Apixaban Solid Dispersion Composition for Solubility and Uniformity
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Solution Overview
Problem
Existing apixaban pharmaceutical compositions face challenges with low solubility, low bioavailability, and poor content uniformity, which affect their efficacy and stability.
Innovation Solution
A pharmaceutical composition comprising apixaban and pharmaceutically acceptable polymers, prepared via hot-melt extrusion, which includes specific ratios of apixaban, polymers like Soluplus, diluents such as dibasic anhydrous calcium phosphate and microcrystalline cellulose, and excipients, to enhance solubility, bioavailability, and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If apixaban is administered in conventional crystalline form, then manufacturing is simple, but solubility is poor and bioavailability is low
Solution Approach 1:
The patent transforms apixaban from crystalline to amorphous form, changing its physical state parameters. This amorphous form is then incorporated into solid dispersion formulations with polymers, fundamentally altering the dissolution behavior and bioavailability profile while maintaining manufacturing feasibility through established granulation and compression processes
Solution Approach 2:
The invention creates composite pharmaceutical formulations by combining amorphous apixaban with polymers and excipients in solid dispersion systems. These composite materials enhance solubility and bioavailability through the synergistic effects of the polymer matrix and amorphous active ingredient, while remaining manufacturable using conventional tablet compression equipment
2Device complexity
If apixaban is administered in conventional crystalline form, then formulation is simple, but dissolution rate is slow
Solution Approach 1:
The patent fundamentally changes the physical state of apixaban from crystalline to amorphous, which eliminates the slow dissolution kinetics associated with crystal lattice structures. The amorphous form provides immediate dissolution upon contact with gastrointestinal fluids, dramatically increasing the dissolution rate without requiring complex formulation strategies
Solution Approach 2:
The invention utilizes the phase transition from crystalline to amorphous state of apixaban to achieve rapid dissolution. The amorphous phase lacks the ordered crystal structure, allowing for immediate solvation and dissolution in aqueous environments, thereby achieving fast dissolution rates with relatively simple solid dispersion formulations
3Quantity of substance
If low dose of apixaban is targeted, then therapeutic efficacy is optimized, but content uniformity becomes difficult to achieve
Solution Approach 1:
The patent changes the physical state of apixaban to amorphous form, which improves its flow properties and homogeneity during granulation and compression processes. This physical transformation enables better distribution of the low dose active ingredient throughout the tablet matrix, achieving content uniformity that would be difficult with crystalline form at low doses
Solution Approach 2:
The invention creates homogeneous solid dispersion formulations where amorphous apixaban is uniformly distributed within the polymer and excipient matrix. This homogeneous distribution ensures consistent dosing and content uniformity even at low dose levels, as the amorphous active ingredient integrates seamlessly with the formulation components during manufacturing
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 achieves high solubility, bioavailability, and chemical stability, ensuring uniformity and long-term shelf life, with improved dissolution rates and reduced thermal degradation risks.
Implementation Method 1
hot-melt extrusion is one of the methods for preparing apixaban formulations wherein apixaban is in the amorphous form
Implementation Method 2
apixaban is in the amorphous form and processes for preparing an amorphous form of apixaban
Data Source
AI summary
The present invention relates to solid pharmaceutical compositions comprising apixaban or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable polymer. The composition is obtained by using an effective process.