Polydextrose Solid Dispersion for Water-Insoluble Drug Bioavailability
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Solution Overview
Problem
Existing pharmaceutical compositions with solid dispersions fail to adequately enhance the bioavailability of water-insoluble active principles due to low solubility issues along the gastrointestinal tract, with conventional methods like micronization and solvent-based approaches being costly and environmentally problematic, and high-temperature methods compromising chemical stability.
Innovation Solution
A novel pharmaceutical composition featuring a solid dispersion with a polymer matrix comprising a blend of polydextrose and another polymer, where both polymers constitute continuous phases, with polydextrose making up at least 20% of the matrix, promoting disintegration in an aqueous medium and improving bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the solvent approach is used to prepare solid dispersions, then the active principle can be solubilized in the matrix, but the process becomes complex and costly with environmental and health problems due to solvent treatment
Solution Approach 1:
The patent removes the solvent from the preparation process entirely, using a melt approach where the active principle is incorporated into the polydextrose matrix at elevated temperatures without requiring solvent dissolution. This eliminates the complex solvent treatment steps while achieving the desired solid dispersion.
Solution Approach 2:
The patent replaces the chemical/solvent-based dissolution mechanism with a thermal/melt-based incorporation mechanism. The active principle is dissolved in the molten polydextrose matrix and then trapped in the amorphous state upon cooling, substituting the solvent role with a melt phase.
2Ease of manufacture
If the molten approach is used to prepare solid dispersions, then the process is simpler and avoids solvent problems, but high temperatures affect the chemical stability of the active principle
Solution Approach 1:
The patent modifies the temperature parameters of the melt approach, using controlled elevated temperatures (typically below the decomposition point of the active principle) and rapid cooling to achieve solidification before thermal degradation can occur. This balances process simplicity with chemical stability.
Solution Approach 2:
The patent employs rapid cooling of the molten matrix to quickly pass through the temperature range where thermal degradation could occur, trapping the active principle in the amorphous state before significant thermal damage can happen. This 'rushing through' the critical temperature zone minimizes stability issues.
3Quantity of substance
If conventional solid dispersions are used, then the active principle is dispersed in the matrix, but the solubility remains low along the gastrointestinal tract resulting in poor bioavailability
Solution Approach 1:
The patent changes the physical state parameter of the polydextrose matrix from crystalline to amorphous through controlled cooling of the melt. This amorphous state creates a more favorable environment for maintaining the active principle in a solubilized state during gastrointestinal transit, significantly improving apparent solubility and bioavailability.
Solution Approach 2:
The patent creates a composite solid dispersion system where the active principle is incorporated within the amorphous polydextrose matrix, forming a new material system with enhanced solubility properties compared to the pure active principle or conventional crystalline dispersions.
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 composition effectively increases the bioavailability of active principles by accelerating disintegration in the stomach, reducing the risk of precipitation and improving solubility, as demonstrated by increased dissolution rates and bioavailability in clinical studies.
Implementation Method 1
polydextrose, in the form of a continuous polydextrose phase, in order to promote the disintegration of the composition in an aqueous medium
Implementation Method 2
Pharmaceutical compositions in the form of solid dispersions of active principles are well known to those skilled in the art. They are generally used to improve the solubility of active principles
Data Source
AI summary
The present invention relates to a solid pharmaceutical composition comprising a solid dispersion containing at least one active principle and a pharmaceutically acceptable polymer matrix,a characterized in that said pharmaceutically acceptable polymer matrix comprises a blend of (i) polydextrose, in the form of a continuous polydextrose phase, in order to promote the disintegration of the composition in an aqueous medium, and (ii) at least one polymer other than polydextrose, in the form of a continuous phase of this polymer, whereby the polydextrose is in a concentration of at least 20 wt % and the at least one polymer other than polydextrose is in a concentration of at least 20 wt % in relation to the total weight of said pharmaceutically acceptable polymer matrix.