Protein Microparticles Stabilizer Ratio for Ambient Stability
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Solution Overview
Problem
Current therapeutic protein formulations face challenges in maintaining stability and high concentration at ambient temperatures, leading to degradation and aggregation, which complicates storage and delivery, especially in areas without reliable refrigeration.
Innovation Solution
A method of formulating pharmaceutical powders by atomizing an aqueous solution containing a glycoprotein and thermal stabilizer, followed by evaporation to create protein powders with a high glycoprotein content and biodegradable polymer coating, optimizing the protein to stabilizer ratio to enhance stability and concentration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the concentration of therapeutic protein is increased to maximize drug delivery, then the amount of protein per unit volume is maximized, but the protein becomes destabilized and prone to degradation and aggregation
Solution Approach 1:
The patent changes the physical state of the protein from liquid solution to solid powder formulation, and adjusts the ratio of stabilizer to protein to specific ranges (molar ratio of 50:1 to 200:1, or weight ratio of 1:5 to 2:5). This parameter optimization allows high protein concentration (up to 97% w/w) while maintaining stability at ambient temperature, resolving the contradiction between maximizing concentration and maintaining protein stability
Solution Approach 2:
The patent creates a composite powder formulation combining therapeutic protein with specific stabilizing excipients (such as sugars, amino acids, or polymers) in optimized ratios. This composite structure provides both high protein content and enhanced stability, allowing the formulation to remain stable at ambient temperature while delivering high concentrations of active protein
2Stability of the object's composition
If stabilizer concentration is increased to maintain protein stability, then protein degradation and aggregation are reduced, but the total protein concentration that can be accommodated is reduced
Solution Approach 1:
The patent optimizes the stabilizer-to-protein ratio to specific ranges (molar ratio of 50:1 to 200:1, or weight ratio of 1:5 to 2:5), which is more efficient than conventional formulations. This optimized parameter range allows sufficient stabilization with minimal stabilizer, thereby maximizing the amount of protein that can be accommodated in the formulation
3Ease of operation
If liquid formulation is used to provide convenient administration, then ease of administration is improved, but long term stability at ambient temperature is lost
Solution Approach 1:
The patent transitions the protein formulation from liquid phase to solid powder phase through spray-drying or lyophilization. This phase change enables the formulation to achieve long-term stability at ambient temperature while maintaining the ability to be reconstituted to liquid form for administration, thus resolving the contradiction between ease of administration and ambient temperature stability
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 stable and high-concentration protein formulations that remain biologically active at ambient temperatures, reducing degradation and aggregation, thus improving storage and delivery efficiency.
Implementation Method 1
an aqueous solution containing a thermal stabilizer and a glycoprotein with a mass ratio at or between 1:5-2:5 is atomized
Implementation Method 2
Heat is then applied to the atomized aqueous solution to evaporate the water from the aerosolized droplets and form a protein powder
Data Source
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AI summary
Micron-sized particles containing a therapeutic protein and optionally excipients and a coating of a biocompatible and biodegradable polymer, and methods of making and using those microparticles are pfrovided. The therapeutic protein formulated as a pharmaceutical powder of micron-sized particles remains stable for extended periods of time and is amenable to polymer coating for extended release and stability under physiological conditions.