Dasatinib Formulation with Controlled Disintegrant
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Solution Overview
Problem
Existing formulations of dasatinib do not provide clear guidance on disintegrant content and particle size, leading to unpredictable dissolution and pharmacokinetic profiles, and existing patents lack detailed particle size measurement techniques.
Innovation Solution
An oral dosage form of dasatinib with a controlled disintegrant content ratio (0.3:1.0 to 1.0:1.0) and particle size (D90 of 50 to 100 µm) using croscarmellose sodium, achieving a dissolution profile of 45-70% in 60 minutes and pharmacokinetic similarity to Sprycel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If disintegrant content is increased to enhance dissolution, then dissolution rate should improve, but dissolution of dasatinib actually decreases within a specific range
Solution Approach 1:
The patent applies parameter changes by precisely controlling the disintegrant content within a specific range (0.3:1.0 to 1.0:1.0 ratio) rather than simply increasing it. This optimized parameter range resolves the contradiction by finding the optimal point where dissolution rate is enhanced without causing the unexpected decrease observed at higher disintegrant levels.
2Speed
If disintegrant content is increased to enhance dissolution, then dissolution should improve, but pharmacokinetic profiles become unpredictable
Solution Approach 1:
The patent employs parameter changes by defining a specific disintegrant content range (0.3:1.0 to 1.0:1.0 ratio) that optimizes both dissolution rate and pharmacokinetic profile consistency. This precise parameter control prevents the unpredictability associated with higher disintegrant levels while still enhancing dissolution.
3Speed
If particle size is decreased to enhance dissolution, then dissolution should improve, but compression properties may deteriorate
Solution Approach 1:
The patent applies parameter changes by specifying an optimal particle size range (D90 of 50 to 100 µm) that balances dissolution enhancement with maintained compression properties. This controlled parameter range resolves the contradiction by avoiding both excessively large particles (poor dissolution) and excessively fine particles (poor compression).
Data Source
Figure 1~2
AI summary
The present invention relates to an oral dosage form comprising dasatinib, or a pharmaceutically acceptable salt thereof. In particular, the present invention relates to an oral dosage form comprising dasatinib, or a pharmaceutically acceptable salt thereof, wherein the amount of disintegrant present is controlled so as to provide desirable dissolution and / or pharmacokinetic profiles.