Racecadotril Aqueous Suspension pH Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current pediatric formulations of racecadotril for treating diarrhea in infants and children are cumbersome, prone to dosing errors, and costly, with challenges in stability and administration due to its insolubility and bitter taste, and difficulty in mixing with other active principles like ondansetron.
Innovation Solution
A stable aqueous suspension of racecadotril with a pH between 3.5 and 5, using buffering agents like sodium citrate and lactic acid, thickening agents such as hydroxyethylcellulose, and suspending agents like xanthan gum, which also incorporates ondansetron for simultaneous administration, ensuring homogeneity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If racecadotril is formulated as a powder suspension for pediatric use, then it can be administered to infants and children, but the dosing becomes complex and error-prone due to the need for multiple unity dosages
Solution Approach 1:
The invention divides the dosing system into segmented units (sachets containing specific amounts of racecadotril) that can be easily combined to achieve different dosages. Each sachet represents a discrete dosing unit, and multiple sachets can be mixed in a single suspension to achieve the required dose based on patient age and weight, simplifying the dosing process while maintaining precision.
Solution Approach 2:
The racecadotril is pre-formulated into granulated powder with specific properties (flowability, stability) and pre-packaged in sachets with predetermined amounts. This preliminary preparation eliminates the need for complex compounding at the point of use, allowing healthcare providers to simply mix the pre-prepared granules with water to create the suspension, thereby simplifying the dosing operation.
2Adaptability or versatility
If racecadotril is formulated as a powder suspension, then it can be administered to pediatric patients, but the price is inherently higher than alternative forms such as syrup
Solution Approach 1:
The invention changes the physical and chemical parameters of the racecadotril formulation by developing a granulated powder with specific characteristics (flowability, stability, solubility properties) that enable cost-effective manufacturing and storage. The granulation process and pH adjustment (to 3.5-5.0) create a formulation that is more stable and easier to manufacture than traditional syrup forms, reducing production costs while maintaining pediatric adaptability.
3Adaptability or versatility
If racecadotril suspension is prepared from powder, then it can be administered to pediatric patients, but strong mixing and quick administration are required to prevent granule settling
Solution Approach 1:
The invention adjusts the pH of the suspension to a specific range (3.5-5.0) and uses granulated powder with controlled particle size and surface properties. These parameter changes create a suspension with improved stability characteristics, reducing the tendency of granules to settle and minimizing the need for vigorous and continuous mixing, thereby simplifying the administration process.
4Ease of operation
If aqueous suspension of racecadotril is prepared, then it can be administered to pediatric patients, but hydrolysis of the ester group can occur leading to degradation into less active compounds
Solution Approach 1:
The invention carefully controls the pH of the aqueous suspension within a specific range (3.5-5.0) to minimize hydrolysis of the ester group in racecadotril. This pH optimization reduces the rate of degradation into less active compounds while still maintaining the drug's solubility and bioavailability. Additionally, the use of granulated powder with controlled properties further enhances stability by reducing the surface area exposed to aqueous environment.
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 allows precise dosing based on age or weight, improved oral bioavailability, reduced toxicity, and stability, with enhanced ease of administration and reduced risk of errors, while maintaining the effectiveness of both active ingredients.
Implementation Method 1
The stable aqueous suspensions of the invention are made possible in particular by carefully adjusting the pH of the suspension. The aqueous suspensions of the invention unexpectedly show stability... wherein said suspension has a pH comprised between 3.5 and 5.
Implementation Method 2
The formulation comprises a stable aqueous suspension of racedotril... using buffering agents like sodium citrate and lactic acid, thickening agents such as hydroxyethylcellulose, and suspending agents like xanthan gum
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a new formulation of an enkephalinase inhibitor, such as racecadotril or dexecadotril, the process for the preparation thereof, and the use thereof in the treatment of diarrhoea.