Dihydroxyboronphenylalanine Lyophilized Powder with Faster High-Solid Drying
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Solution Overview
Problem
Existing methods for preparing large-specification dihydroxyboronphenylalanine lyophilized powder for injection face challenges such as high production costs, long lyophilization times, and instability due to high solid content, making it difficult to achieve stable dosage forms suitable for clinical use.
Innovation Solution
A preparation method involving pre-freezing, sublimation drying, and desorption drying with controlled temperature and pressure conditions, eliminating the need for an annealing step, to produce stable large-specification lyophilized powder.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If large-specification lyophilized formulations are prepared with high solid content, then the dosage form can provide high dihydroxyboronphenylalanine content per vial, but the water sublimation is hindered leading to long lyophilization time and high production costs
Solution Approach 1:
The patent changes the lyophilization parameters by conducting primary drying at elevated temperatures (−10°C to 2°C) compared to conventional lower temperatures, while maintaining vacuum conditions. This parameter change enables faster water sublimation from high solid content formulations without compromising product stability, thereby reducing lyophilization time while maintaining high dihydroxyboronphenylalanine content per vial
Solution Approach 2:
The patent implements a two-stage drying process with periodic action: first primary drying at elevated temperature to remove bulk water, then secondary drying at lower temperature to remove residual water. This periodic action allows efficient water removal from high solid content formulations while managing thermal stress, reducing overall lyophilization time while maintaining product quality
2Quantity of substance
If large-specification lyophilized formulations are prepared with high solid content, then the dosage form can provide high dihydroxyboronphenylalanine content per vial, but the production cost increases due to extended lyophilization process
Solution Approach 1:
The patent changes the lyophilization temperature parameter to elevated ranges (−10°C to 2°C) during primary drying, which significantly accelerates water sublimation rates. This parameter change reduces the total lyophilization time and energy consumption, thereby lowering production costs while maintaining high dihydroxyboronphenylalanine content per vial through optimized process parameters
3Device complexity
If conventional lyophilization concentration and liquid volume are used, then the process is simple, but multiple bottles are needed for single injection increasing operation complexity and sterility risk
Solution Approach 1:
The patent segments the lyophilized powder into single-dose vials containing 3-7.5g dihydroxyboronphenylalanine, where each vial is designed for single use. This segmentation eliminates the need for multiple bottles and manual dissolving operations, simplifying the injection process while maintaining sterility through single-use packaging design
4Quantity of substance
If large-specification lyophilized formulations are prepared, then high dihydroxyboronphenylalanine content per vial is achieved, but the product may collapse when melting due to temperature rise or ice crystal support structure removal
Solution Approach 1:
The patent changes the lyophilization temperature parameter to elevated ranges (−10°C to 2°C) during primary drying, which promotes formation of a stable amorphous glassy matrix structure. This parameter change prevents collapse of the dosage form when melting by creating a more robust molecular structure that resists structural degradation during subsequent warming and ice crystal removal phases
Solution Approach 2:
The patent creates a composite structure during lyophilization where dihydroxyboronphenylalanine molecules are embedded in an amorphous glassy matrix formed by the freezing and rapid drying of the solution. This composite material structure provides mechanical stability and prevents collapse when the product is warmed or the ice crystal support structure is removed, while maintaining high dihydroxyboronphenylalanine content
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 lyophilized powder production.
Implementation Method 1
lyophilization includes pre-freezing, sublimation drying, and desorption drying
Implementation Method 2
lyophilization includes pre-freezing, sublimation drying, and desorption drying
Implementation Method 3
lyophilization includes pre-freezing, sublimation drying, and desorption drying
Data Source
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.