Viloxazine Salts Stability and Solubility
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Solution Overview
Problem
There is a need for novel salts and crystalline forms of viloxazine with improved properties for use in drug products, particularly for the treatment of attention-deficit hyperactivity disorder (ADHD), as existing forms may be sensitive to temperature, humidity, and light, and exhibit variations in stability, solubility, and physical characteristics that affect drug performance.
Innovation Solution
Development of viloxazine salts with organic acids such as fumaric acid, DL-tartaric acid, naphthalene-2-sulfonic acid, and citric acid, characterized by specific PXRD diffractogram peaks, which provide improved stability and solubility, and are used in pharmaceutical compositions for enhanced drug formulation and manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing viloxazine forms are used, then the drug can be provided for ADHD treatment, but the forms exhibit sensitivity to temperature, humidity, and light with variations in stability
Solution Approach 1:
The patent applies parameter changes by converting viloxazine into different salt forms (fumarate, tartrate, tosylate, citrate) with specific crystalline structures. Each salt form has distinct crystal packing arrangements that fundamentally alter the physical and chemical parameters of the drug substance, resulting in improved stability profiles against temperature, humidity, and light while maintaining therapeutic efficacy.
Solution Approach 2:
The patent creates composite crystalline structures by combining viloxazine with various counterions (fumarate, tartrate, tosylate, citrate) in specific stoichiometric ratios. These composite crystalline forms exhibit enhanced stability properties compared to the parent compound, as the composite structure provides protection against environmental factors through improved crystal packing and reduced molecular mobility.
2Reliability
If different salt and crystalline forms are developed, then improved stability and solubility properties are achieved, but the complexity of characterization and manufacturing increases
Solution Approach 1:
The patent employs preliminary action by establishing comprehensive characterization protocols and manufacturing procedures during the development phase. Detailed PXRD patterns, DSC curves, and solubility profiles are predetermined for each salt form, allowing for streamlined quality control and manufacturing processes. The specific crystalline forms are designed with distinct characterization fingerprints that simplify identification and quality assurance.
Solution Approach 2:
The patent segments the viloxazine drug substance into distinct salt forms with well-defined properties. Each salt (fumarate, tartrate, tosylate, citrate) is characterized as a separate entity with unique PXRD patterns, solubility profiles, and stability characteristics. This segmentation allows for optimized formulation approaches tailored to each salt form's specific properties, simplifying the overall development and manufacturing process.
Data Source
AI summary
The present invention provides novel salts of viloxazine and crystalline forms thereof. Specific salts of viloxazine provided by the present invention include fumarate, hemi-DL-tartrate, naphthalene-2-sulfonate, and citrate. Also provided are pharmaceutical compositions including the viloxazine salts and crystalline forms thereof and the use of these salts in the treatment of attention-deficit hyperactivity disorder in a human subject suffering therefrom.