FORMULATION, OPTIMIZATION, CHARACTERIZATION AND IN VIVO ANTI-ULCER ACTIVITY OF ESOMEPRAZOLE MAGNESIUM TRIHYDRATE GASTRORESISTANT MICROSPHERES

Krutika Sawant,Jiten Patel,Piyush Mundada,Mitali Patel

doi:10.22159/ijpps.2017v9i1.15437

Abstract

Objective: The objective of the present investigation was to prepare gastro-resistant microspheres of esomeprazole magnesium trihydrate (EMT) to prevent its degradation in the acidic environment of the stomach and enhance its bioavailability via intestinal absorption.Methods: EMT loaded gastro-resistant microspheres were prepared using hypromellose acetate succinate (HPMCAS) as the gastro-resistant polymer by ‘non-aqueous solvent evaporation’ technique. A 3-factor 3 level factorial design was used to optimise EMT: HPMCAS ratio, the concentration of Span 80 and stirring speed with respect to percent entrapment efficiency and particle size. Further characterization was carried out using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), In vitro release study and In vivo anti-ulcer activity.Results: Fourier transform infrared (FTIR) study indicated compatibility between drug and polymer. DSC study revealed that the drug was molecularly dispersed in the polymer. The optimised batch showed 49.63±1.23% drug entrapment and 170.12±3.36 μm particle size. SEM study showed that microspheres were spherical in shape. In vitro drug release study showed only 4.28±1.23% drug release in simulated gastric media in 2 hr and 93.46±1.20% release in simulated intestinal media after 1 hr from the optimised batch.Conclusion: Results of in vitro release studies indicated the gastro-resistant nature of the developed microspheres. In vivo anti-ulcer activity demonstrated that EMT loaded microspheres were able to significantly reduce ethanol-induced ulcer formation in rats’ stomach as compared to the aqueous solution of EMT. So it can be concluded that the developed gastro-resistant microspheres of EMT prevented drug release in the stomach which would lead to a significant improvement in its bioavailability through enhanced intestinal absorption

Highlights

Oral route is one of the most preferred and convenient routes for administration of the drug because of its ease of administration and production, greater flexibility in dosage form design and low cost of such a system
The bands observed in the spectrum of a mixture of esomeprazole magnesium trihydrate (EMT)+hypromellose acetate succinate (HPMCAS) did not show any shift (B) suggesting their compatibility
The bands observed in the spectrum of a mixture of EMT+HPMCP HP-55 (C) showed a shift of carboxylate peak from 1614 to 1724 cm-1 suggesting that a new chemical bond was formed, indicating an incompatibility between HPMCP HP-55 and EMT

Summary

Introduction

Oral route is one of the most preferred and convenient routes for administration of the drug because of its ease of administration and production, greater flexibility in dosage form design and low cost of such a system. A number of the controlled release systems have been developed for oral administration. The growing interest in controlled drug delivery is due to its benefits like increased patient compliance due to a reduction in unwanted side effects and dosing frequency [1, 2]. There are various approaches to target a specific site in a sustained/controlled release fashion. In comparison to single unit systems, multiple unit system has marked advantages as it spreads over a large area and avoids exposure of high concentration of drug to the mucosa. Microspheres are small spherical particles, with diameters in the micrometre range (typically 1 μm to 1000 μm). They are sometimes referred to as microparticles [4]

Methods

Results

Conclusion