Lyophilized Polymeric Nanoparticles Rapid Reconstitution

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Solution Overview

Problem

Existing methods for preparing lyophilized polymeric nanoparticles are inefficient, requiring longer reconstitution times due to instability in aqueous solutions, and often necessitate additional excipients like polyethylene glycol to improve redissolution ability.

Innovation Solution

A lyophilization process involving a specific sequence of freezing, annealing, and drying steps for a solution containing amphiphilic block copolymers and polylactic acid derivatives, which allows for rapid reconstitution of biodegradable polymeric nanoparticles within 5 minutes under atmospheric pressure without the need for extra excipients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If polymeric nanoparticles are formulated in freeze-dried form to improve stability, then stability in aqueous solution is improved, but reconstitution time increases

Engineering Contradiction:
Improvestability in aqueous solutionVSAvoidreconstitution time
Core Design Contradiction:
Stability of the object's compositionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by incorporating a lyophilization aid during the freeze-drying process that promotes rapid reconstitution. The aid is预先 added to the formulation to ensure fast redissolution upon reconstitution, directly addressing the time loss issue while maintaining stability during storage.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes physical and chemical parameters of the formulation by adjusting the type and amount of lyophilization aid, as well as the freezing and drying conditions. These parameter modifications optimize both stability during storage and reconstitution speed, resolving the contradiction between these two requirements.

Inventive Principle:
Principle #35Parameter changes

2Loss of time

If additional excipients like polyethylene glycol are added to improve redissolution ability, then reconstitution speed is improved, but device complexity and formulation complexity increases

Engineering Contradiction:
Improvereconstitution timeVSAvoidformulation complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent extracts the unnecessary complexity by eliminating the need for multiple excipients like polyethylene glycol. Instead, it uses a specifically designed lyophilization aid that achieves rapid reconstitution alone, simplifying the formulation while maintaining the desired reconstitution speed.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The lyophilization aid is selected to perform multiple functions: it acts as a stabilizer during freeze-drying, promotes rapid reconstitution, and eliminates the need for additional excipients. This self-service approach reduces formulation complexity while achieving the reconstitution goal.

Inventive Principle:
Principle #25Self-service

3Manufacturing precision

If polymeric nanoparticles are used for drug delivery to achieve target site specificity, then delivery precision is improved, but stability in aqueous solution deteriorates

Engineering Contradiction:
Improvetarget site specificityVSAvoidstability in aqueous solution
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent creates a stable environment for the polymeric nanoparticles during storage by using freeze-dried formulation with lyophilization aid, which prevents aggregation and degradation in aqueous solution. This inert-like stable state allows the nanoparticles to maintain their target site specificity capability without deteriorating stability.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent modifies the physical state and chemical environment parameters of the nanoparticle formulation to achieve both stability and functionality. By controlling the lyophilization process and selecting appropriate aids, the formulation maintains stability during storage while preserving the target site delivery capability upon reconstitution.

Inventive Principle:
Principle #35Parameter changes

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 results in a lyophilizate with enhanced biocompatibility and rapid reconstitution, suitable for containing poorly water-soluble drugs, with improved stability and reduced reconstitution time, maintaining the cake form and porosity for efficient drug delivery.

Implementation Method 1

a first freezing step wherein the aqueous solution of polymeric nanoparticle is frozen

Methodology Applied
Scientific EffectFreezing: Freezing

Implementation Method 2

a primary drying step wherein the frozen aqueous solution of polymeric nanoparticle is dried under reduced pressure

Methodology Applied
Scientific EffectFreeze drying: Freeze Drying

Implementation Method 3

an annealing step wherein the frozen aqueous solution of polymeric nanoparticle is heated to a higher temperature

Methodology Applied
Scientific EffectAnnealing: Annealing

Data Source

PatentEP3241546B1Polymer nanoparticle freeze-dried product, and preparation method therefor
Publication Date: 2021.02.17 SAMYANG BIOPHARMLS CORP
  • EP3241546B1 patent drawingFigure 1
  • EP3241546B1 patent drawingFigure 2
  • EP3241546B1 patent drawingFigure 3

AI summary

The present invention relates to a polymer nanoparticle freeze-dried product, and a preparation method therefor, the polymer nanoparticle freeze-dried product being obtainable by treating, through a freeze-drying process comprising an annealing step, a polymer nanoparticle aqueous solution comprising an amphiphilic block copolymer, a polylactic acid derivative having a carboxyl terminal group, and a freeze-drying adjuvant, wherein the polymer nanoparticle freeze-dried product is reconstituted within five minutes upon reconstitution by means of an aqueous solvent under atmospheric pressure.