Selexipag Form P Tablet with Controlled Particle Size
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Solution Overview
Problem
Current tablet formulations of selexipag face challenges with low solubility, poor dissolution profiles, and stability issues, leading to suboptimal bioavailability and physicochemical properties.
Innovation Solution
A tablet formulation comprising selexipag form P with a particle size between 1 µm to 150 µm, combined with suitable excipients like hydroxypropyl cellulose, D-mannitol, sodium starch glycolate, and magnesium stearate, using a wet granulation process to enhance dissolution, flowability, and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If selexipag is formulated in conventional tablet forms, then the formulation can be manufactured, but solubility and dissolution profile remain poor
Solution Approach 1:
The patent applies particle size reduction to change the physical parameters of selexipag, reducing d(0.9) particle size to 1-150 μm. This parameter change increases the surface area and improves both solubility and dissolution profile, directly resolving the contradiction between manufacturing feasibility and poor dissolution characteristics
Solution Approach 2:
The patent creates a composite formulation combining selexipag with specific excipients (hydroxypropyl cellulose, D-mannitol, sodium starch glycolate, magnesium stearate) in optimized ratios. This composite approach improves solubility and dissolution while maintaining manufacturability, addressing the technical contradiction
2Quantity of substance
If selexipag particle size is reduced to improve solubility, then dissolution improves, but manufacturing precision and flowability become challenging
Solution Approach 1:
The patent optimizes particle size parameters to a specific range (d(0.9) of 1-150 μm) that balances improved solubility with acceptable flowability and manufacturing precision. This parameter optimization resolves the contradiction by finding the optimal point where dissolution benefits are achieved without compromising content uniformity
Solution Approach 2:
The patent applies different functional characteristics to different components of the formulation. The selexipag particles are specifically sized for dissolution, while excipients are selected for their specific functions in maintaining flowability and content uniformity during manufacturing. This localized functional assignment resolves the contradiction between solubility improvement and manufacturing precision
3Ease of manufacture
If conventional formulation methods are used, then manufacturing is simple, but stability and bioavailability are insufficient
Solution Approach 1:
The patent develops a composite formulation with specifically selected excipients that work synergistically with selexipag. This composite approach maintains manufacturing simplicity while significantly improving stability and bioavailability, resolving the contradiction between ease of manufacture and formulation effectiveness
Solution Approach 2:
The patent optimizes formulation parameters including excipient ratios and particle size characteristics to achieve a balance between manufacturing simplicity and improved stability. This parameter optimization allows conventional manufacturing methods to produce stable, high-bioavailability formulations, resolving the technical contradiction
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 achieves improved solubility, bioavailability, and long-term stability, ensuring high physicochemical properties and content uniformity, addressing the limitations of prior art.
Implementation Method 1
selexipag form P has a d (0.9) particle size between 1 μm to 150 μm
Implementation Method 2
improved the dissolution profile
Implementation Method 3
using an effective process
Implementation Method 4
amorphous selexipag was only described in one single experiment using 1,3,5-trimethylbenzene as solvent
Data Source
AI summary
The present invention relates to a tablet formulation comprising selexipag form P, wherein selexipag form P has a d (0.9) particle size between 1 µm to 150 µm. Furthermore, the tablet is obtained using an effective process.