Plasticizer-Free Ibrutinib Form C Coated Tablet Composition
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Solution Overview
Problem
The use of a common film coating composition promotes polymorphic conversion from ibrutinib Form C to Form A, which is less stable and has lower solubility, and the presence of surfactants like sodium lauryl sulfate can cause gastrointestinal irritation and stability issues.
Innovation Solution
A film-coated tablet composition of ibrutinib Form C using hydroxypropylmethylcellulose and hydroxypropylcellulose as film formers without plasticizers, ensuring stability and ease of swallowing, while avoiding surfactants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If a common film coating composition containing plasticizer is used, then the tablet coating provides good film formation and flexibility, but it promotes polymorphic conversion from ibrutinib Form C to Form A
Solution Approach 1:
The patent removes plasticizer from the film coating composition to prevent polymorphic conversion of ibrutinib from Form C to Form A. This extraction of the harmful component (plasticizer) resolves the contradiction by eliminating the cause of instability while maintaining coating functionality through alternative plasticizing mechanisms or formulation adjustments.
Solution Approach 2:
The patent changes the chemical composition parameters of the film coating by eliminating plasticizer and using alternative polymers (hydroxypropylmethylcellulose and hydroxypropylcellulose) in specific ratios. This parameter change prevents polymorphic conversion while maintaining adequate film formation properties through modified polymer selection and concentration optimization.
2Ease of operation
If a film coating is applied to improve swallowing, then the tablet ease of swallowing is improved, but polymorphic conversion occurs
Solution Approach 1:
The patent extracts plasticizer from the coating formulation to prevent polymorphic conversion while maintaining film coating functionality. This allows the coating to provide improved swallowability without causing the harmful polymorphic conversion effect.
Solution Approach 2:
The patent uses a composite polymer system consisting of hydroxypropylmethylcellulose and hydroxypropylcellulose in specific ratios to achieve both film formation quality and stability. This composite material approach provides the necessary coating properties for improved swallowability while preventing polymorphic conversion through the synergistic effects of the polymer combination.
3Ease of manufacture
If surfactants like sodium lauryl sulfate are added to coating composition, then the coating application is improved, but gastrointestinal irritation and stability issues occur
Solution Approach 1:
The patent removes surfactants from the film coating composition to eliminate gastrointestinal irritation and stability issues. This extraction of harmful substances resolves the contradiction by eliminating the cause of adverse effects while maintaining coating application quality through alternative formulation approaches.
Solution Approach 2:
The patent uses alternative polymers (hydroxypropylmethylcellulose and hydroxypropylcellulose) as intermediary substances that can provide coating application benefits without the harmful effects of surfactants. These intermediary materials serve as substitutes that achieve the desired coating properties through different mechanisms.
Data Source
Figure 1
AI summary
The present invention relates to a coated tablet composition comprising ibrutinib and one or more pharmaceutically acceptable excipients, characterized in that: • Ibrutinib is form C, having characteristic peaks in the X-ray powder diffraction pattern at the following 2 theta (± 0.2) angles: 6.9º, 18.2º, 19.2º, 19.6º and 23.0º, measured using a Cu Kα radiation; and • The coating is free of plasticizer. The invention further relates to the use of said composition as a medicament, particularly in the treatment of chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), Waldenstrӧm's macroglobulinaemia (WM) and chronic graft-versus-host disease (cGVHD).