Pharmaceutical Composition for Sustained Solubility

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Solution Overview

Problem

Current pharmaceutical compositions that enhance the solubility and bioavailability of poorly soluble active ingredients in gastric juice fail to maintain this increased solubility over a prolonged period, leading to reduced bioavailability as the active ingredients quickly recrystallize or precipitate, making it difficult to achieve the desired blood level for therapeutic effects.

Innovation Solution

A pharmaceutical composition comprising a mixture of cationic, water-soluble (meth)acrylate copolymers, water-insoluble polymers, and active ingredients with low solubility in demineralized water, where the water-insoluble polymer and active ingredient are in a ratio of up to 3.5:1, and the copolymers are in a 40:60 to 99:1 ratio, releasing the active ingredient in a medium buffered to pH 1.2 at a concentration at least sixteen times its initial solubility value after 2 hours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If water-soluble polymers are used to enhance solubility of poorly soluble active ingredients, then solubility and bioavailability increase initially, but solubility is not maintained over prolonged periods leading to recrystallization

Engineering Contradiction:
Improvesolubility of active ingredientVSAvoidstability of dissolved state
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The invention uses a composite polymer system combining water-soluble cationic polymers (for initial solubility enhancement) with water-insoluble polymers (for long-term stability). This composite approach allows the formulation to achieve both high initial solubility and sustained stability, preventing the recrystallization problem that occurs with water-soluble polymers alone. The water-insoluble polymer acts as a stabilizing matrix that maintains the active ingredient in dissolved state over prolonged periods.

Inventive Principle:
Principle #40Composite materials

2Reliability

If polymers are used to increase bioavailability, then therapeutic blood levels can be achieved, but the effect is temporary and bioavailability decreases over time

Engineering Contradiction:
ImprovebioavailabilityVSAvoidduration of sustained bioavailability
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The invention achieves continuous bioavailability enhancement by combining polymers with complementary properties. The water-soluble cationic polymer provides immediate solubility enhancement for rapid absorption, while the water-insoluble polymer provides sustained stabilization over extended periods. This continuous action ensures therapeutic blood levels are maintained from the initial release through prolonged circulation, eliminating the temporary effect seen with single-polymer systems.

Inventive Principle:
Principle #20Continuity of useful action

3Productivity

If only water-soluble polymers are used, then initial solubility enhancement is achieved, but long-term stability and sustained release are compromised

Engineering Contradiction:
Improverate of dissolutionVSAvoidduration of solubility maintenance
Core Design Contradiction:
ProductivityVSDuration of action of moving object

Solution Approach 1:

The invention segments the polymer system into two distinct functional components: water-soluble cationic polymers that rapidly dissolve to enhance initial solubility and promote quick absorption, and water-insoluble polymers that provide long-term structural stability and sustained release. This segmentation allows each polymer type to optimize its specific function without compromising the other, achieving both rapid dissolution kinetics and prolonged solubility maintenance.

Inventive Principle:
Principle #1Segmentation

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 composition maintains the increased solubility of active ingredients in gastric juice for at least 120 minutes, preventing recrystallization and enhancing bioavailability, ensuring stable solubility even after transitioning to intestinal pH values, thereby achieving and sustaining therapeutic blood levels.

Implementation Method 1

releasing the active ingredient contained in a dissolved form in a medium buffered to pH 1.2 in a concentration which, after 2 hours at pH 1.2, corresponds to at least sixteen times the solubility value of the active ingredient alone at pH 1.2

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

maintains the increased solubility of active ingredients in gastric juice for at least 120 minutes, preventing recrystallization

Methodology Applied
Scientific EffectSteric stabilization:

Data Source

PatentEP1978936B1Pharmaceutical compositions containing mixtures of polymers and active agents poorly soluble in water
Publication Date: 2013.07.10 ROHM GMBH

AI summary

The invention relates to a pharmaceutical composition, containing a mixture of at least one cationic water-soluble (meth)acrylate copolymer, at least one water-insoluble polymer and at least one active agent with a solubility in demineralised water of 3,3 g/l or less, characterised in that the water-insoluble polymer and the active agent are present in a ratio of at most 3.5 to 1 parts by weight and the pharmaceutical composition has the following properties: the contained active agent is released in dissolved form in a medium buffered at pH 1.2, which, after 2 hours at pH 1.2, corresponds to at least 16 times the solubility value of the active agent alone at pH 1.2.