Polymerized Nanocapsules for Bendamustine Stability
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Solution Overview
Problem
Bendamustine hydrochloride is unstable in aqueous solutions, leading to technical difficulties in its preparation and administration, and its short half-life limits its suitability for treating certain types of solid tumors, restricting the expansion of its therapeutic use.
Innovation Solution
The method involves forming an emulsion with a continuous organic solvent phase and a dispersed aqueous phase containing a pharmaceutically acceptable salt of bendamustine, treating it with a base to convert the salt to bendamustine free base, and then allowing an isocyanate-containing compound to polymerize with a polyhydric alcohol surfactant at the water-polyhydric alcohol interface to form stable particles, such as nanocapsules, which encapsulate the drug.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If bendamustine hydrochloride is used in aqueous solutions, then it is soluble and can be administered, but it degrades rapidly leading to short half-life and limited therapeutic use
Solution Approach 1:
The patent uses an intermediary polymeric carrier system that mediates between the aqueous environment and the drug molecule. The carrier particles provide a protective matrix that allows the drug to maintain solubility while preventing rapid degradation, thereby extending half-life. The carrier acts as a protective intermediary that modifies the drug's interaction with the aqueous environment.
Solution Approach 2:
The patent changes the physical and chemical parameters of the drug delivery system by formulating bendamustine hydrochloride as lyophilized particles with controlled size distribution (0.1-100 μm). This parameter change allows the drug to maintain stability while remaining administrable, resolving the contradiction between solubility and half-life.
2Stability of the object's composition
If bendamustine hydrochloride is formulated as lyophilized preparation, then stability is improved, but it requires reconstitution immediately prior to infusion adding complexity
Solution Approach 1:
The patent applies preliminary action by pre-formulating the drug as stable lyophilized particles with controlled size and composition before administration. The particles are prepared in advance with optimal characteristics for both stability and ease of administration, eliminating the need for complex reconstitution steps while maintaining stability.
3Ease of operation
If current formulations are used, then bendamustine can be administered, but the short half-life limits suitability for treating solid tumors
Solution Approach 1:
The patent changes the physical parameters of the drug delivery system by creating particles with specific size distributions (0.1-100 μm) and controlled morphology. These parameter changes enable the formulation to maintain administrability while extending half-life, thereby expanding therapeutic applicability to solid tumors and other indications.
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 approach enhances the stability and bioavailability of bendamustine by forming stable particles that minimize degradation, allowing for improved delivery and extended therapeutic use beyond current limitations.
Implementation Method 1
allowing sufficient time for the isocyanate-containing compound to polymerize with the at least one polyhydric alcohol surfactant at the water-polyhydric alcohol interface to form the bendamustine free base-containing particles
Implementation Method 2
treating the emulsion with an amount of base sufficient to convert the pharmaceutically acceptable salt of bendamustine to bendamustine free base
Implementation Method 3
forming an emulsion by mixing a continuous phase comprising an organic solvent, a dispersed phase comprising an aqueous solution of a pharmaceutically acceptable salt of bendamustine, and at least one polyhydric alcohol surfactant
Data Source
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AI summary
The present invention is directed to particles prepared via the polymerization of at least one surfactant and an isocyanate-containing compound. Pharmaceutical compositions prepared using these particles are also described.