Funapide Solid State Forms for Stability and Solubility

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Solution Overview

Problem

Current pharmaceutical formulations of funapide lack optimal solid state forms that provide improved handling, stability, and bioavailability for treating sodium channel-mediated diseases such as pain, central nervous conditions, and cardiovascular issues.

Innovation Solution

Development of specific solid state forms of funapide, including crystalline forms A0 and B0, and the amorphous form, characterized by unique X-ray powder diffraction patterns, DSC thermograms, and Raman shift spectra, which are highly soluble and physically stable, combined with pharmaceutically acceptable excipients to enhance processing and therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional pharmaceutical formulations of funapide are used, then the basic therapeutic function is achieved, but the chemical and physical stability, solubility, and bioavailability are not optimized

Engineering Contradiction:

Improvechemical and physical stabilityVSAvoidformulation processing

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by discovering and utilizing different polymorphic forms (Form A0, Form B0, amorphous form) of funapide, each with distinct crystal structures and physical properties. By changing the solid state form parameter, the formulation achieves improved chemical stability, physical stability, solubility, and bioavailability while maintaining manufacturability through established pharmaceutical processing techniques.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If different solid state forms of funapide are developed, then solubility and bioavailability are improved, but the complexity of characterization and quality control increases

Engineering Contradiction:

Improvesolubility and bioavailabilityVSAvoidcharacterization and quality control

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent applies local quality by providing specific characterization data for each polymorphic form (Form A0 with its distinct XRPD pattern, Form B0 with its distinct XRPD pattern, and amorphous form with its DSC profile). This allows quality control to be tailored to each specific form, ensuring that the appropriate level of characterization is applied to maintain solubility and bioavailability benefits while managing complexity through form-specific protocols.

Inventive Principle:

Principle #3Local quality

3Duration of action of stationary object

If polymorphic forms with improved stability are selected, then shelf-life is extended, but the processing and handling characteristics may vary

Engineering Contradiction:

Improveshelf-lifeVSAvoidprocessing and handling characteristics

Core Design Contradiction:

Duration of action of stationary objectVSEase of operation

Solution Approach 1:

The patent applies inversion by selecting the amorphous form, which typically has superior solubility and bioavailability compared to crystalline forms, while achieving enhanced stability through specific formulation approaches. This reverses the conventional wisdom that crystalline forms are always more stable, demonstrating that the amorphous form can provide both stability and improved processing characteristics when properly formulated.

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS10118932B2Solid state forms of spiro-oxindole compounds

Publication Date: 2018.11.06 PACIRA THERAPEUTICS INC

AI summary

The present invention provides solid state forms of certain spiro-oxindole compounds, such as funapide and the racemic mixture of funapide and its corresponding (R) enantiomer, pharmaceutical compositions comprising the solid state forms and processes for preparing the solid state forms and the pharmaceutical compositions.