Eluxadoline Solid State Forms for IBS-D Stability
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Solution Overview
Problem
There is a need for additional solid state forms of Eluxadoline to improve its processing properties, stability, and bioavailability for the treatment of irritable bowel syndrome with diarrhea (IBS-D), as existing forms may have varying physical and chemical properties that affect handling, dissolution, and shelf-life.
Innovation Solution
Development of new solid state forms of Eluxadoline, including crystalline and amorphous forms, characterized by specific X-ray powder diffraction patterns and thermal stability, which can be used to prepare pharmaceutical compositions and formulations, enhancing their chemical and polymorphic stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of Eluxadoline are used, then the treatment of IBS-D can be provided, but the processing properties, stability, and bioavailability are limited due to varying physical and chemical properties
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple polymorphic forms (alpha, beta, gamma, delta, epsilon, zeta, eta, theta, iota, kappa, lambda, mu, nu, xi, omicron, pi, rho, sigma, tau, upsilon, phi, chi, omega) of Eluxadoline, each with distinct crystal structures and physical properties. By changing the solid state form parameter, the patent improves processing properties, stability, and bioavailability while maintaining the therapeutic effect for IBS-D treatment
2Duration of action of stationary object
If existing solid state forms of Eluxadoline are used, then pharmaceutical compositions can be prepared, but the dissolution profile and shelf-life are suboptimal
Solution Approach 1:
The patent changes the solid state form parameter to achieve optimal balance between shelf-life and dissolution profile. Different polymorphic forms exhibit varying dissolution rates and stability characteristics, allowing selection of the most appropriate form for specific formulation requirements and intended use conditions
Solution Approach 2:
The patent performs preliminary characterization of multiple polymorphic forms including X-ray diffraction patterns, thermal analysis (DSC, TGA), and solubility studies before selecting the optimal form for pharmaceutical development. This preliminary action enables informed decisions about which polymorphic form to use for maximizing both shelf-life and dissolution performance
3Ease of operation
If additional solid state forms of Eluxadoline are developed, then processing and handling characteristics are improved, but the complexity of characterizing and selecting the appropriate form increases
Solution Approach 1:
The patent systematically characterizes each polymorphic form using a standardized set of parameters including X-ray diffraction patterns, melting points, thermal stability data, and solubility measurements. This systematic approach to parameter changes creates a comprehensive reference framework that simplifies the selection and identification of appropriate forms for specific applications
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 new solid state forms of Eluxadoline provide improved stability, dissolution profiles, and handling characteristics, leading to more effective pharmaceutical compositions for treating IBS-D, with specific forms like alpha, I, II, III, and IV exhibiting high chemical purity and stability under various conditions.
Implementation Method 1
X-ray diffraction pattern
Implementation Method 2
X-ray powder diffraction patterns having peaks at
Implementation Method 3
thermogravimetric analysis—'TGA'
Implementation Method 4
differential scanning calorimetry—'DSC'
Data Source
AI summary
Disclosed are solid state forms of Eluxadoline, processes for their preparations, compositions comprising them and their medical use. The present invention also encompasses solid state forms of Eluxadoline for use in the preparation of other solid state forms of Eluxadoline, particularly form alpha.