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 are complex, often deactivating the drugs and resulting in low encapsulation rates and unsatisfactory release profiles due to issues like particle size limitations, solvent volatility, and additive interference.
Innovation Solution
A method involving the preparation of a solid dispersion of a water-soluble drug and a biodegradable polymer, followed by emulsification in a surfactant-containing aqueous phase and solvent volatilization to form microparticles without pre-preparing small drug powders, maintaining bioactivity and achieving high encapsulation and sustained release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional microparticle preparation methods (solvent evaporation, coacervation, spray drying) are used, then sustained-release microparticles can be formed, but the process becomes complex and drug bioactivity is lost due to harsh conditions
Solution Approach 1:
The invention changes the key parameter of preparation temperature from conventional high-temperature processes to low-temperature (0-4°C) conditions, thereby preserving drug bioactivity while simplifying the overall process. The solid dispersion technique allows drug-polymer mixing at low temperatures, and the emulsion-solvent volatilization proceeds at refrigeration temperatures, eliminating the need for complex high-temperature control systems.
Solution Approach 2:
The invention extracts and eliminates the problematic high-temperature step from the conventional preparation process. By using solid dispersion at low temperatures and refrigerated solvent volatilization, the harmful thermal effects are removed while retaining the essential microparticle formation function.
2Ease of manufacture
If large particle size drug powder (10-1000 μm) is used directly in S/O/W double emulsion method, then the process is simple, but encapsulation rate decreases and sustained-release effect is unsatisfactory
Solution Approach 1:
The invention performs preliminary action by pre-forming solid dispersion of the drug in the polymer matrix before emulsification. This solid dispersion step pre-distributes the drug at the molecular or micro-level within the polymer, ensuring uniform encapsulation without requiring subsequent particle size reduction, thus maintaining process simplicity while achieving high encapsulation rates.
Solution Approach 2:
The solid dispersion acts as an intermediary form between the original drug powder and the final microparticles. It provides a pre-mixed drug-polymer composite that emulsifies uniformly, bridging the gap between simple processing and high encapsulation efficiency.
3Manufacturing precision
If drug powder is ground or pulverized to reduce particle size to 1-10 μm, then encapsulation rate improves, but the process becomes complex and drug may be deactivated
Solution Approach 1:
The invention extracts and eliminates the particle size reduction step (grinding, pulverization) from the conventional process. By using solid dispersion, the drug is mixed with polymer at low temperatures in its original particle form, and the emulsification process naturally produces uniformly sized microparticles with high encapsulation efficiency, removing the need for complex size reduction equipment and procedures.
Solution Approach 2:
The invention changes the approach from mechanical size reduction to thermal parameter control. By maintaining low temperatures throughout the process and using solid dispersion followed by emulsification, the system achieves fine microparticle formation without mechanical grinding, thereby avoiding deactivation and process complexity.
4Reliability
If frequent high-dose injections are administered to maintain therapeutic concentration, then desired therapeutic effect is achieved, but systemic toxicity increases and patient compliance decreases
Solution Approach 1:
The invention creates a dynamic sustained-release system where the microparticles gradually release the drug over time as the polymer matrix degrades. This transforms the static high-dose injection approach into a dynamic controlled-release system, maintaining therapeutic concentrations continuously while avoiding peak-dose toxicity and reducing administration frequency.
Solution Approach 2:
The drug is pre-encapsulated in the polymer matrix in a sustained-release formulation, creating a reservoir that releases the drug gradually. This preliminary encapsulation action eliminates the need for repeated high-dose injections, as the single administration provides continuous therapeutic effect over weeks or months.
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
This method simplifies the process, maintains drug bioactivity, and achieves excellent sustained-release effects with high encapsulation rates and controlled drug delivery for several weeks or months, overcoming previous issues of burst release and incomplete release.
Implementation Method 1
dissolving the solid dispersion prepared in step 1) in an organic solvent C to form a solid dispersion emulsion (internal oil phase), the organic solvent C being an organic solvent which is not capable of dissolving the water-soluble drug but capable of dissolving the poorly water-soluble polymer
Implementation Method 2
solidifying microparticles in the emulsion by solvent volatilization or solvent extraction
Implementation Method 3
solidifying microparticles in the emulsion by solvent volatilization or solvent extraction
Data Source
Figure 1
AI summary
The present invention provides sustained-release microparticles. 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.