Aceclofenac-Loaded Microspheres Prepared by Vesicular Ionotropic Gelation to Minimize Drug-induced Gastric Ulcers in Rats

Abstract

Background: Aceclofenac is a non-steroidal anti-inflammatory drug and a potent analgesic. However, its oral ingestion may cause gastrointestinal problems, including dyspepsia, abnormal pain, nausea, diarrhea, and ulcerative colitis.

Objective: This study aimed to prepare vesicular-based enteric microspheres containing aceclofenac by ionotropic gelation technique to minimize gastric irritation in rats.

Methods: The micron-size vesicles were prepared by the ionic-orifice gelation method. Three types of vesicularbased microcapsules containing aceclofenac were prepared by employing sodium alginate as the coating material in combination with Eudragit L100, Eudragit S100, and polyvinylpyrrolidone PVP K90. The drug to sodium alginate to polymer ratios were 1:0.5:0.5, 1:1:1, and 1:1.5:1.5, respectively. Gelation of sodium alginate was induced by the dropwise addition of calcium chloride solution (10 % w/v). Aceclofenac-loaded microspheres were evaluated in terms of aceclofenac content and in vitro drug release, and FTIR, DSC, and XRD were used for physicochemical evaluation of some selected formulae. The effects of microencapsulation on aceclofenac-induced ulcerative activity in male Wistar rats were also investigated.

Results: The results indicated no interaction between aceclofenac and microcapsules forming polymers. In addition, microcapsules formulations M1, M4, and M7 gave maximal protection in acidic pH and optimal release in alkaline pH. The histopathological studies revealed that the reduction of ulceration is evident from the macroscopic and microscopic studies, which showed complete protection of the tissue morphology with no ulcers, indicating the effectiveness of the microcapsules system against aceclofenac-induced gastric ulceration in rats again.

Conclusion: Ionotropic gelation seems to be a simple, efficient technique to prepare aceclofenac-loaded microspheres with a reduced risk of gastric ulceration. It is possible to overcome the problem of gastric damage while utilizing aceclofenac by avoiding the exposure of the drug to the ulcer-prone area of the gastrointestinal tract.

Keywords: Aceclofenac; enteric microspheres; in vitro release; induced gastric ulcer; ionotropic gelation; rheumatoid arthritis.