Rifaximin κ Polymorph Humidity Stability
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Solution Overview
Problem
The existing polymorphic forms of Rifaximin are not stable in humid environments, affecting their storage and pharmacological properties, and there is a need for new polymorphs with improved stability and bioavailability.
Innovation Solution
A new polymorphic form of Rifaximin, designated κ, is identified with a specific XRD spectrum and a process involving suspension in 1,2-dimethoxyethane followed by drying, which maintains crystallinity even at elevated humidity levels, ensuring stability and prolonged storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing polymorphic forms of Rifaximin are used, then the compound can be formulated for pharmaceutical applications, but the forms are not stable in humid environments affecting storage and pharmacological properties
Solution Approach 1:
The patent applies parameter changes by modifying the crystalline structure parameters of Rifaximin to create a new polymorphic form (κ) with different packing arrangements and intermolecular interactions. This structural parameter change results in enhanced stability against humidity, as the new crystalline configuration resists moisture-induced degradation that affects previous polymorphic forms.
Solution Approach 2:
The invention creates a composite crystalline structure where Rifaximin molecules are arranged in a specific polymorphic configuration (κ-form) that combines multiple stabilizing interactions. This composite structural arrangement, characterized by specific XRD peaks and molecular packing, provides inherent protection against humidity while maintaining the pharmacological activity of the compound.
2Duration of action of stationary object
If a new polymorphic form is developed to improve stability, then storage duration can be prolonged, but the process complexity increases
Solution Approach 1:
The patent applies preliminary action by establishing specific crystallization conditions (solvent selection, temperature control, pH adjustment) during the manufacturing process that directly yield the stable κ-polymorph. By pre-configuring these process parameters, the method ensures formation of the desired stable form from the outset, avoiding subsequent stability issues without requiring complex post-processing or stabilization steps.
Solution Approach 2:
The invention utilizes phase transitions by controlling the crystallization process from solution to solid state, directing the formation of the κ-polymorph through specific solvent evaporation and cooling conditions. This controlled phase transition ensures the compound adopts the stable crystalline configuration during manufacturing, extending storage duration while maintaining a relatively straightforward process.
3Reliability
If polymorphism is exploited to improve pharmacological properties, then bioavailability can be enhanced, but the number of possible forms makes prediction difficult
Solution Approach 1:
The patent applies local quality by focusing on specific local molecular interactions and packing arrangements within the κ-polymorph structure. By optimizing local crystalline features (specific hydrogen bonding patterns, molecular orientations, and packing densities), the invention enhances bioavailability through improved dissolution characteristics while managing the overall polymorph variability through targeted structural design.
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 polymorph κ of Rifaximin remains stable under high humidity conditions, allowing for prolonged storage and improved pharmaceutical formulations with enhanced stability and bioavailability.
Implementation Method 1
polymorphism derives from the possibility, for the molecule, of modifying its conformation, giving rise to different intermolecular and intramolecular interaction schemes, in particular, hydrogen bonds, which stabilise different spatial arrangements of the atoms
Implementation Method 2
which has a powder XRD spectrum with peaks at the values of angle 2θ of 5.3°, 6.8°, 7.8°, 8.5°, 9.3°
Data Source
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AI summary
The present invention relates to a new polymorph of Rifaximin, designated ?, and to a process for the preparation thereof. Under certain aspects, the invention also relates to pharmaceutical compositions comprising an effective amount of the polymorphic form ? of Rifaximin and a pharmaceutically acceptable carrier and its uses in the treatment of gastrointestinal conditions.