Apixaban Solid Composition Wet Granulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current apixaban tablet production is costly due to high compressibility issues and poor particle homogeneity, leading to challenges in quality control and absorption, particularly with small particle sizes requiring complex and expensive processing.
Innovation Solution
A novel apixaban solid composition with a particle size D90 greater than 89 μm, prepared using a wet granulation method with a binder like povidone, which enhances granulation capability, compressibility, and stability, allowing for more efficient and cost-effective industrial production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If small particle size apixaban is used to improve dissolution rate, then dissolution rate is improved, but production cost increases and compressibility decreases
Solution Approach 1:
The patent changes the particle size parameter from small (conventional) to large (D90 > 89 μm), which counterintuitively improves both dissolution rate and manufacturability. This parameter inversion resolves the contradiction by showing that larger particles can achieve fast dissolution through proper formulation while significantly reducing production costs and improving compressibility.
Solution Approach 2:
The patent applies different particle size specifications to different components of the formulation. The apixaban active ingredient uses large particles (D90 > 89 μm) for cost-effectiveness, while other excipients may use different particle sizes optimized for their specific functions. This local differentiation resolves the contradiction by allowing each component to be optimized independently.
2Ease of manufacture
If large particle size apixaban is used to reduce production cost, then production cost decreases, but dissolution rate slows down
Solution Approach 1:
The patent creates a composite tablet formulation containing large particle apixaban combined with specific excipients including disintegrants (croscarmellose sodium, sodium starch glycolate), surfactants (sodium lauryl sulfate), and binders. This composite structure allows the large particles to be processed easily while the excipients work synergistically to maintain fast dissolution rates, thus resolving the contradiction between particle size and dissolution performance.
Solution Approach 2:
The patent introduces intermediary substances (excipients such as disintegrants and surfactants) that mediate between the large particle apixaban and the dissolution medium. These intermediaries facilitate rapid dissolution of the large particles without requiring size reduction, thereby resolving the contradiction between large particle size and dissolution rate.
3Ease of manufacture
If wet granulation method is used to improve granulation capability, then granulation capability improves, but process complexity increases
Solution Approach 1:
The patent optimizes key process parameters of wet granulation including binder concentration (2-10% w/w), granulation time (5-30 minutes), and moisture content (5-15% w/w). By establishing specific parameter ranges, the patent simplifies process control and reduces complexity while maintaining excellent granulation capability and tablet compressibility.
Solution Approach 2:
The patent performs preliminary blending of excipients before wet granulation to ensure uniform distribution of components. This preliminary action prevents processing issues during granulation and simplifies the overall process by pre-establishing material homogeneity, thereby reducing process complexity while improving granulation capability.
4Strength
If apixaban particle size is increased to improve compressibility, then compressibility improves, but particle surface area decreases
Solution Approach 1:
The patent formulates a composite tablet system where large particle apixaban (providing good compressibility) is combined with excipients that contribute additional surface area and dissolution active sites. The composite structure compensates for the reduced particle surface area while maintaining excellent compressibility and tablet strength.
Solution Approach 2:
The patent uses excipients as functional copies or substitutes that provide surface area and dissolution pathways that would otherwise be provided by smaller apixaban particles. These excipient particles compensate for the reduced surface area of large apixaban particles, maintaining dissolution performance while allowing use of larger, more compressible particles.
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 results in a faster dissolution rate, higher absorption, and improved stability of the apixaban tablets, simplifying the production process and ensuring consistent quality, making it suitable for commercial production.
Implementation Method 1
granulating apixaban by using a wet granulation method to get a binder solution
Implementation Method 2
dissolving apixaban and a binder in a wetting agent to get a binder solution
Data Source
AI summary
The present invention provided an apixaban solid composition and a preparation method thereof. The method comprises granulating apixaban by wet granulation, wherein the apixaban has a particle size D90 more than 89 μm.