Omeprazole Pellet Coating for High Drug Loading

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Solution Overview

Problem

Current methods for producing omeprazole pellets face challenges such as low drug loading, wide granule size distribution, and high manufacturing costs due to the use of wet granulation/extrusion/spherionization processes, and issues with moisture sensitivity and agglomeration in fluid bed coating, leading to inefficient production and stability concerns.

Innovation Solution

The development of pellets with a neutral core coated by a pharmaceutically active ingredient layer comprising omeprazole and binders, with a specific weight ratio of omeprazole:binder and increased thickness of the active layer, which enhances drug loading and manufacturing efficiency without requiring new equipment, and includes an enteric coating for acid protection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If wet granulation/extrusion/spherionization processes are used to produce omeprazole pellets, then granules can be formed, but the drug loading is low, granule size distribution is wide, and manufacturing costs are high

Engineering Contradiction:
Improvedrug loadingVSAvoidgranule size distribution
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent extracts and eliminates the problematic wet granulation/extrusion/spherionization steps from the manufacturing process. Instead, it uses a direct coating approach where the active ingredient layer is applied to neutral cores, removing the intermediate granulation steps that cause wide size distribution and low drug loading.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the manufacturing parameters by specifying a weight ratio of omeprazole to binder in the active ingredient layer between 3:1 and 5:1, and the weight ratio of omeprazole to neutral core between 1:1.5 and 1:4. These parameter changes enable high drug loading while maintaining uniform pellet size.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If fluid bed coating is used to apply active ingredient layer, then coating can be applied, but moisture sensitivity and agglomeration occur leading to production inefficiency

Engineering Contradiction:
Improvecoating applicationVSAvoidmoisture sensitivity and agglomeration
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent specifies precise parameter ranges for the active ingredient layer composition (omeprazole:binder ratio of 3:1 to 5:1) and thickness (more than 50 μm), which optimize the coating process to prevent moisture sensitivity and agglomeration while maintaining manufacturing efficiency.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If enteric coating is applied to protect omeprazole from gastric acid, then stability in acid environment is improved, but release rate in small intestine must be optimized for fast absorption

Engineering Contradiction:
Improvestability in acid environmentVSAvoidrelease rate in small intestine
Core Design Contradiction:
Stability of the object's compositionVSSpeed

Solution Approach 1:

The patent applies different functional layers with distinct properties: an active ingredient layer for drug delivery and an enteric coating layer for acid protection. The enteric coating provides acid resistance in the stomach while allowing rapid release in the alkaline environment of the small intestine, achieving both stability and fast absorption.

Inventive Principle:
Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach results in higher drug loading, reduced excipient usage, increased batch size, and improved manufacturing efficiency, with enhanced stability and faster absorption of omeprazole, effectively addressing the limitations of existing technologies.

Implementation Method 1

Enteric polymers do not dissolve at low pH and by this protection of the drug is ensured. After the pH increase in small intestine the polymer dissolves and releases the drug.

Methodology Applied
Scientific EffectpH-dependent dissolution:

Implementation Method 2

The layering process usually begins with neutral spherical cores that provide the solid surface on which the active layer comprising pharmaceutically active ingredient is sprayed.

Methodology Applied
Scientific EffectFluidization: Fluidisation

Data Source

PatentEP3380084B1Omeprazole formulations
Publication Date: 2019.08.21 SANDOZ LTD
  • EP3380084B1 patent drawingFigure 1
  • EP3380084B1 patent drawingFigure 2
  • EP3380084B1 patent drawingFigure 3

AI summary

The present invention refers to pellets comprising pharmaceutically active ingredient and binder. Further, the invention refers to a process for preparing said pellets, to the use of said pellets for preparing a pharmaceutical composition, and to a dosage form comprising said pellets or pharmaceutical composition. Finally, the present invention refers to a dosage from for use in a method of treating a disease selected from the group consisting of gastro esophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome and for prevention of upper gastrointestinal bleeding in people who are at high risk.