Crystalline Bis-Choline Tetrathiomolybdate Particles for Stable Dosage Forms
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Bis-choline tetrathiomolybdate (BC-TTM) degrades easily under storage and tableting conditions, leading to impurity formation in solid unit dosage forms, making it challenging to create a stable pharmaceutical form for treating Wilson Disease and other conditions.
Innovation Solution
Development of novel crystalline particles of BC-TTM with specific particle size distributions and low impurity levels, achieved through controlled heating, solvent addition, and drying processes, resulting in stable solid unit dosage forms such as tablets and capsules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If BC-TTM is formulated as a solid unit dosage form, then it enables convenient administration for treating Wilson Disease, but it degrades under storage and tableting conditions leading to impurity formation
Solution Approach 1:
The patent changes the physical and chemical parameters of BC-TTM by establishing specific particle size distributions (D10, D50, D90 values) and crystal morphology characteristics. These parameter changes result in a stable crystalline form that resists degradation during storage and tableting while maintaining pharmaceutical usability
Solution Approach 2:
The patent creates a composite crystalline structure with specific morphological characteristics and size distribution profile. This composite approach combines multiple structural features (crystal habit, particle size range, surface area characteristics) to achieve both stability and functionality
2Ease of manufacture
If BC-TTM is processed through tableting, then it produces a solid unit dosage form, but it causes degradation and impurity formation
Solution Approach 1:
The patent performs preliminary crystallization under controlled conditions to establish the desired particle size distribution and crystal morphology before tableting. This preliminary action ensures the material is pre-configured in a stable form that withstands subsequent manufacturing processes without degrading
Solution Approach 2:
The patent modifies key parameters including particle size distribution (D50, D90 values) and crystal habit to create a form that is both manufacturable and stable. These parameter changes enable successful tableting while preventing impurity formation
3Duration of action of stationary object
If BC-TTM is stored over time, then it maintains availability for use, but it degrades and forms impurities
Solution Approach 1:
The patent establishes specific particle size parameters (D10, D50, D90) and surface area characteristics that optimize storage stability. These parameter changes create a crystalline form with reduced surface energy and improved chemical stability during long-term storage
Solution Approach 2:
The patent creates a stable crystalline structure with specific morphological characteristics that acts as a protective framework, cushioning the BC-TTM molecules against degradation pathways during storage. This pre-established structural stability prevents impurity formation over time
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method produces stable BC-TTM formulations with reduced impurities, enhancing storage stability and efficacy for treating Wilson Disease and other copper accumulation disorders.
Implementation Method 1
heating the solution of BC-TTM to a first temperature between about 35° C. and 50° C.
Implementation Method 2
gradually adding ethanol or isopropanol to the solution of BC-TTM over a time period of at least one hour; cooling the solution of BC-TTM to a second temperature between about 10° C. and 25° C. to produce solid BC-TTM
Implementation Method 3
cooling the solution of BC-TTM to a second temperature between about 10° C. and 25° C. to produce solid BC-TTM
Implementation Method 4
drying the solid BC-TMM at a third temperature between about 20° C. and 30° C. under reduced pressure
Data Source
AI summary
Novel crystalline particles, methods for manufacture of crystalline particles, and solid unit dosage forms, particularly tablets or capsules, of bis-choline tetrathiomolybdate are provided. In particular, provided herein are crystalline particles that allow for a more stable solid unit dosage form of bis-choline tetrathiomolybdate.