Apixaban Soft-Gel Capsule Composition for Solubility and Uniform Dosing
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Solution Overview
Problem
Apixaban, a potent anticoagulant with low water solubility, presents challenges in achieving uniform distribution, dissolution rate, and bioavailability in pharmaceutical formulations, particularly in solid dosage forms, and has an unpleasant taste that can lead to non-compliance, necessitating the development of stable and effective oral compositions.
Innovation Solution
Stable pharmaceutical compositions of apixaban solubilized in a pharmaceutically acceptable carrier system comprising solubilizing agents and optional excipients, encapsulated in soft-gelatin capsules for rapid release and improved bioavailability, with a dissolution profile comparable to commercial tablets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If apixaban is formulated in solid dosage forms, then manufacturing and handling are simplified, but uniform distribution and dissolution rate are compromised due to low water solubility
Solution Approach 1:
The patent changes the physical state of apixaban from solid to liquid form within the capsule, which fundamentally alters its dissolution behavior. The liquid formulation allows the poorly water-soluble drug to be dispersed in a liquid carrier system, eliminating the dissolution barrier present in solid dosage forms while maintaining manufacturing feasibility through encapsulation.
Solution Approach 2:
The invention creates a composite liquid formulation system combining apixaban with pharmaceutically acceptable carriers, solubilizing agents, and excipients. This composite approach allows the insoluble drug to be uniformly distributed and stabilized in liquid form, achieving both manufacturability and reliable dissolution performance that neither solid form nor simple solutions could provide alone.
2Reliability
If apixaban is administered in high potency doses, then therapeutic efficacy is improved, but content uniformity and handling restrictions become more challenging
Solution Approach 1:
The patent uses liquid filling technology to precisely deliver the exact liquid formulation containing the precise amount of apixaban into each capsule. This liquid filling approach provides superior dose accuracy compared to solid dosage forms, as the liquid can be metered and filled with high precision, ensuring content uniformity even at high potency doses.
Solution Approach 2:
By transitioning from solid to liquid formulation, the patent eliminates the challenges of distributing and handling high-potency solid particles. The liquid state allows for easier and more precise measurement, mixing, and filling operations, improving both content uniformity and handling safety while maintaining the high therapeutic potency of apixaban.
3Manufacturing precision
If liquid oral formulations are used to achieve optimal content uniformity, then distribution is improved, but taste masking becomes necessary to ensure patient compliance
Solution Approach 1:
The patent introduces taste-masking excipients and flavoring agents as intermediaries between the bitter apixaban and the patient's taste receptors. These additives form a protective layer or complex with the drug, preventing direct taste perception while maintaining the drug's bioavailability and the liquid formulation's content uniformity advantages.
Solution Approach 2:
The liquid formulation is designed as a composite system that combines apixaban with carriers, solubilizing agents, and taste-masking excipients in specific ratios. This composite approach allows simultaneous achievement of content uniformity through liquid dispersion and taste masking through the combined effect of multiple formulation components, ensuring both manufacturing precision and patient compliance.
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 compositions provide extended stability and bioavailability, ensuring uniform distribution and rapid release of apixaban, enhancing patient compliance and therapeutic efficacy.
Implementation Method 1
apixaban solubilized in a pharmaceutically acceptable carrier system
Implementation Method 2
encapsulated in soft-gelatin capsules for rapid release and improved bioavailability
Data Source
AI summary
The present invention relates to stable pharmaceutical compositions comprising apixaban or its pharmaceutically acceptable salts thereof. The present invention further relates to a capsule composition comprising a therapeutically effective amount of apixaban solubilized or dispersed in a pharmaceutically acceptable carrier, wherein the therapeutically effective amount of apixaban ranges from about 0.5 mg/unit dosage form to about 50 mg/unit dosage form. The present invention also provides manufacturing processes thereof and use of the said compositions for prevention, treatment or prophylaxis of disorders in human patients in need thereof.