PPI Suspension Stability via Poloxamer and Buffer Systems
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Solution Overview
Problem
Patients, particularly pediatric and geriatric populations, face challenges in swallowing solid dosage forms of proton pump inhibitors (PPIs), necessitating a stable and palatable liquid formulation for effective management of acid-related disorders.
Innovation Solution
A stable liquid formulation of a compounded suspension of PPIs, comprising a copolymer of ethylene oxide and propylene oxide, simethicone emulsion, a buffer system, preservative, thickening agent, sweetener, and water, which is homogenous and stable for at least 30 days at refrigerated conditions, allowing for flexible dosing and improved palatability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If solid dosage forms of PPIs are used, then stability and ease of manufacture are improved, but patient compliance deteriorates due to inability to swallow
Solution Approach 1:
The patent transforms the PPI from solid capsule form to liquid suspension form by changing the physical state parameter. This allows patients who cannot swallow solids to receive the medication in a liquid form while maintaining therapeutic efficacy through controlled pH and stability-enhancing excipients
Solution Approach 2:
The patent introduces multiple excipients as intermediaries including polymers (carboxymethylcellulose sodium, xanthan gum), buffers (sodium bicarbonate, citric acid), and stabilizers (polysorbate 80) that mediate between the PPI active ingredient and the liquid vehicle, ensuring stability, suspension, and palatability simultaneously
2Ease of operation
If liquid formulation of PPI is prepared, then patient compliance is improved, but stability and homogeneity deteriorate
Solution Approach 1:
The patent creates a composite liquid formulation system combining PPI powder with multiple functional excipients: suspending agents (carboxymethylcellulose sodium, xanthan gum), buffers (sodium bicarbonate, citric acid), stabilizers (polysorbate 80), and flavoring agents. This composite structure maintains homogeneity and stability while providing liquid form benefits
Solution Approach 2:
The patent applies different functional properties to different components of the formulation: carboxnymethylcellulose sodium and xanthan gum provide suspension and viscosity control, sodium bicarbonate and citric acid maintain pH buffer capacity, polysorbate 80 prevents aggregation, and flavoring agents improve palatability. Each component addresses specific local requirements of the formulation
3Stability of the object's composition
If multiple excipients are added to liquid PPI formulation, then stability and homogeneity are improved, but device complexity increases
Solution Approach 1:
The patent employs excipients that perform multiple functions simultaneously: carboxymethylcellulose sodium and xanthan gum serve as both suspending agents and viscosity modifiers; sodium bicarbonate and citric acid function as both pH adjusters and buffer system components; polysorbate 80 acts as both stabilizer and emulsifier. This multi-functionality reduces the need for separate additives for each function
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 liquid formulation achieves enhanced stability, improved homogeneity, and optimized viscosity, ensuring accurate and uniform dosing, increased patient compliance, and effective management of acid-related disorders in challenging patient populations.
Implementation Method 1
The liquid formulation comprises a copolymer of ethylene oxide and propylene oxide... In a particular embodiment, the copolymer of ethylene oxide and propylene oxide is Poloxamer 188
Implementation Method 2
simethicone emulsion
Implementation Method 3
a buffer system such as sodium bicarbonate and sodium citrate, as well as a preservative that is benzyl alcohol... The pH of the liquid formulation is 8.0 or greater
Implementation Method 4
a preservative that is benzyl alcohol
Implementation Method 5
a thickening agent that is xanthan gum
Implementation Method 6
propylene glycol, a dye, a flavoring agent, and water. One skilled in the art will recognize propylene glycol as an aid to properly disperse xanthan gum in the liquid formulation
Data Source
AI summary
Suspensions of pump inhibitors (PPIs) are disclosed. The suspension may include a PPI, a copolymer of ethylene oxide and propylene oxide; simethicone emulsion; Sodium Bicarbonate; and Sodium Citrate, USP (Dihydrate). The suspensions have desirable viscosities and enhanced stability.