Application of Galenic Strategies for Developing Gastro-Resistant Omeprazole Formulation for Pediatrics

Abstract

Objectives: This study addresses a critical need in pediatric pharmacotherapy by focusing on the development of an enteric formulation of omeprazole for pediatric use. Omeprazole, a widely used proton pump inhibitor, is essential for treating various gastrointestinal disorders in children. The main objective is to design a compounding formula that can be prepared in hospital pharmacy services without the need for industrial equipment, which is often unavailable in these settings.

Methods: The research applied different galenic strategies to overcome the challenges of omeprazole's instability in acidic environments and its complex pharmacokinetic and physicochemical properties. The experiments were conducted sequentially, employing salting out, ionic gelation, and matrix granulation strategies. Based on the results obtained, the control conditions and parameters for the various trials were established.

Results: Among the techniques used, wet granulation proved to be the most promising, achieving a gastro-resistance level of 44%. In contrast, the ionic gelation and salting-out techniques did not yield satisfactory results.

Conclusions: The findings of this study underscore the need to adopt alternative formulation strategies to ensure the stability of omeprazole. This goal requires a multidisciplinary approach and continuous effort to design omeprazole formulations that meet quality standards and appropriate gastro-resistance requirements.

Keywords: gastro-resistance; omeprazole; pediatric pharmaceutical forms.

Figure 1

Schematic representation of the experiments conducted using the salting-out methodology. In Experiment 2, the aqueous solutions were alkalinized, in contrast to Experiment 1.

Figure 2

pH 1.2 medium. Left image: omeprazole 2 mg/mL suspension in xanthan gum at 0 min. Right image: omeprazole 2 mg/mL suspension in xanthan gum at 5 min.

Figure 3

Left image: pH 2.2 medium; omeprazole 2 mg/mL suspension in xanthan gum at 5 min. Right image: pH 4.5 medium; omeprazole 2 mg/mL suspension in xanthan gum at 5 min.

Figure 4

The three pH media after 1 h and 15 min. Left: pH 1.2 medium. Middle: pH 2.2 medium. Right: pH 4.5 medium.

Figure 5

The three pH media after 2 h. Left: pH 1.2 medium (yellow color). Middle: pH 2.2 medium (light brown color). Right: pH 4.5 medium (pink color).

Figure 6

pH 1.2 medium with omeprazole base. Left image: 10 min after adding 20 mg of omeprazole base. Right image: 2 h after adding 20 mg of omeprazole base.

Figure 7

Left image: pH 1.2 medium with placebo. No color change was observed after 2 h. Right image: pH 1.2 medium with enteric-coated omeprazole pellets. No color change was observed after 2 h.

Figure 8

Left: microspheres from Experiment 2. Middle: microspheres from Experiment 3. Right: microspheres from Experiment 3 after the drying process.

Figure 9

Left: microspheres from Experiment 2. Right: microspheres from Experiment 3 in acidic medium.

Figure 10

Left: appearance of the emulsion after 10 min of mechanical agitation with paddles. Right: appearance of the emulsion after 60 min of mechanical agitation with paddles.

Figure 11

Appearance of the microspheres after the drying process.

Figure 12

Chromatogram of omeprazole.

Figure 13

Chromatogram of omeprazole microspheres produced via ionic gelation.

Figure 14

Chromatogram of omeprazole microspheres produced via salting out.

Figure 15

Chromatogram of omeprazole microspheres produced via wet granulation.

Figure 16

Schematic representation of the results obtained, and the possible alternatives proposed for obtaining gastro-resistant microspheres of omeprazole.