Polymer Microparticle Preparation via Solvent Diffusion
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Solution Overview
Problem
Current processes for producing pharmaceutical formulations for long-acting injections are complex, limited by drug load, and often result in non-optimal release profiles and side effects, particularly for antipsychotic medications.
Innovation Solution
A process for producing nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell, using polylactide, polyglycolide, and polyester copolymers, with benzyl alcohol as a solvent, allowing for high drug load and controlled release, and avoiding halogenated solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If complex processes are used to manufacture microspheres for long-acting injections, then controlled release can be achieved, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent changes the chemical parameters of the polymer matrix by using specific copolymer compositions (e.g., PLGA with defined lactic acid to glycolic acid ratios) and controlling polymer molecular weight and crystallinity. These parameter changes enable controlled release without complex manufacturing processes, as the release characteristics are inherently determined by the polymer's chemical structure and degradation kinetics.
Solution Approach 2:
The patent employs composite polymer materials, specifically copolymers combining lactic acid and glycolic acid units, to create microparticles with tailored release profiles. The composite nature of these polymers allows for optimized degradation rates and mechanical properties, achieving controlled release through material composition rather than complex processing.
2Productivity
If high drug load is achieved, then productivity and therapeutic efficacy improve, but manufacturing precision and encapsulation efficiency become more difficult to control
Solution Approach 1:
The patent optimizes the polymer to drug ratio and controls polymer crystallinity parameters to achieve high drug loading while maintaining precision. By adjusting the polymer's physical state and crystalline structure, the process ensures uniform drug distribution and consistent encapsulation efficiency even at high drug loads, preventing aggregation and ensuring homogeneous release.
3Stability of the object's composition
If esterification with fatty acid is used to improve solubility and avoid first pass effect, then pharmacokinetic stability improves, but harmful side effects increase
Solution Approach 1:
The patent extracts and eliminates the harmful esterification step from the formulation process. Instead of using fatty acid esters that cause local tissue reactions and pain, the invention directly incorporates the active pharmaceutical ingredient into polymer microparticles. This extraction of the problematic chemical modification maintains plasma stability through polymer-controlled release while avoiding the harmful side effects of ester-based formulations.
Solution Approach 2:
The patent converts the need for enhanced solubility and stability (which previously required harmful esterification) into a beneficial polymer-based delivery system. The polymer matrix provides the necessary stability and controlled release without requiring chemical modification of the drug, thereby converting a harmful approach into a safe and effective one.
4Ease of manufacture
If conventional solvent systems are used in microparticle formation, then manufacturing ease improves, but harmful environmental and health effects increase
Solution Approach 1:
The patent changes the chemical composition parameters of the solvent system by eliminating halogenated solvents and using alternative non-halogenated solvents or solvent-free approaches. This parameter change maintains the ease of manufacture through standard microparticle formation techniques while removing harmful substances from the process, achieving both manufacturing simplicity and environmental/health safety.
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 process achieves high encapsulation efficiency and controlled release of active agents, reducing side effects and improving medication adherence for chronic conditions like mental disorders, with scalable and efficient production.
Implementation Method 1
nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell
Implementation Method 2
allowing the spontaneous formation of a suspension of the nano- and/or microparticles via transfer of organic solvent from the discontinuous organic phase into the continuous aqueous phase
Data Source
AI summary
Provided is a process for the production of nano- and/or microparticles containing a therapeutically active agent embedded in a polymer matrix or encapsulated by a polymer shell, and nano- and/or microparticles obtainable by the process, said process comprising the steps of:a) providing a solution of a polymer selected from polylactide, polyglycolide, and polyester copolymers comprising copolymerized units of lactic acid and/or glycolic acid in an organic solvent S1 having limited water solubility;b) providing a solution or dispersion of a therapeutically active agent in as solvent or mixture of organic solvents S2 comprising at least 50 vol. % benzyl alcohol,c) combining the solution or the solution and suspension provided in step a) and step b) to provide an organic phase which comprises dissolved polymer and dissolved therapeutically active agent in a mixture of the organic solvents S1 and S2;d) agitating the organic phase provided in step c) in a vessel and adding an aqueous surfactant solution to the agitated organic phase in a volume ratio of at least 2:1 in terms of the total volume of the aqueous surfactant solution to the total volume of the organic phase as provided in step c), thus causing the formation of a dispersion containing a continuous aqueous phase and a discontinuous organic phase; ande) allowing the spontaneous formation of the nano- and/or microparticles via transfer of organic solvent from the discontinuous organic phase into the continuous aqueous phase directly after the dispersion has been formed.