Risperidone Aqueous Solution Stability Using Amino Acids
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Solution Overview
Problem
The stability of aqueous solutions of Risperidone is compromised by the use of polyhydric alcohols like sorbitol, which induce decomposition, and existing solutions lack long-term stability confirmation.
Innovation Solution
A stable, high viscosity aqueous oral solution of Risperidone is formulated using amino acids such as glutamic acid or glycine and polymers like hydroxypropyl-methylcellulose (HPMC) without buffering agents, excluding polyhydric alcohols and incorporating antimicrobial agents like benzoic acid to maintain pH and enhance viscosity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If polyhydric alcohols (sorbitol, propylene glycol) are used in the aqueous solution, then the solution can be prepared with conventional excipients, but the stability of Risperidone is compromised due to decomposition induced by polyhydric alcohols
Solution Approach 1:
The patent removes polyhydric alcohols (sorbitol, propylene glycol) from the formulation entirely, extracting the harmful component that causes Risperidone decomposition while maintaining the aqueous solution structure with alternative excipients
Solution Approach 2:
The patent changes the pH parameter of the solution to a slightly acidic range (pH 3.0-5.0) and eliminates buffering agents, creating optimal conditions for Risperidone stability without requiring polyhydric alcohols for solubility enhancement
2Ease of operation
If buffering agents are used to maintain pH, then the pH can be controlled within desired limits, but the solution becomes more complex and may interfere with long-term stability
Solution Approach 1:
The patent removes buffering agents from the formulation, eliminating the complexity associated with pH control systems while achieving stable pH through the inherent properties of the aqueous solution and selected excipients
Solution Approach 2:
The formulation achieves self-regulating pH stability through the natural buffering capacity of the aqueous solution and excipients, without requiring additional buffering agents to maintain pH within the optimal range
3Adaptability or versatility
If polyhydric alcohols are used as excipients, then the solution can be formulated with common ingredients, but long-term stability cannot be confirmed due to decomposition
Solution Approach 1:
The patent removes polyhydric alcohols from the formulation, eliminating the component that prevents long-term stability confirmation and enables demonstration of stability over extended storage periods
Solution Approach 2:
The patent creates a composite aqueous formulation combining Risperidone with specifically selected excipients (hydroxypropyl methylcellulose, polysorbate 80, sodium benzoate) that work synergistically to ensure long-term stability without polyhydric alcohols
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 achieves long-term stability and easier oral administration by maintaining pH within optimal ranges and eliminating decomposition issues, ensuring Risperidone's stability and efficacy.
Implementation Method 1
The amino acids, which are used in the present invention, are components of everyday's alimentation and natural components of the human body. Their use in the composition of the aqueous solution of Risperidone, eliminates / substitutes the need for buffering agents in order to maintain pH within desirable limits.
Implementation Method 2
the composition also contains common excipients for the preparation of oral solutions such as hydroxypropyl-methylcellulose (HPMC) or hydroxypropyl-cellulose (HPC), in rate between 0,01% and 1,0% w/v, in order to increase the viscosity of the solution and to make oral administration easier.
Implementation Method 3
The optimum antimicrobial action of benzoic acid in aqueous solutions depends on the pH range of the preparations of the present invention. The optimum antimicrobial action of benzoic acid, according to the international bibliography, appears in solutions having pH ranging between 2,5 and 4,5.
Data Source
AI summary
A pharmaceutical composition for the preparation of an aqueous oral solution, which contains Risperidone as the active ingredient and makes use of the amino acids glutamic acid or glycine as regulators / stabilizing agents of the oral solution. Moreover, the composition contains hydroxypropyl-methylcellulose (HPMC) or hydroxypropyl-cellulose (HPC) as agents that increase the viscosity of the aqueous solution and excludes the use of polyhydric alcohols.