Polyoxazoline Polymers Inhibit Crystallization in Transdermal Carriers

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Solution Overview

Problem

Transdermal drug delivery systems face challenges in preventing crystal formation and degradation of active agents during storage, leading to inadequate delivery rates and skin irritation, especially with hydrophobic drugs like hormones and steroidal agents, which are poorly soluble in polymeric compositions.

Innovation Solution

Incorporating polyoxazoline polymers, such as poly(2-ethyl-2-oxazoline), into the carrier composition to inhibit crystallization and degradation, maintaining active agents in a solubilized form and enhancing their solubility and stability, thereby ensuring a controlled and prolonged release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If high concentrations of hydrophobic active agents are incorporated into the carrier composition to maximize delivery rates, then delivery rate is improved, but crystal formation and degradation occur during storage

Engineering Contradiction:

Improvedelivery rateVSAvoidstability of active agent

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent introduces polyoxazoline polymers as intermediary substances that mediate between the hydrophobic active agents and the polymeric carrier composition. These polymers act as solubilizing agents that prevent crystal formation while maintaining high concentrations of active agents, thereby achieving both high delivery rates and storage stability simultaneously

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the carrier composition by incorporating polyoxazoline polymers with specific molecular weights and compositions. This parameter change enables the system to maintain supersaturated concentrations of hydrophobic active agents without crystallization, resolving the contradiction between delivery rate and stability

Inventive Principle:

Principle #35Parameter changes

2Stability of the object's composition

If low concentrations of active agents are used to prevent crystal formation, then stability is improved, but delivery rate becomes inadequate

Engineering Contradiction:

Improvestability of active agentVSAvoiddelivery rate

Core Design Contradiction:

Stability of the object's compositionVSProductivity

Solution Approach 1:

Polyoxazoline polymers serve as intermediary solubilizing agents that enable the carrier composition to maintain high concentrations of active agents in a stable, non-crystalline state. This intermediary substance allows the system to achieve adequate delivery rates without sacrificing stability

Inventive Principle:

Principle #24Intermediary (Mediator)

3Duration of action of moving object

If the active agent is maintained at or near saturation solubility to achieve prolonged continuous administration, then duration of action is improved, but recrystallization occurs during storage

Engineering Contradiction:

Improveduration of continuous administrationVSAvoidresistance to recrystallization

Core Design Contradiction:

Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary anti-action by incorporating polyoxazoline polymers into the carrier composition before the active agent can recrystallize during storage. These polymers preemptively prevent crystal nucleation and growth, allowing the system to maintain supersaturated concentrations for prolonged periods without recrystallization

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

Polyoxazoline polymers act as intermediary substances that stabilize the supersaturated state of the active agent, enabling continuous administration for extended durations while preventing recrystallization during storage periods

Inventive Principle:

Principle #24Intermediary (Mediator)

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 use of polyoxazoline polymers effectively suppresses crystal formation and degradation, maintaining active agents in a solubilized state, enhancing in vitro flux rates, and achieving a sustained zero-order kinetic drug delivery for extended periods without recrystallization, improving therapeutic efficacy and reducing skin irritation.

Implementation Method 1

the active agent remain in non-crystalline or dissolved form in the carrier composition prior to use

Methodology Applied

Scientific EffectSolubilization: Solvation

Implementation Method 2

the carrier composition must not promote drug crystal growth or formation, especially during storage of the system prior to use

Methodology Applied

Scientific EffectCrystallization inhibition: Crystallisation

Implementation Method 3

from which the drug is delivered at therapeutically effective amounts by absorption through skin or mucosa of the user

Methodology Applied

Scientific EffectAbsorption: Absorption (physical)

Implementation Method 4

enhancing in vitro flux rates

Methodology Applied

Scientific EffectDiffusion: Diffusion

Data Source

PatentUS8586080B1Inhibiting crystallization of steroidal hormones in transdermal delivery systems

Publication Date: 2013.11.19 NOVEN PHARMACEUTICALS INC

AI summary

Compositions and methods for the continuous and controlled transdermal delivery of an active agent from a pharmaceutically acceptable carrier composition comprising a polyoxazoline polymer, wherein the active drug incorporated in the carrier composition of the transdermal system remains substantially solubilized and stable during storage prior to use.