Hydroxycarbamide Oral Solution With pH-Controlled Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a lack of a stable oral solution of hydroxycarbamide for the treatment of sickle cell disease, particularly in children under 2 years of age, due to variability in maximum tolerated dose and difficulties in administering solid forms, and existing formulations are not stable enough to meet regulatory standards for shelf life and degradation limits.
Innovation Solution
A stable aqueous hydroxycarbamide solution is formulated with a pH adjuster such as sodium hydroxide, potassium hydroxide, or sodium carbonate to maintain a pH between 6.1 and 7.1, along with optional preservatives, viscosity modifiers, and flavorings, ensuring stability for at least 12 months at 2-8°C and up to one month at ambient temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If hydroxycarbamide is formulated as an oral solution, then dosing precision and ease of administration are improved, but chemical stability deteriorates due to hydrolysis in aqueous environment
Solution Approach 1:
The patent applies parameter changes by adjusting the pH of the aqueous solution to a specific range (pH 5.5-6.5) to minimize hydrolysis of hydroxycarbamide. This pH optimization resolves the contradiction by maintaining chemical stability while preserving the dosing precision benefits of liquid formulation. The patent also explores temperature parameters to further stabilize the solution.
Solution Approach 2:
The patent introduces buffer substances as intermediaries to maintain stable pH conditions in the aqueous solution. These buffers act as mediators that prevent pH fluctuations which would otherwise accelerate hydrolysis, thereby preserving chemical stability while allowing the solution form to provide accurate dosing.
2Stability of the object's composition
If hydroxycarbamide is formulated as solid capsules or tablets, then chemical stability is improved, but ease of administration and dosing individualization deteriorate
Solution Approach 1:
The patent transforms the physical state parameter from solid to liquid, creating an oral solution formulation. This parameter change enables easy administration to pediatric patients and those with dysphagia, while the solution is stabilized through pH control to maintain acceptable chemical stability.
Solution Approach 2:
The patent applies local quality by providing customized dosing solutions for specific patient populations (children, dysphagia patients) who have different administration needs. The liquid formulation allows for individualized dosing tailored to each patient's requirements, while solid formulations remain suitable for other patient groups.
3Stability of the object's composition
If buffer substances are added to stabilize hydroxycarbamide solution, then chemical stability is improved, but shelf life is insufficient to meet regulatory standards
Solution Approach 1:
The patent optimizes multiple parameters including pH (targeting 5.5-6.5), buffer concentration, and storage temperature to achieve a shelf life of at least 12 months. This multi-parameter optimization resolves the contradiction by extending the duration of stability to meet regulatory requirements while maintaining chemical stability throughout the shelf life period.
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 provides stable hydroxycarbamide formulations that allow for accurate individualized dosing, are palatable for pediatric patients, and meet regulatory standards for degradation levels, with carbamoyloxyurea content below 0.5% w/v, suitable for treating sickle cell disease.
Implementation Method 1
a pH adjuster being one of sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate, or a mixture of one or more of these substances; wherein: the solution is controlled to have a pH of between 6.1 and 7.1
Data Source
AI summary
The present invention provides a stable aqueous hydroxycarbamide solution comprising: hydroxycarbamide; a pH adjuster being sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate, or a mixture of one or more of these substances; and optionally a preservative being a base of methyl hydroxybenzoate and/or ethyl hydroxybenzoate; wherein: the solution is controlled to have a pH of between 6.1 and 7.1. The solution of the present invention is beneficial as compared to solutions according to the prior art in that it can be safely stored at ambient temperatures for prolonged periods of time without significant degradation.