Aprocitentan Solid-State Forms for Stability and Dissolution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for additional solid state forms of Aprocitentan, including crystalline polymorphs and salts, to improve processing, handling, stability, and bioavailability for the treatment of hypertension.
Innovation Solution
The development of crystalline polymorphs of Aprocitentan, Aprocitentan:piperazine, Aprocitentan:methanesulfonic acid, and Aprocitentan:ethanesulfonic acid, along with processes for their preparation and pharmaceutical compositions, to enhance properties such as chemical stability, dissolution profile, and shelf-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If additional solid state forms and salts of Aprocitentan are developed, then processing characteristics, stability, and bioavailability are improved, but device complexity and formulation complexity increase
Solution Approach 1:
The patent applies parameter changes by developing multiple solid state forms (polymorphs, salts, co-crystals) of Aprocitentan with different physical and chemical properties. Each form represents a change in the physical state parameters of the compound, allowing optimization of stability, processing characteristics, and bioavailability while managing formulation complexity through systematic exploration of solid state chemistry
Solution Approach 2:
The patent employs composite materials by creating co-crystal forms of Aprocitentan combined with different counterions and coformers. These composite solid state structures integrate multiple molecular components into new crystalline assemblies, enabling simultaneous improvement of stability and processing properties while providing distinct physical characteristics for formulation development
2Productivity
If multiple crystalline forms and salts are prepared, then bioavailability and dissolution profile are enhanced, but manufacturing precision and process complexity increase
Solution Approach 1:
The patent utilizes phase transitions in the development of different crystalline forms and salts of Aprocitentan. By controlling phase changes during crystallization processes, the patent achieves distinct solid state forms with optimized dissolution profiles and bioavailability. The phase transition approaches enable systematic variation of physical properties while maintaining process control through defined crystallization conditions
3Ease of operation
If new solid state forms are discovered and developed, then processing and handling characteristics are improved, but loss of time for characterization and validation increases
Solution Approach 1:
The patent applies preliminary action by systematically preparing and characterizing multiple solid state forms, salts, and co-crystals before final formulation selection. This preliminary exploration of solid state chemistry enables identification of optimal forms with improved processing characteristics early in the development process, reducing later validation time and enabling more efficient formulation development
Data Source
AI summary
The present disclosure encompasses novel solid state forms of Aprocitentan, Aprocitentan salts and Aprocitentan co-crystals, processes for preparation thereof, and pharmaceutical compositions thereof.