High-Load Ibrutinib Tablet Formulation for Bioavailability
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Solution Overview
Problem
There is a need for alternative formulations of the BTK inhibitor ibrutinib that provide improved stability and efficacy in treating hematological malignancies and other conditions associated with BTK activity.
Innovation Solution
A pharmaceutical composition comprising ibrutinib with specific ratios of mannitol and crospovidone, along with additional excipients like polyvinylpyrrolidone, sodium lauryl sulfate, colloidal silicon dioxide, and magnesium stearate, prepared using a wet granulation method, to create a high-load solid tablet formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulations of ibrutinib are used, then the drug can be administered, but the bioavailability and therapeutic efficacy are insufficient
Solution Approach 1:
The patent changes the formulation parameters by incorporating specific excipients (mannitol, crospovidone, polyvinylpyrrolidone, sodium lauryl sulfate, colloidal silicon dioxide, and magnesium stearate) in optimized ratios. This modifies the physical and chemical properties of the drug formulation to enhance dissolution rate and bioavailability, thereby improving therapeutic efficacy without changing the active ingredient itself.
Solution Approach 2:
The patent creates a composite pharmaceutical formulation by combining ibrutinib with multiple excipients that serve different functions: mannitol and crospovidone as fillers and disintegrants, polyvinylpyrrolidone as a binder, sodium lauryl sulfate as a surfactant to enhance dissolution, colloidal silicon dioxide as a flow agent, and magnesium stearate as a lubricant. This composite approach synergistically improves the overall performance of the formulation.
2Duration of action of moving object
If high-load solid tablet formulation is developed, then once-daily dosing is achieved, but the formulation complexity increases
Solution Approach 1:
The patent divides the formulation into distinct functional components with specific roles: fillers (mannitol, crospovidone), binders (polyvinylpyrrolidone), surfactants (sodium lauryl sulfate), flow agents (colloidal silicon dioxide), and lubricants (magnesium stearate). This segmentation allows each excipient to be optimized for its specific function while maintaining overall formulation simplicity and manufacturability.
Solution Approach 2:
The patent optimizes the concentration parameters of each excipient to achieve the desired once-daily dosing profile. By carefully controlling the ratios and amounts of each component, the formulation achieves sustained release and improved bioavailability that support extended dosing intervals, while the standardized preparation method keeps the process manageable.
Data Source
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AI summary
Disclosed are formulations/compositions comprising a BTK inhibitor, particularly ibrutinib: (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.