Sustained Release Dosage Forms for Low Solubility APIs

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Solution Overview

Problem

Current sustained release pharmaceutical formulations are inadequate for low solubility active pharmaceutical ingredients (APIs) as existing technologies often compromise solubility rather than enhance it, leading to inconsistent drug release and therapeutic efficacy.

Innovation Solution

A method involving the formation of API-cyclodextrin complexes to enhance solubility, followed by incorporation into sustained release formulations using techniques like diffusion membrane technology, ensuring stable and controlled release profiles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional sustained release formulations are used for low solubility APIs, then release duration is extended, but solubility and bioavailability deteriorate

Engineering Contradiction:

Improverelease durationVSAvoidsolubility and bioavailability

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent uses cyclodextrins as intermediary molecules that form inclusion complexes with low solubility APIs. The cyclodextrin cavity encapsulates the hydrophobic API molecule, while the hydrophilic exterior of the cyclodextrin enhances solubility. This mediator approach allows the API to maintain its sustained release properties while achieving improved solubility and bioavailability through the complexing agent.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite system consisting of the API-cyclodextrin inclusion complex incorporated into a sustained release matrix formulation. This composite material combines the solubility-enhancing properties of the cyclodextrin complex with the release-controlling characteristics of the matrix system, achieving both improved solubility and sustained release performance simultaneously.

Inventive Principle:

Principle #40Composite materials

2Reliability

If solubility enhancement techniques are applied to low solubility APIs, then bioavailability improves, but sustained release properties deteriorate

Engineering Contradiction:

ImprovebioavailabilityVSAvoidsustained release properties

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the physical-chemical parameters of the API by forming an inclusion complex with cyclodextrin, which changes the dissolution behavior and bioavailability without fundamentally altering the sustained release mechanism. The complexation enhances solubility parameters while the matrix formulation maintains the release duration parameters, achieving both goals through parameter optimization.

Inventive Principle:

Principle #35Parameter changes

3Duration of action of moving object

If matrix formulations are used for sustained release, then release duration is extended, but manufacturing complexity increases

Engineering Contradiction:

Improverelease durationVSAvoidmanufacturing complexity

Core Design Contradiction:

Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent combines the solubility enhancement function (cyclodextrin complexation) with the sustained release function (matrix formulation) into a single integrated dosage form. This merging eliminates the need for separate solubility enhancement steps and simplifies the manufacturing process while achieving both solubility improvement and sustained release in one formulation system.

Inventive Principle:

Principle #5Merging (Combining)

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 approach significantly increases the solubility and bioavailability of low solubility APIs, providing consistent and prolonged therapeutic effects with reduced variability, thus overcoming the limitations of existing formulations.

Implementation Method 1

at least one active pharmaceutical ingredient (API) in a non-covalent inclusion complex with a complex-forming agent together forming an API-inclusion complex

Methodology Applied

Scientific EffectInclusion complex formation: Absorption (physical)

Implementation Method 2

diffusion membrane technology

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 3

release delaying layer (e.g., due to enteric coating)

Methodology Applied

Scientific EffectPermeation: Permeation

Data Source

PatentUS20240350642A1Sustained release dosage forms for low solubility compounds and methods for preparing of these sustained release dosage forms

Publication Date: 2024.10.24 EMOVIAR PHARMACON GMBH

AI summary

The present invention relates to a solid oral pharmaceutical with a novel, well defined method to enhance solubility of active pharmaceutical ingredients (API) with low solubility in aqueous media and use those enhanced API in a new approach of preparing modified and sustained release pharmaceutical formulation for API which are regularly not suitable for sustained release formulations because of their low solubility. This invention is applicable for small molecule API (molecular weight <1000) for which the solubility can be enhanced by formation of a e.g., Cyclodextrin Complex regardless which Cyclodextrin or derivate thereof is employed according to the method described in this invention. Small molecule API falling in this category can be found in a wide range of indications.