Mesoporous Silica Drug Loading with Polymer Coating
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Solution Overview
Problem
Current drug delivery systems for poorly soluble drugs face challenges in achieving improved solubility and bioavailability due to limitations in loading capacity and dissolution efficiency, particularly with mesoporous silica materials that exhibit poor flowability and compression properties, and often result in crystalline forms that hinder effective drug release.
Innovation Solution
A pharmaceutical dosage form comprising mesoporous silica particles loaded with a poorly soluble active pharmaceutical ingredient, where the external surfaces are coated with a polymer solid dispersion, enhancing the drug's amorphous or molecularly dispersed state and increasing solubility, specifically for drugs like rivaroxaban and ibuprofen, using methods such as hot melt extrusion or granulation to achieve a higher loading capacity and improved bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If mesoporous silica materials are used to load poorly soluble drugs, then the drug loading capacity is improved, but the flowability and compression properties deteriorate
Solution Approach 1:
A spray-dried dispersion serving as a master batch is introduced as an intermediary component. This master batch contains the poorly soluble drug dispersed in a carrier material, and when mixed with mesoporous silica, it acts as a mediating substance that improves flowability and compression properties while maintaining high drug loading capacity within the mesoporous structure
Solution Approach 2:
The invention creates a composite formulation combining mesoporous silica particles, spray-dried dispersion (master batch), and carrier materials. This composite structure leverages the high surface area of mesoporous silica for drug loading while the spray-dried dispersion and carrier materials provide improved rheological properties for manufacturing
2Productivity
If drugs are loaded inside mesoporous carriers, then the dissolution is improved, but the active ingredient remains in crystallized form on the surface
Solution Approach 1:
The physical state of the drug on the particle surface is changed from crystalline to amorphous through the spray-drying process. The rapid evaporation of solvent during spray drying prevents crystallization, trapping the drug in an amorphous state on the external surfaces, which enhances dissolution while maintaining stability
Solution Approach 2:
Different regions of the particle exhibit different drug states: the internal pores contain drug in a state suitable for controlled release, while the external surfaces contain drug in amorphous form through the spray-dried dispersion, creating local quality differences that optimize both dissolution and stability
3Reliability
If complex formulation methods are used to improve dissolution, then the bioavailability is improved, but the process complexity increases
Solution Approach 1:
Multiple formulation functions are merged into a single spray-dried dispersion master batch. This master batch simultaneously provides drug dispersion, amorphous state maintenance, and flowability improvement, eliminating the need for separate formulation steps and reducing overall process complexity while ensuring reliable bioavailability
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 proposed solution significantly enhances the dissolution profile and bioavailability of poorly soluble drugs by converting crystalline forms to amorphous or molecularly dispersed states, increasing the loading capacity and stability of the active ingredients, leading to improved therapeutic efficacy and formulation efficiency compared to existing products like Xarelto®.
Implementation Method 1
Mesoporous materials have pores within their structures which can be loaded with active ingredients. The drug can be loaded inside of the mesoporous carrier and/or mesoporous matrix
Implementation Method 2
the external surfaces of the mesoporous particles are at least partially covered with a polymer solid dispersion of said active pharmaceutical ingredient, wherein the poorly soluble drug is rivaroxaban and/or ibuprofen
Data Source
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AI summary
The present invention is directed to a new pharmaceutical dosage form comprising mesoporous particles loaded with a poorly soluble active pharmaceutical ingredient, said particles being at least partially, preferably homogeneously, covered with a polymer solid dispersion.