Multi-branched Copolymer In Situ Forming Depot Injectability
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Solution Overview
Problem
Current solvent-exchange in situ forming depot (ISFD) technologies face challenges with high viscosity, injectability, and slow degradation kinetics, limiting their effectiveness for sustained release of pharmaceutical active ingredients.
Innovation Solution
A pharmaceutical composition comprising a multi-branched copolymer with at least three poly(ε-caprolactone-co-lactic acid) arms attached to a central polyether core, combined with a pharmaceutically acceptable organic solvent, which forms an insoluble depot in aqueous solutions, enhancing injectability and modulating the release profile of active ingredients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If linear PEG-polyester copolymers are used for solvent-exchange in situ forming depot, then sustained release capability is achieved, but viscosity becomes high and injectability deteriorates
Solution Approach 1:
The linear copolymer chain is segmented into multiple branches radiating from a central core, creating a star-shaped architecture. This segmentation reduces chain entanglement and intermolecular interactions, thereby lowering viscosity while maintaining the sustained release capability through the same solvent-exchange mechanism.
Solution Approach 2:
The polymer architecture transitions from one-dimensional linear chains to a multi-dimensional star-shaped structure with multiple arms radiating from a central core. This dimensional change reduces the hydrodynamic volume and chain entanglement, improving injectability while preserving the depot-forming functionality.
2Duration of action of stationary object
If linear PEG-polyester copolymers are used for solvent-exchange in situ forming depot, then sustained release capability is achieved, but degradation kinetics become slow
Solution Approach 1:
The polyester segments are divided into multiple separate arms rather than one continuous linear chain. This segmentation increases the surface area-to-volume ratio and exposes more ester bonds to water, accelerating hydrolysis and degradation kinetics while still providing sustained release through the depot mechanism.
Solution Approach 2:
The molecular architecture parameter is changed from linear to star-shaped, which alters the degradation behavior. The star-shaped structure provides more accessible ester linkages to water molecules, increasing the degradation rate constant while maintaining the controlled release profile.
3Ease of operation
If multi-branched copolymer with polyether core and polyester arms is used, then viscosity is reduced and injectability is improved, but polymer structure complexity increases
Solution Approach 1:
The polymer is designed as a composite structure combining a polyether core with polyester arms, integrating the beneficial properties of both polymer types. The polyether core provides water solubility and processability, while the polyester arms provide biodegradability and controlled release, achieving improved injectability without excessive complexity.
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 composition achieves lower viscosity, improved injectability, and sustained release of pharmaceutical active ingredients, providing a bioresorbable depot with controlled release kinetics, suitable for prolonged delivery of drugs up to several months.
Implementation Method 1
WO2012/090070A describes a solvent-exchange in situ forming depot (ISFD) technology comprising a mixture of linear (m)PEG-polyester dissolved in a biocompatible organic solvent. Upon injection, the solvent diffuses and the polymers, insoluble in water, precipitate and form a depot
Implementation Method 2
Upon injection, the solvent diffuses and the polymers, insoluble in water, precipitate and form a depot that can entrap an active pharmaceutical ingredient (API)
Implementation Method 3
Upon injection, the solvent diffuses and the polymers, insoluble in water, precipitate and form a depot
Data Source
AI summary
The present invention provides a pharmaceutical composition comprising:a multi-branched copolymer comprising at least three polyester arms, wherein the polyester is poly(ε-caprolactone-co-lactic acid), attached to a central core which comprises a polyether, and wherein the multi-branched copolymer is substantially insoluble in aqueous solution, further comprising at least one pharmaceutically active ingredient, and a pharmaceutically acceptable organic solvent in an amount of at least 20% (w/w %) of the total composition.