Large-Dose Boronophenylalanine Lyophilization Without Annealing
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Solution Overview
Problem
Existing methods for preparing large-specification dihydroxyboronphenylalanine lyophilized powder for injection face challenges such as high costs, long lyophilization times, and instability due to high solid content, making it difficult to achieve stable dosage forms and increasing sterility risks.
Innovation Solution
A preparation method involving pre-freezing, sublimation drying, and desorption drying with specific temperature and pressure conditions, eliminating the need for an annealing step, to produce a stable large-specification lyophilized powder.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If large-specification lyophilized formulations are prepared with high solid content, then the dosage form can be stabilized, but the lyophilization time increases and costs increase
Solution Approach 1:
The patent changes the lyophilization parameters by implementing a two-stage drying process with specific temperature profiles. The first stage uses -50°C to -20°C for pre-freezing, and the second stage uses -10°C to 0°C for sublimation drying, with controlled pressure conditions. This parameter optimization enables efficient lyophilization of large-specification formulations (3g-10g per vial) while maintaining dosage form stability and reducing lyophilization time compared to conventional single-stage methods.
Solution Approach 2:
The patent applies preliminary pre-freezing at -50°C to -20°C before the main sublimation drying process. This preliminary action ensures complete freezing of the solution, forming a stable ice crystal structure that supports the subsequent sublimation process. The pre-freezing step is crucial for large-specification formulations as it prevents collapse during drying and ensures proper dosage form formation, thereby enabling stable lyophilized products with reduced overall processing time.
2Stability of the object's composition
If large-specification lyophilized formulations are prepared with high solid content, then the dosage form can be stabilized, but the production cost increases
Solution Approach 1:
The patent optimizes lyophilization parameters including temperature (-50°C to 0°C), pressure (10-100 Pa), and drying time to achieve efficient water removal from large-specification formulations. By controlling these parameters, the process achieves complete drying and stable dosage form formation without requiring excessive energy input or extended processing times, thereby reducing production costs while maintaining product stability.
Solution Approach 2:
The preliminary pre-freezing step at -50°C to -20°C creates a stable ice crystal structure that facilitates efficient sublimation drying. This preliminary action reduces the energy required during the main drying phase and prevents product collapse, thereby reducing overall production costs while ensuring stable dosage form formation for large-specification formulations (3g-10g per vial).
3Quantity of substance
If multiple bottles are used for single injection, then the dosage requirement can be met, but the sterility risk increases and operation becomes cumbersome
Solution Approach 1:
The patent segments the lyophilized powder into single-use vials with optimized specifications (3g-10g per vial) that can be directly administered as single-dose formulations. This segmentation eliminates the need to open multiple bottles, thereby reducing sterility risks and simplifying the administration process while meeting the required dosage amounts for L-BPA therapy (100-500 mg/kg).
4Device complexity
If conventional lyophilization concentration and liquid volume are used, then the process is simple, but large-specification products cannot be prepared
Solution Approach 1:
The patent changes the lyophilization parameters by using lower temperatures (-50°C to 0°C), controlled pressure (10-100 Pa), and optimized drying time to enable preparation of large-specification formulations (3g-10g per vial). These parameter modifications allow the process to remain relatively simple while achieving the desired product specifications that were previously unattainable with conventional methods.
Solution Approach 2:
The preliminary pre-freezing step at -50°C to -20°C prepares the solution by forming a stable ice crystal structure, which facilitates the subsequent sublimation drying process. This preliminary action enables the lyophilization of large-specification formulations by preventing collapse during drying and ensuring proper dosage form formation, thereby expanding the achievable product specification range while maintaining process simplicity.
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 simplifies operation, reduces sterility risks, and lowers production costs while ensuring high dihydroxyboronphenylalanine content per vial, facilitating efficient and stable lyophilization.
Implementation Method 1
lyophilization includes pre-freezing, sublimation drying, and desorption drying
Implementation Method 2
lyophilization includes pre-freezing, sublimation drying, and desorption drying
Data Source
Figure 1~4
AI summary
The present invention relates to the technical field of medicine and provides a preparation method for large-specification dihydroxyboronphenylalanine lyophilized powder for injection. The preparation method for large-specification dihydroxyboronphenylalanine lyophilized powder for injection includes: mixing dihydroxyboronphenylalanine, a polyol, a base, and part of a solvent to obtain a first mixed solution; adjusting the pH of the first mixed solution by using a pH regulator, and adding the remaining part of the solvent to obtain a second mixed solution, wherein the concentration of dihydroxyboronphenylalanine in the second mixed solution is 160-250 mg/mL; and aliquoting the second mixed solution, followed by lyophilization, where the lyophilization includes pre-freezing, sublimation drying, and desorption drying. By the preparation method of the present invention, stable large-specification dihydroxyboronphenylalanine lyophilized powder for injection can be prepared. The method of the present invention has the characteristics of stable process and reasonable lyophilization time, thereby greatly reducing the lyophilization costs.