Apixaban Orally Disintegrating Composition for Consistent Dissolution
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Solution Overview
Problem
Existing apixaban formulations face challenges with inconsistent dissolution and absorption due to particle size and manufacturing process, particularly for patients with dysphagia, leading to reduced patient compliance and less than optimal exposure.
Innovation Solution
Development of an orally disintegrating tablet formulation comprising specific ratios of apixaban with mannitol, starch, lactose, microcrystalline cellulose, crospovidone, sodium lauryl sulfate, magnesium stearate, and peppermint flavor, achieving consistent dissolution and absorption, with disintegration times under 3 minutes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If immediate release tablet formulation is used, then dissolution rate can be improved, but particle size control and manufacturing process complexity increase
Solution Approach 1:
The patent changes the particle size parameter of apixaban to D90 ≤ 89 μm through micronization, which directly improves dissolution rate. This parameter change resolves the contradiction by achieving faster dissolution without requiring complex manufacturing processes, as the fine particles can be directly compressed into tablets.
Solution Approach 2:
The patent performs preliminary micronization of apixaban particles before formulation to achieve the required D90 ≤ 89 μm size. This preliminary action ensures consistent dissolution rate is achieved upfront, eliminating the need for complex manufacturing process controls during tablet production.
2Ease of operation
If orally disintegrating dosage form is developed, then patient compliance can be improved, but formulation stability becomes more challenging
Solution Approach 1:
The patent uses a composite formulation containing apixaban, mannitol, starch, lactose, microcrystalline cellulose, crospovidone, and other excipients. This composite material approach achieves both oral disintegration for improved patient compliance and formulation stability through the synergistic effects of multiple components that maintain structural integrity while enabling rapid disintegration.
Solution Approach 2:
The patent incorporates superdisintegrants like crospovidone and starch in specific proportions (5-10% and 20-30% respectively) to create local disintegration zones within the tablet. This local quality approach ensures the tablet remains stable during storage but disintegrates rapidly upon contact with saliva, resolving the contradiction between stability and ease of administration.
3Manufacturing precision
If finer apixaban particles are used, then dissolution consistency can be improved, but manufacturing cost increases
Solution Approach 1:
The patent adopts the particle size specification (D90 ≤ 89 μm) that has been proven effective in previously approved apixaban formulations. By copying this established parameter, the patent achieves dissolution consistency without incurring excessive manufacturing costs, as the micronization process is already optimized in the industry.
Solution Approach 2:
The patent uses direct compression of micronized particles without requiring complex granulation or coating processes. This approach treats the tablet formulation as a simple compressed powder mixture, eliminating the need for expensive manufacturing equipment and processes while maintaining dissolution consistency through particle size control.
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 provides bioequivalent pharmacokinetic parameters to immediate release tablets, ensuring consistent drug exposure and improved patient compliance by allowing administration without water, suitable for patients with swallowing difficulties.
Implementation Method 1
orally disintegrating tablet formulation... with disintegration times under 3 minutes
Implementation Method 2
crospovidone, starch... disintegrating excipients
Implementation Method 3
mannitol, starch, lactose, microcrystalline cellulose... fillers
Implementation Method 4
sodium lauryl sulfate... surface active agent
Implementation Method 5
magnesium stearate... lubricant
Data Source
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AI summary
The present invention relates to an orally disintegrating pharmaceutical dosage forms of apixaban or a pharmaceutically acceptable salt or prodrug thereof. The present invention specifically relates to a stable orally disintegrating pharmaceutical composition comprising apixaban and one or more pharmaceutically acceptable excipients. Further, the present invention relates to an orally disintegrating dosage form comprising apixaban, at least one disintegrating excipient and optionally one or more pharmaceutically acceptable excipients for treatment of disorders associated with Factor Xa.