Axitinib Form IV Tablet Dissolution Control
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Solution Overview
Problem
Formulating an immediate release tablet composition of axitinib form IV that is stable, suitable for commercial production, and bioequivalent to the marketed product Inlyta®, which faces challenges due to higher bioavailability and dissolution profiles not matching the reference product.
Innovation Solution
An immediate release tablet composition comprising axitinib form IV with a specific XRPD pattern and one or more pharmaceutically acceptable excipients, exhibiting a dissolution rate between 40% and 70% in 30 minutes when tested in a USP apparatus II, ensuring bioequivalence to Inlyta®.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If axitinib form IV is used in tablet composition, then dissolution rate and bioavailability are improved, but bioequivalence to reference product is lost
Solution Approach 1:
The patent applies parameter changes by carefully controlling the dissolution rate of axitinib form IV within a specific range (40-70% in 30 minutes) to achieve the optimal balance between improved dissolution/bioavailability and maintenance of bioequivalence to the reference product. This quantitative parameter control resolves the contradiction by finding the precise operational window where both benefits are achieved.
2Quantity of substance
If axitinib form IV is used in tablet composition, then aqueous solubility is improved, but stability is worsened
Solution Approach 1:
The patent resolves this contradiction by changing the physical state parameter of axitinib from other crystalline forms to form IV, which has superior aqueous solubility. The formulation process then stabilizes this form through controlled manufacturing conditions and excipient selection, maintaining both the solubility advantage and compositional stability throughout storage and handling.
3Productivity
If dissolution rate is increased to improve bioavailability, then Cmax and AUCt values increase, but bioequivalence to reference product is lost
Solution Approach 1:
The patent applies parameter changes by establishing a precise dissolution rate window (40-70% in 30 minutes) that optimizes bioavailability while maintaining bioequivalence. This controlled parameter range ensures that Cmax and AUCt values remain within acceptable ranges for bioequivalence demonstration, resolving the contradiction between improving bioavailability and maintaining manufacturing precision.
Data Source
AI summary
The present invention relates to an immediate release tablet composition comprising axitinib form IV characterized by an XRPD pattern comprising the peaks at about 8.9, 12.0, 14.6, 15.2, 15.7, 17.8, 19.1, 20.6, 21.6, 23.2, 24.2, 24.9, 26.1 and 27.5±0.1 degrees 2θ, when measured with Cu Kα1 radiation and one or more pharmaceutically acceptable excipients, wherein the composition exhibits a dissolution rate between 40% and 70% in 30 minutes when tested in 900 ml 0.01 N hydrochloric acid pH 2.0 at 37° C., 75 rpm in a USP apparatus II.