Sustained-Release Microparticles via Low-Temperature Solid Dispersion
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Solution Overview
Problem
Current methods for preparing sustained-release microparticles of water-soluble drugs like proteins and peptides face challenges such as low bioavailability, poor stability, and inefficient release profiles due to complex preparation processes and the use of surfactants, which can denature proteins and affect encapsulation rates.
Innovation Solution
A method involving the preparation of a solid dispersion of a water-soluble drug and a biodegradable polymer, followed by emulsification in an organic solvent and subsequent solvent volatilization to form microparticles without pre-grinding the drug, maintaining bioactivity and achieving high encapsulation and sustained release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If the average particle size of drug powder is reduced to 1-10 μm to achieve high encapsulation rate and satisfactory sustained-release effect, then the encapsulation rate is improved and sustained-release effect is enhanced, but the preparation process becomes more complex and requires additional particle size reduction steps
Solution Approach 1:
The patent applies preliminary action by pre-grinding the water-soluble drug into fine powder with controlled particle size (1-10 μm) before emulsification. This preliminary particle size reduction ensures that the drug can be effectively encapsulated in the polymer matrix during the subsequent S/O/W double emulsion process, achieving high encapsulation rates and satisfactory sustained-release effects without requiring complex in-process size control mechanisms.
Solution Approach 2:
The patent replaces complex mechanical size control systems with a simpler approach by using pre-grinding followed by direct emulsification. Instead of employing sophisticated in-process particle size control mechanisms, the method substitutes a straightforward mechanical grinding step performed beforehand, simplifying the overall device complexity while maintaining manufacturing precision.
2Device complexity
If conventional S/O/W double emulsion method is used with pre-prepared protein powder of large particle size (10-1000 μm), then the preparation process is simpler, but the encapsulation rate is low and sustained-release effect is insufficient
Solution Approach 1:
The patent applies preliminary action by pre-grinding the water-soluble drug into fine powder with controlled particle size (1-10 μm) before emulsification. This preliminary particle size reduction ensures that the drug can be effectively encapsulated in the polymer matrix during the subsequent S/O/W double emulsion process, achieving high encapsulation rates and satisfactory sustained-release effects without requiring complex in-process size control mechanisms.
3Manufacturing precision
If drug powder is pre-grinded to small particle size to achieve high encapsulation rate, then the encapsulation rate is improved, but the drug may be deactivated during the grinding process
Solution Approach 1:
The patent applies parameter changes by carefully controlling the particle size reduction process parameters to achieve the optimal balance between particle size and drug stability. By specifying a particle size range of 1-10 μm and controlling the grinding conditions, the method ensures sufficient size reduction for high encapsulation while minimizing mechanical stress and heat generation that could deactivate the drug, thus maintaining drug bioactivity.
4Quantity of substance
If injection administration is used to achieve high systemic concentration for desired therapeutic effect, then the therapeutic effect is achieved, but patient compliance is low due to pain and frequent injections
Solution Approach 1:
The patent applies preliminary action by pre-encapsulating the water-soluble drug in biodegradable polymer microparticles with controlled release properties. This preliminary encapsulation creates a sustained-release system that maintains therapeutic concentrations over extended periods, eliminating the need for frequent injections and thereby improving patient compliance while maintaining the required systemic concentration for therapeutic effect.
Solution Approach 2:
The patent applies continuity of useful action through the sustained-release mechanism of the polymer-encapsulated drug system. The biodegradable polymer matrix continuously releases the drug over an extended period, maintaining therapeutic concentrations without interruption. This continuous release action replaces the discontinuous dosing required by conventional injections, thereby improving patient compliance while achieving the desired therapeutic effect.
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 results in microparticles with improved bioavailability, stability, and sustained release profiles, overcoming the limitations of traditional methods by ensuring zero-order release and extended drug delivery for several weeks or months.
Implementation Method 1
dissolving the solid dispersion in an organic solvent to form an internal oil phase
Implementation Method 2
adding the internal oil phase into an external aqueous phase to form an emulsion
Implementation Method 3
removing the organic solvent by volatilization or extraction to solidify the microparticles
Data Source
AI summary
In the present invention, the whole preparation process of the sustained-release microparticles is at normal or low temperature, which is highly advantageous for the preparation of a polymer-based composition from a high-temperature-sensitive drug, particularly a protein, nucleic acid and peptide drug, and the bioactivity of the active substance can be maintained to the greatest extent throughout the process compared to the disclosed technology; at the same time, the prepared sustained-release microparticles have an excellent sustained-release effect close to zero order, and the drug concentration is stabilized during the release, which overcomes the defects that the microparticles obtained by the conventional S/O/W process of pre-preparing the drug microparticles have no drug release in the earlier stage and a rapid release of the drug in the later stage; and in addition, the sustained-release microparticles have higher drug loading rate and drug encapsulation rate.