Polyvinyl Alcohol Solid Dispersion for Poorly Soluble Drug

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Solution Overview

Problem

Current methods for improving the solubility of poorly-soluble drugs are insufficient, as existing compositions using polyvinyl alcohol do not effectively enhance drug solubility.

Innovation Solution

A pharmaceutical composition is developed using a poorly-soluble drug and polyvinyl alcohol with a saponification degree of 63 mol% to 67 mol%, forming a solid dispersion that increases the drug's solubility by maintaining the drug in an amorphous form.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If polyvinyl alcohol is used as a carrier for solid dispersion, then the drug can be dispersed in solid form, but the solubility enhancement is insufficient

Engineering Contradiction:
Improvesolubility enhancementVSAvoidcarrier selection complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by specifying a narrow saponification degree range (63-67 mol%) for polyvinyl alcohol. This precise parameter control transforms the generic carrier approach into a targeted solution, where the specific chemical composition parameters of the carrier directly determine the amorphous state stability and solubility enhancement effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements local quality by focusing on a specific property range of the carrier material. Instead of using polyvinyl alcohol with any saponification degree, the invention identifies and utilizes the optimal local range (63-67 mol%) where the carrier exhibits maximum effectiveness in maintaining drug amorphous state and enhancing solubility.

Inventive Principle:
Principle #3Local quality

2Reliability

If the drug is crystallized for stability, then the drug maintains structural integrity, but solubility is reduced

Engineering Contradiction:
Improvedrug stabilityVSAvoiddissolved concentration
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent utilizes phase transitions by transforming the drug from crystalline state to amorphous state within the carrier matrix. This phase change eliminates the ordered crystal structure that limits solubility while maintaining the drug in a metastable amorphous form that provides both enhanced dissolution and adequate stability through the protective carrier environment.

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The polyvinyl alcohol carrier acts as an intermediary that stabilizes the amorphous drug form. The carrier material mediates between the conflicting requirements of crystalline stability and amorphous solubility by providing a matrix that prevents drug recrystallization while maintaining the drug in a highly soluble amorphous state.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If a solid dispersion is prepared with appropriate carrier, then drug solubility is enhanced, but the carrier must be selected from specific saponification degree range

Engineering Contradiction:
ImprovesolubilityVSAvoidcarrier specification complexity
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent simplifies manufacturing by establishing clear parameter specifications for the carrier. The saponification degree range (63-67 mol%) serves as a definitive selection criterion that guides manufacturers in choosing the appropriate polyvinyl alcohol grade, eliminating the need for complex empirical optimization while ensuring consistent solubility enhancement results.

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 composition achieves a significant increase in solubility, with a 6-fold or more increase in dissolved concentration compared to crystalline drug substances, demonstrating improved pharmacological effectiveness.

Implementation Method 1

a method of preparing a solid dispersion of a poorly-soluble drug with a carrier, are known. Further, compositions, in which the solubility of a drug is improved by using polyvinyl alcohol as a carrier of a solid dispersion

Methodology Applied
Scientific EffectAmorphous form: Metastability

Implementation Method 2

a pharmaceutical composition comprising a poorly-soluble drug and polyvinyl alcohol having a saponification degree of 63 mol% or more and 67 mol% or less, wherein the poorly-soluble drug has a solubility of 10 μg/mL or less in water

Methodology Applied
Scientific EffectSolid dispersion: Dispersion (of waves)

Data Source

PatentEP3616722B1Pharmaceutical composition
Publication Date: 2023.10.25 ASTELLAS PHARMA INC
  • EP3616722B1 patent drawingFigure 1~3
  • EP3616722B1 patent drawingFigure 4~5
  • EP3616722B1 patent drawingFigure 6~7

AI summary

Provided is a pharmaceutical composition in which the solubility and/or dissolution properties of a poorly-soluble drug can be improved. The pharmaceutical composition comprises a poorly-soluble drug, and polyvinyl alcohol having a saponification degree of 63 mol% or more and 67 mol% or less.