Avatrombopag Lactose Anhydrous Formulation for Direct Compression
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Solution Overview
Problem
Existing formulations of avatrombopag maleate suffer from low solubility, stability, and compressibility issues, necessitating a new formulation and process that addresses these challenges.
Innovation Solution
The use of avatrombopag maleate combined with lactose anhydrous, along with other excipients, in a direct compression process, results in a formulation with improved solubility, stability, and compressibility, achieving a desired dissolution profile and content uniformity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional fillers are used in avatrombopag maleate formulation, then manufacturing is simplified, but compressibility and stability deteriorate
Solution Approach 1:
The patent changes the physical and chemical parameters of the filler by selecting lactose anhydrous with specific crystal forms (monoclinic or triclinic) and controlling its moisture content to less than 5%. This parameter optimization resolves the contradiction by achieving both ease of manufacture through direct compression and improved stability in the final formulation.
Solution Approach 2:
The patent creates a composite formulation system combining avatrombopag maleate with lactose anhydrous as the primary filler, along with disintegrants and lubricants. This composite approach resolves the contradiction by synergistically combining materials that individually address compressibility, stability, and manufacturability requirements.
2Ease of manufacture
If lactose monohydrate is used as filler, then formulation is easier to prepare, but compressibility deteriorates
Solution Approach 1:
The patent resolves this contradiction by changing the hydration state parameter of lactose from monohydrate to anhydrous form, and optimizing the crystal structure to monoclinic or triclinic forms. This parameter change maintains ease of preparation while dramatically improving compressibility characteristics for direct compression manufacturing.
3Quantity of substance
If avatrombopag maleate is used in conventional formulations, then drug delivery is achieved, but solubility and dissolution profile deteriorate
Solution Approach 1:
The patent changes the dissolution parameters by optimizing the filler matrix composition and structure. Lactose anhydrous serves as a dissolution-enhancing filler that improves the dissolution profile of avatrombopag maleate through its specific crystal structure and interaction properties, thereby improving solubility while maintaining drug delivery effectiveness.
4Stability of the object's composition
If micronized active substance is used, then solubility is improved, but process complexity increases
Solution Approach 1:
The patent extracts the micronization step from the formulation process by using lactose anhydrous as a filler that provides dissolution enhancement without requiring the active substance to be micronized. This eliminates the complex micronization equipment and process steps while maintaining improved solubility and dissolution profile.
Data Source
AI summary
The present invention relates to a solid oral pharmaceutical formulation comprising avatrombopag maleate or a pharmaceutically acceptable salt, amorphous or crystalline form thereof and at least one filler, wherein the filler is lactose anhydrous. The present invention also relates to a simple, rapid, cost-effective, time-saving and industrially suitable process for preparing the solid oral pharmaceutical formulation.