Esomeprazole Pellets with Carrageenan and pH-Dependent Coating
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Solution Overview
Problem
Esomeprazole, a proton pump inhibitor, is unstable in humid environments and acidic conditions, posing challenges for its stability and release in oral pharmaceutical formulations, particularly in achieving rapid and stable release in the stomach acid environment.
Innovation Solution
A solid oral dosage form comprising esomeprazole and carrageenan, with optional excipients like mannitol and microcrystalline cellulose, coated with a polymer that dissolves at a pH of 5 or higher, facilitating rapid and stable release of the active ingredient.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If esomeprazole is formulated in conventional oral dosage forms to protect from acid degradation, then chemical stability is improved, but release speed deteriorates (slow release)
Solution Approach 1:
The dosage form is divided into multiple pellets (10-1000 pellets per tablet) with specific size ranges (0.3-2.0mm diameter). This segmentation allows the coating to provide acid protection while the small size and high surface area-to-volume ratio enable rapid disintegration and release, resolving the contradiction between stability and release speed
Solution Approach 2:
Different regions of the dosage form have different properties: the polymer coating provides acid stability and controls release, while the inner pellet core contains the active ingredient for rapid release. The coating thickness and composition are locally optimized to achieve both protection and rapid release upon contact with neutral pH environments
2Speed
If esomeprazole is formulated as amorphous solid or syrup, then rapid release is improved, but chemical stability deteriorates
Solution Approach 1:
The pellets are pre-coated with acid-stable polymer material before final assembly into tablets. This preliminary coating action provides immediate acid protection to the rapidly releasing inner core, preventing degradation while maintaining fast release characteristics
Solution Approach 2:
The dosage form combines amorphous esomeprazole (for rapid release) with crystalline excipients and polymer coatings (for stability). This composite structure integrates the advantages of different material states: the amorphous core provides rapid dissolution while the crystalline coating and matrix provide structural stability and acid protection
3Stability of the object's composition
If alkaline salts of esomeprazole are used to increase stability, then chemical stability is improved, but dosage precision deteriorates
Solution Approach 1:
The active ingredient esomeprazole is extracted from its alkaline salt form and incorporated into protected pellets with precise coating. This allows the use of stable alkaline salts during manufacturing while achieving precise dosage delivery through the controlled release mechanism of the coated pellet system
Solution Approach 2:
The formulation changes the physical state and form of esomeprazole from bulk alkaline salt to finely dispersed coated pellets. This parameter change enables precise dosage control through the uniform size distribution (0.3-2.0mm) and controlled release properties of the coated pellets, while maintaining the chemical stability benefits of the alkaline salt form
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
The formulation ensures rapid and even release of esomeprazole, achieving both physical and chemical stability, with carrageenan acting as a disintegrant and binder, and the polymer coating ensuring stability and controlled release in the acidic stomach environment.
Implementation Method 1
Carrageenan is a polysaccharide with high absorbing capacity for water
Implementation Method 2
Carrageenan is a polysaccharide with high absorbing capacity for water
Implementation Method 3
coated with a polymer dissolving only at a pH value of 5 or higher
Implementation Method 4
pass the acid environment of the stomach without damage
Data Source
AI summary
The invention relates to solid oral pharmaceutical compositions in the form of pellets, mini- tablets, tablets, or capsules, comprising an optionally substituted 2-(pyridylmethylsulfinyl)-1H- benzimidazole, for example esomeprazole, and carrageenan, and optionally one or more excipients. Surprisingly, it has been found that these compositions are stable and rapidly release the active ingredient. The pellets or mini-tablets may be coated as such, or filled in capsules or pressed into tablets, with a polymer, which dissolves only at a pH value of 5 or higher, optionally over a stabilizing intermediate layer.