Dry Tableting of TNO155 API for Crystal Stability
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Solution Overview
Problem
Existing methods for manufacturing tablets of the Active Pharmaceutical Ingredient (API) TNO155, such as wet granulation, face challenges including changes in the crystal form of the API, inferior tensile strength of tablets, and production of non-compacted powder.
Innovation Solution
The use of dry tableting methods like roller compaction and direct compression, which maintain the solid form status of TNO155 without converting its crystal form, and offer better densification, flow, and scalability compared to wet granulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If wet granulation is used to manufacture tablets of TNO155, then tablet formation is achieved, but the crystal form of the API changes and tensile strength becomes inferior
Solution Approach 1:
The patent changes the physical-chemical parameters of the granulation process by using dry granulation instead of wet granulation, specifically controlling moisture content and processing temperature to maintain the stable crystal form (Modification HA of succinate salt) of TNO155 while achieving adequate tablet tensile strength through optimized compression parameters
2Productivity
If wet granulation is used to manufacture tablets of TNO155, then tablet formation is achieved, but non-compacted powder is produced
Solution Approach 1:
The patent changes the moisture parameter from wet granulation to dry granulation conditions, eliminating the production of non-compacted powder while maintaining manufacturing efficiency through optimized dry processing parameters including compression force and granulation time
3Stability of the object's composition
If roller compaction is used instead of wet granulation, then crystal form stability is maintained and densification is improved, but process complexity increases
Solution Approach 1:
The patent extracts the harmful element of moisture from the granulation process by implementing dry granulation via roller compaction, thereby maintaining crystal form stability and improving densification while managing process complexity through streamlined equipment design and operation
Data Source
AI summary
The invention relates to a pharmaceutical formulation comprising the Active Pharmaceutical Ingredient (3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, where, in particular, the pharmaceutical formulation is made by a process comprising wet granulation, direct compression or especially roller compaction, and related invention aspects disclosed herein.