Ibrutinib Tablet Composition for High Drug Load and Hardness
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Solution Overview
Problem
There is a need for alternative formulations of the BTK inhibitor ibrutinib that provide improved stability, efficacy, and patient compliance, particularly in the treatment of hematological malignancies and autoimmune diseases.
Innovation Solution
A pharmaceutical composition comprising ibrutinib with specific ratios of microcrystalline cellulose and crospovidone as excipients, formulated using a dry granulation method such as roller compaction, to create high-load solid tablet formulations with enhanced properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high-load solid tablet formulations of ibrutinib are prepared using conventional formulation methods, then the drug loading is increased, but the tablet hardness and stability are insufficient
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using amorphous ibrutinib instead of crystalline form, and by optimizing the excipient ratios (microcrystalline cellulose 10-30%, crospovidone 5-20%). These parameter changes enable high drug loading (50-80% w/w) while maintaining adequate tablet hardness and stability.
2Quantity of substance
If high-load tablet formulations are prepared, then the drug concentration is increased, but sticking during tableting occurs
Solution Approach 1:
The patent introduces specific excipients as intermediaries: microcrystalline cellulose (10-30% w/w) acts as a filler and binding agent, while crospovidone (5-20% w/w) serves as a disintegrant. These intermediaries facilitate the tableting process by preventing sticking while maintaining high ibrutinib concentration (50-80% w/w) in the formulation.
3Device complexity
If conventional formulations are used, then the formulation is simple, but the bioavailability and efficacy are limited
Solution Approach 1:
The patent achieves improved bioavailability through parameter changes: using amorphous ibrutinib (which has superior solubility and dissolution rate compared to crystalline form), optimizing excipient concentrations, and controlling particle size. These changes enhance drug release and absorption while maintaining formulation simplicity with only two excipients.
Data Source
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AI summary
Disclosed are formulations/compositions comprising a BTK inhibitor, particularly ibrutinib (Formula I) as well as processes for preparing such formulations/compositions and methods of treatment of a disease or condition that comprises the use of such formulations/compositions.