Regadenoson Solid-State Forms Preparation

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Solution Overview

Problem

Current methods for preparing Regadenoson (RDN) do not disclose methanol (MeOH) or dimethyl sulfoxide (DMSO) solvated forms or an anhydrous polymorph, limiting the availability of stable and scalable solid-state forms for pharmaceutical applications.

Innovation Solution

The development of crystalline MeOH or DMSO solvated forms and an anhydrous polymorph of RDN, achieved through specific solvation and evaporation processes, including dissolving RDN in MeOH or DMSO, adding precipitating agents, and controlled drying to isolate stable solid-state forms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional preparation methods are used, then existing polymorphic forms are obtained, but MeOH or DMSO solvated forms and anhydrous polymorph are not disclosed, limiting availability for pharmaceutical applications

Engineering Contradiction:

Improveavailability of solid-state formsVSAvoidstability and scalability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies parameter changes by systematically varying preparation conditions including solvent selection (MeOH, DMSO, water, mixtures), temperature ranges (room temperature to elevated temperatures), pH adjustments, and concentration levels to access different solid-state forms of RDN that were not previously disclosed

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses solvents as intermediaries to facilitate the formation of specific solid-state forms. MeOH and DMSO act as solvating agents that mediate the crystallization process, enabling the formation of stable solvated forms and anhydrous polymorphs with defined structures and properties

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If multiple solid-state forms are developed, then purifiability and stability are improved, but the complexity of characterizing and managing multiple polymorphs increases

Engineering Contradiction:

ImprovestabilityVSAvoidcomplexity of solid-state forms

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the solid-state forms of RDN into distinct categories (MeOH solvate, DMSO solvate, anhydrous polymorph) with well-defined preparation methods and characterization parameters for each, allowing systematic management and selection based on specific pharmaceutical application requirements

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If new solvated forms and anhydrous polymorph are prepared, then pharmaceutical application availability is improved, but the preparation process complexity increases

Engineering Contradiction:

Improvepharmaceutical application availabilityVSAvoidpreparation process simplicity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent employs preliminary actions by pre-selecting appropriate solvent systems and preparation conditions based on desired solid-state form outcomes. The method establishes predetermined protocols for solvent selection, temperature control, and processing parameters that simplify the manufacturing process while ensuring consistent production of the desired polymorphic form

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS11535644B2Solid-state forms of Regadenoson, their use and preparation

Publication Date: 2022.12.27 MACFARLAN SMITH

AI summary

The invention relates to a crystalline methanol or dimethyl sulfoxide solvated form of regadenoson and an anhydrous polymorph of regadenoson. The invention is also directed to the preparation of the methanol or dimethyl sulfoxide solvated and anhydrous solid-state forms of regadenoson. In particular, the invention relates to the preparation of the anhydrous polymorph of regadenoson in a stable form from the dimethyl sulfoxide solvated form of regadenoson, which preparation is purifiable and scalable.