Optimization, in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks

Abstract

Background: In recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher's attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.

Methods: Here, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.

Results: Optimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.

Conclusion: Conclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.

Keywords: Acrylamide; Itaconic acid; Semi-IPN hydrogels; Sterculia gum; pH sensitive.

Fig. 1

Proposed structure of IA-g-poly(AM)/sterculia gum semi-IPN hydrogel

Fig. 2

Deacetylation of sterculia gum

Fig. 3

Effect of sterculia gum (a and c) and IA (b and d) on dynamic and equilibrium swelling index of semi-IPN hydrogels at pH 1.2 and 7.4

Fig. 4

Swelling behaviour of I5 at pH 1.2 and 7.4. Dry discs are shown by white arrows, and placed along with swelled semi-IPN hydrogel for comparison

Fig. 5

FTIR spectra of (a) blank (without CTZ HCL), (b) drug loaded hydrogel and (c) pure CTZ HCl

Fig. 6

SEM micrograph of (a) CTZ HCl, (b) blank hydrogel and (c) drug loaded hydrogel. Drug loaded hydrogels show fewer pores as compared to blank hydrogels as is visible in inset pictures. White arrows show micro channels

Fig. 7

DSC (i) and TGA (ii) thermograms of (a) blank, (b) drug loaded hydrogel and (c) CTZ HCl

Fig. 8

XRD diffractograms of blank hydrogel (a), drug loaded hydrogel (b) and CTZ HCl (c)

Fig. 9

Cumulative percent release of CTZ HCl loaded IA-g-poly(AM)/Sterculia gum semi-IPN hydrogels (I5). CTZ HCl was observed in pH 1.2 for 2 h and then at pH 7.4 for next 70 h

Fig. 10

Histopathological images of control and treated animals. Here, G: glomerulus, BV: blood vessels, B: bronchiole, A: alveolus, AD: alveolar duct (doted red line), CV: central vein, C: cardiac muscles, PC: parietal cells, CC: chief cells