API Crystal Form Particle Size Control for Dissolution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for diseases caused by coronaviruses, particularly 2019-nCoV, lack effective pharmaceutical compositions that can meet the urgent clinical needs during public health emergencies like the COVID-19 pandemic.
Innovation Solution
A pharmaceutical composition containing a crystal form of a compound of Formula (I) and fumaric acid, characterized by specific X-ray powder diffraction peaks and particle sizes, is developed. This composition includes the active pharmaceutical ingredient and physiologically acceptable excipients like fillers, disintegrants, lubricants, and binders, enabling rapid and uniform dispersion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional pharmaceutical compositions are used for coronavirus treatment, then the treatment can be provided, but the dissolution rate and clinical effectiveness are insufficient
Solution Approach 1:
The patent applies parameter changes by controlling the particle size of the active pharmaceutical ingredient to specific ranges (D90: 10-30 μm, D50: 5-15 μm) and establishing specific crystal form characteristics with defined X-ray diffraction peaks. These parameter optimizations enhance the dissolution rate while maintaining clinical effectiveness, directly resolving the contradiction between productivity and reliability in coronavirus treatment.
2Productivity
If the particle size of the active pharmaceutical ingredient is reduced to improve dissolution, then the dissolution rate increases, but the manufacturing precision requirements increase
Solution Approach 1:
The patent specifies precise particle size parameters (D90: 10-30 μm, D50: 5-15 μm) that balance dissolution enhancement with manufacturing feasibility. By defining clear parameter ranges rather than requiring ultra-fine particles, the patent achieves improved dissolution rate while maintaining reasonable manufacturing precision requirements.
Solution Approach 2:
The patent employs crystal form control and molecular-level structure optimization (through specific crystal packing and intermolecular forces) to enhance dissolution properties, replacing purely mechanical particle size reduction approaches with a combination of crystalline structure engineering and controlled particle sizing.
3Reliability
If crystal form with specific X-ray peaks is developed to improve stability, then the stability increases, but the development complexity increases
Solution Approach 1:
The patent identifies and controls specific crystal form parameters through characteristic X-ray diffraction peaks (e.g., 2θ values of 10.94°, 19.06°, 23.50°, 24.66°). By focusing on these specific crystalline parameters rather than attempting to control every molecular interaction, the patent achieves enhanced stability with manageable development complexity.
Data Source
AI summary
The present disclosure provides an active pharmaceutical ingredient containing a crystal form including a compound of Formula (I) and fumaric acid. An X-ray powder diffraction pattern of the crystal form obtained by using Cu-Kα radiation includes at least three peaks selected from the group consisting of 10.94°±0.2° 2θ, 19.06°±0.2° 2θ, 23.50°±0.2° 2θ, and 24.66°±0.2° 2θ; a particle size D90 of the active pharmaceutical ingredient is smaller than or equal to 20 μm, and a particle size D50 of the active pharmaceutical ingredient is smaller than or equal to 10 μm.