Hydroxycarbamide Oral Solution Stability via pH and Xanthan Gum
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Solution Overview
Problem
Existing oral solutions of hydroxycarbamide suffer from instability and short shelf-life, particularly when stored at higher temperatures, leading to the formation of unknown degradation impurities.
Innovation Solution
An oral pharmaceutical solution comprising hydroxycarbamide with a pharmaceutically acceptable aqueous carrier, including a buffer and xanthan gum, is formulated to maintain a pH between 3.0 and 6.0, significantly enhancing the stability and shelf-life of the solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If hydroxycarbamide is formulated in an aqueous oral solution with pH adjusted to 6.5-6.7, then the solution maintains stability at refrigeration temperatures, but the solution forms unknown degradation impurities when stored at higher temperatures and has limited shelf-life
Solution Approach 1:
The patent applies parameter changes by adjusting the pH of the aqueous solution to a lower range of 5.0-6.0 and optimizing the concentration of xanthan gum to 0.5-2.4 mg/ml. This modification of chemical parameters prevents the formation of degradation impurities while maintaining solution stability, resolving the contradiction between stability and impurity formation.
Solution Approach 2:
Xanthan gum is introduced as an intermediary stabilizing agent in the solution. It acts as a protective mediator that prevents degradation of hydroxycarbamide by maintaining the structural integrity of the solution and preventing molecular interactions that lead to impurity formation, thereby eliminating the harmful degradation effect.
2Stability of the object's composition
If hydroxycarbamide oral solution is stored at refrigeration temperatures (2°C to 8°C), then the solution remains stable, but the solution requires continuous refrigeration and cannot be stored at higher temperatures
Solution Approach 1:
The patent changes the chemical parameters of the solution by adjusting pH to 5.0-6.0 and optimizing xanthan gum concentration, which fundamentally alters the stability profile of hydroxycarbamide. This enables the solution to maintain stability across a broader temperature range including room temperature, thereby increasing storage adaptability without sacrificing stability.
Solution Approach 2:
The invention replaces the requirement for continuous refrigeration (an expensive and logistically complex storage condition) with a chemically stabilized formulation that can be stored at ambient temperatures. This makes the product more accessible and easier to distribute, especially in resource-limited settings.
3Reliability
If the pH of the hydroxycarbamide solution is adjusted to 6.6, then the solution appears stable initially, but the amount of unknown impurity increases significantly with time especially when stored at 25°C/60% RH
Solution Approach 1:
The patent identifies that pH 6.6, while providing initial stability, leads to progressive degradation over time. By changing the pH parameter to the optimized range of 5.0-6.0 and combining it with optimized xanthan gum concentration, the formulation achieves both initial stability and long-term durability, extending the shelf-life significantly.
Solution Approach 2:
The invention incorporates stability feedback by monitoring the behavior of hydroxycarbamide at different pH levels and storage conditions. This feedback information is used to optimize the formulation parameters, ensuring that the solution maintains its stability profile throughout the intended shelf-life under various storage conditions.
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 solution exhibits excellent physicochemical stability at room temperature and refrigeration conditions, eliminating the unknown degradation impurity at RRT 0.44 and maintaining stability for at least one month at 25°C/60% RH and nine months at 2°C - 8°C.
Implementation Method 1
a pharmaceutically acceptable buffer... wherein the pH of the solution is from 3.0 to 6.0
Implementation Method 2
0.5 mg/ml to 2.4 mg/ml xanthan gum
Data Source
AI summary
An oral pharmaceutical solution comprising hydroxycarbamide as active ingredient and an aqueous carrier comprising a pharmaceutically acceptable buffer and 0.5 mg/ml to 2.4 mg/ml xanthan gum, wherein the pH of the solution is from 3.0 to 6.0.