1996;Ponchel and Irache 1998;Patel and Chavda 2009), swelling devices that increase their size (Urquhart and Theeuwes 1984;Mamajek 1980), low density devices (Streubel et al 2003;and Raval et al 2007), floating systems (Deshpande et al 1997 andDave et al 2004), high density systems (Bechgaard and Ladefoged 1978;Davis et al 1986), magnetic systems, unfoldable and expandable systems, magnetic systems, superporous, biodegradable hydrogel systems (Singh et al 2000) and microparticulate systems (Patel and Chavda 2009). The otherwise-excellent concept of floating system suffers from a disadvantage that it is effective only when the fluid level in the stomach is sufficiently high.…”

Gastroretentive microparticles for drug delivery applications

“…The microspheres adhered to gastric mucous layer over an extended period of time and the release of drug from these microspheres was sustained for more than 12 hours. In vivo tests also showed that the microspheres exhibited better H. pylori clearance than amoxicillin administered as a dry powder (Patel and Chavda, 2008). In a similar study by Yellanki et al, amoxicillin-trihydrate microspheres were prepared using Carbopol ® 934P and ethylcellulose, the entrapment efficiency was between 78-86%.…”

“…Examples of polymers used in development of mucoadhesive microspheres include chitosan and Carbopol ® 934P, which has been used by many researchers (Chickering et al, 1995, Chun et al, 2005a because of its good mucoadhesive and biodegradable properties (Patel and Chavda, 2008).…”

“…However, the persistent rise in resistance of this bacterium to these antibiotics; the hostile environment of the stomach; reducing antibiotic bioavailability at the site of action has led to failures in treatment (Batchelor et al, 2007) and has encouraged research into producing alternatives to the commonly used formulations and gastroretentive formulations hold particular promise. Patel and Chavda (2008) developed amoxicillin microspheres with Carbopol ® 934P…”

Design Optimization and Evaluation of Gastric Floating Matrix Tablet of Glipizide

“…Approaches proposed to control the gastric residence of delivery systems in the upper gastrointestinal tract (GIT) include floating drug delivery systems (FDDS) [3][4][5], high-density [6,7], mucoadhesive [8,9], swelling and expanding [10], modified shape and other delayed gastric devices [2,11,12].…”