Oxime Ether Solid Forms Enhance Stability and Bioavailability

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Solution Overview

Problem

There is a need for novel drug products to treat multiple sclerosis and other autoimmune diseases affecting the central nervous system, as existing technologies struggle to predict and prepare stable crystalline forms of pharmaceutical compounds, which are crucial for effective treatment.

Innovation Solution

Development of solid forms comprising (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid, including crystalline and amorphous forms, characterized by specific X-ray powder diffraction patterns and thermal properties, for use in pharmaceutical compositions to treat autoimmune diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If alternative solid forms are developed to enhance physical and chemical properties, then stability and bioavailability are improved, but the complexity of identifying and selecting the appropriate solid form increases

Engineering Contradiction:

ImprovestabilityVSAvoidcomplexity of identifying and selecting solid form

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by systematically varying physical and chemical parameters to transform the compound into different solid forms (crystalline, amorphous, solvates, hydrates). Each solid form exhibits different physical and chemical properties, allowing optimization of stability and bioavailability through selective parameter modification during formulation development

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by creating pharmaceutical compositions that combine the active compound with specific solid forms (crystalline or amorphous). These composite structures integrate the therapeutic agent with excipients in controlled solid-state configurations, enhancing overall formulation stability while managing the complexity through standardized composite material approaches

Inventive Principle:

Principle #40Composite materials

2Reliability

If crystalline forms are selected for physical or chemical stability, then reliability is improved, but dissolution profile may be compromised compared to amorphous solids

Engineering Contradiction:

Improvephysical or chemical stabilityVSAvoiddissolution profile

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies dynamics by enabling flexible selection between crystalline and amorphous solid forms based on the specific therapeutic requirements. The formulation approach allows dynamic adjustment of solid-state characteristics to optimize the balance between stability and dissolution, rather than being constrained to a single fixed form

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent utilizes parameter changes to modify the solid-state properties of the compound. By controlling crystallization conditions, solvent selection, and processing parameters, the formulation can transition between different solid forms (crystalline, amorphous, solvates, hydrates), each offering different combinations of stability and dissolution characteristics for optimized therapeutic performance

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11629124B2Solid forms comprising an oxime ether compound, compositions and methods of use thereof

Publication Date: 2023.04.18 NOVARTIS AG

AI summary

Provided herein are formulations, processes, solid forms and methods of use relating to (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid.