Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method

Abstract

The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.

Fig. 1

Response surface plot showing effect of factorial variables on a percent yield (acidic), b percent yield (alkaline), c percent entrapment efficiency (acidic), and d percent entrapment efficiency (alkaline)

Fig. 2

DSC thermograms of amoxicillin, amoxicillin gellan beads, and chitosan-coated amoxicillin gellan beads

Fig. 3

XRD patterns of amoxicillin, amoxicillin gellan beads, and chitosan-coated amoxicillin gellan beads

Fig. 4

FTIR spectra of amoxicillin gellan beads

Fig. 5

SEM photographs of a amoxicillin gellan bead (acidic), b amoxicillin gellan bead (alkaline), and c chitosan-coated amoxicillin gellan bead

Fig. 6

Swelling study of chitosan-coated amoxicillin gellan beads at pH 1.2

Fig. 7

Swelling study of chitosan-coated amoxicillin gellan beads at pH 7.4

Fig. 8

In vitro drug release of amoxicillin gellan beads (acidic) in 0.1 N HCl

Fig. 9

In vitro drug release of amoxicillin gellan beads (alkaline) in 0.1 N HCl

Fig. 10

In vitro drug release of chitosan-coated amoxicillin gellan beads in 0.1 N HCl

Fig. 11

In vitro evaluation of mucoadhesiveness of beads

Fig. 12

In vitro growth inhibition study