Semi-ordered Drug Polymers for Dissolution Stability

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Low-solubility drugs often exhibit poor bioavailability and irregular absorption due to their crystalline form, which is not physically or chemically stable, leading to rapid crystallization and degradation, thereby limiting their effectiveness.

Innovation Solution

A pharmaceutical composition comprising a low-solubility drug in a semi-ordered state combined with a concentration-enhancing polymer, where at least 20 wt% of the drug is in a semi-ordered state, providing enhanced stability and bioavailability by maintaining improved dissolution properties over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the drug is formulated in amorphous form to increase dissolution rate and concentration, then the dissolution performance is improved, but the physical stability deteriorates leading to rapid crystallization

Engineering Contradiction:

Improvedissolution rateVSAvoidphysical stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by transforming the drug from a completely amorphous state to a semi-ordered state with intermediate structural characteristics. This intermediate state maintains enhanced dissolution properties compared to crystalline forms while exhibiting improved physical stability against crystallization, effectively resolving the contradiction between dissolution rate and physical stability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system where the drug exists in a semi-ordered state within a polymer matrix. This composite structure combines the advantages of amorphous dispersions (enhanced solubility and dissolution) with improved stability, as the polymer matrix restrains molecular mobility and prevents complete crystallization while maintaining drug availability.

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If the drug is formulated in crystalline form to ensure physical stability, then the stability is improved, but the bioavailability and dissolution performance deteriorate

Engineering Contradiction:

Improvephysical stabilityVSAvoidbioavailability

Core Design Contradiction:

Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent changes the structural parameter of the drug from highly ordered crystalline form to semi-ordered form. This parameter change reduces the stability-crystallization driving force while maintaining sufficient structural order to prevent complete amorphous collapse, thereby achieving both acceptable stability and improved bioavailability through enhanced dissolution.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If the drug loading is increased to improve therapeutic effectiveness, then the effectiveness is improved, but the stability deteriorates due to increased tendency to crystallize

Engineering Contradiction:

Improvedrug loadingVSAvoidstability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

By changing the drug's structural parameter to semi-ordered state, the patent increases the energy barrier for crystallization. This allows higher drug loading levels to be achieved while maintaining stability, as the semi-ordered structure requires more significant reorganization to transition to the crystalline state, thereby delaying or preventing crystallization even at higher concentrations.

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 improved stability and bioavailability by maintaining enhanced drug concentrations and dissolution performance, allowing for higher drug loadings while preventing crystallization and degradation, thus overcoming the limitations of conventional solid amorphous dispersions.

Implementation Method 1

the amorphous form may temporarily provide a greater aqueous concentration of drug relative to the equilibrium concentrations obtained by dissolution of the crystalline drug form

Methodology Applied

Scientific EffectAmorphous state:

Implementation Method 2

the initially enhanced drug concentration is only temporary and quickly returns to the lower equilibrium concentration

Methodology Applied

Scientific EffectCrystallization: Crystallisation

Implementation Method 3

the solid drug may not be physically stable in the amorphous form. Often the crystalline form of the drug has a lower free energy, and thus over time the amorphous drug will tend to crystallize

Methodology Applied

Scientific EffectPhysical stability:

Implementation Method 4

at least a portion of said drug is present in drug-rich regions and said drug-rich regions are interspersed throughout drug-poor, polymer-rich regions, and wherein at least 20 wt % of said low-solubility drug is in a semi-ordered state

Methodology Applied

Scientific EffectSemi-ordered state:

Data Source

PatentUS8257739B2Pharmaceutical compositions of semi-ordered drugs and polymers

Publication Date: 2012.09.04 PFIZER PROD INC

AI summary

A solid composition of a low-solubility drug and a concentration-enhancing polymer has a portion of the drug in a semi-ordered state.