Lurasidone Suspension Particle Control via Recrystallization
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Solution Overview
Problem
Current long-acting lurasidone injection preparations face challenges in controlling particle size distribution, leading to inconsistent sustained-release periods and potential patient non-compliance due to complex preparation processes and early release profiles.
Innovation Solution
A method for preparing lurasidone that controls temperature and dispersion conditions during recrystallization to achieve a consistent irregular particle form, resulting in rapid initial drug concentration increase followed by sustained release, with a preparation process involving dissolving lurasidone in an organic solvent, cooling, and controlling stirring or shearing speeds to achieve desired particle sizes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If wet medium grinding method is used to prepare lurasidone nanosuspension, then particle size can be controlled, but the sustained-release period is only 3-7 days and production complexity increases due to cleaning and sterilization requirements
Solution Approach 1:
The patent changes the preparation method from wet medium grinding to a new crystallization process with controlled temperature and dispersion conditions. This parameter change enables both extended sustained-release period (30-90 days) and consistent particle size control, resolving the contradiction between manufacturing precision and duration of action
Solution Approach 2:
The patent utilizes controlled crystallization phase transition during the preparation process. By controlling temperature and dispersion conditions during crystallization, the patent achieves consistent irregular particle formation that provides both manufacturable precision and extended sustained-release duration without the limitations of wet grinding methods
2Duration of action of moving object
If back-dropping method is used to prepare lurasidone sustained-release preparation, then sustained-release effect can be achieved, but particle size distribution control becomes complex requiring multiple parameter systems and additional bypass cycles
Solution Approach 1:
The patent simplifies the complex parameter system of back-dropping method by implementing a new crystallization process with controlled temperature and dispersion conditions. This reduces the number of parameters to control while maintaining sustained-release effect, directly addressing the device complexity issue
Solution Approach 2:
The patent extracts and eliminates the complex parameter control requirements (stirring speed, crystallization temperature, organic phase/aqueous solution volume ratio, dropping rate) from the preparation process. The new method achieves particle size distribution control with fewer parameters, removing the need for additional bypass cycles and reducing overall process complexity
3Manufacturing precision
If conventional crystallization methods are used, then particle size can be controlled, but particle form consistency is poor leading to inconsistent sustained-release periods
Solution Approach 1:
The patent implements specific temperature control and dispersion condition parameters during crystallization that consistently produce irregular particle form. This parameter optimization ensures both particle size control and particle form consistency, leading to stable sustained-release periods of 30-90 days
Solution Approach 2:
The patent creates specific local conditions during crystallization (controlled temperature and dispersion) that promote consistent irregular particle formation. This local quality control ensures uniform particle characteristics throughout the batch, improving both manufacturing precision and composition stability
4Speed
If early release profile is used in long-acting injection, then rapid drug concentration increase is achieved, but sustained-release consistency becomes problematic and requires additional oral tablets
Solution Approach 1:
The patent optimizes crystallization parameters (temperature and dispersion conditions) to create particles with consistent irregular forms that provide balanced release profiles. This enables both rapid initial drug concentration increase and consistent sustained-release over 30-90 days, eliminating the need for additional oral tablets
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 achieves a sustained-release effect of at least 30 days without the need for additional oral tablets, improving patient compliance and stability of the pharmaceutical composition.
Implementation Method 1
dissolving lurasidone in an organic solvent under heating to obtain a solution of lurasidone
Implementation Method 2
cooling the solution obtained in step (1) to room temperature (e.g., 25° C.) to precipitate crystals
Implementation Method 3
cooling the solution obtained in step (1) to room temperature (e.g., 25° C.) to precipitate crystals
Implementation Method 4
controlling stirring speed to 100 rpm to 2000 rpm, and/or shear line speed to 1 m/s to 32 m/s
Data Source
AI summary
The present disclosure relates to an injectable lurasidone suspension and a preparation method thereof, and in particular to an irregular form of a lurasidone solid and a pharmaceutical composition thereof. The present disclosure also relates to a preparation method for the solid and the pharmaceutical composition thereof, and an application thereof in the treatment of mental diseases. According to the present disclosure, the lurasidone solid prepared has controllable particle size and has Dv5O particle size of 6 μm to 110 μm. The good particle size stability can also he maintained in the pharmaceutical composition. The lurasidone suspension preparation obtained by the method is fast-acting, has a long sustained release period, and can effectively reduce the risk caused by poor patient compliance.