Posiphen D-Tartrate Crystal Forms for Solubility-Stability Balance

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Solution Overview

Problem

There is a need to identify novel solid forms of posiphen D-tartrate with advantageous chemical and physical properties, as crystalline forms are unpredictable and amorphous forms may offer different properties, affecting solubility and stability, which are crucial for pharmaceutical formulations and regulatory approval.

Innovation Solution

The development of novel crystalline forms of posiphen D-tartrate, specifically Form A and Form B, characterized by distinct X-ray powder diffraction patterns and high purity, which are prepared through specific methods and exhibit improved solubility and stability, enabling effective treatment and prevention of neurological disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If crystalline forms of posiphen D-tartrate are used, then purity and stability are improved, but solubility may be reduced

Engineering Contradiction:

ImprovestabilityVSAvoidsolubility

Core Design Contradiction:

Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by discovering and characterizing multiple crystalline polymorphic forms (Form A, Form B, and Form C) with different physical properties. By changing the crystalline structure parameters through controlled preparation methods, the patent achieves a balance between stability and solubility that enables effective pharmaceutical formulations.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If amorphous forms of posiphen D-tartrate are used, then solubility is improved, but stability and purity are reduced

Engineering Contradiction:

ImprovesolubilityVSAvoidstability

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent utilizes phase transitions by preparing amorphous forms through specific formulation methods and then controlling their transformation into crystalline polymorphic forms. This phase transition approach allows the patent to achieve both high solubility (from amorphous phase) and enhanced stability (from crystalline phase), resolving the contradiction between these properties.

Inventive Principle:

Principle #36Phase transitions

3Reliability

If novel crystalline forms are developed, then solubility and stability are improved, but formulation complexity increases

Engineering Contradiction:

ImprovereliabilityVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent manages formulation complexity by systematically characterizing multiple crystalline forms (Forms A, B, and C) with distinct physical parameters such as solubility, stability, and physical chemical properties. This parameter-based approach allows for reliable selection of the most suitable form for pharmaceutical development while providing a structured framework for formulation design.

Inventive Principle:

Principle #35Parameter changes

4Ease of manufacture

If crystalline forms are prepared through conventional methods, then manufacturing simplicity is maintained, but form predictability is lost

Engineering Contradiction:

Improveease of manufactureVSAvoidform predictability

Core Design Contradiction:

Ease of manufactureVSLoss of information

Solution Approach 1:

The patent applies preliminary action by establishing controlled preparation methods for each crystalline polymorphic form (Forms A, B, and C) before pharmaceutical development. These predetermined methods ensure reproducible formation of specific crystalline forms with predictable properties, eliminating the unpredictability of conventional preparation approaches while maintaining manufacturing feasibility.

Inventive Principle:

Principle #10Preliminary action

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

Form B demonstrates faster delivery and longer retention in the body, providing higher initial concentrations and prolonged effectiveness in treating neurodegenerative and neuropsychiatric disorders, with enhanced solubility and stability compared to Form A.

Implementation Method 1

characterized by distinct X-ray powder diffraction patterns

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Implementation Method 2

characterized by distinct X-ray powder diffraction patterns

Methodology Applied

Scientific EffectBragg diffraction: Bragg Diffraction

Data Source

PatentUS20260062418A1Solid forms of posiphen d-tartrate

Publication Date: 2026.03.05 ANNOVIS BIO INC

AI summary

Solid forms of (3aR)-1, 3a, 8-trimethyl-1, 2, 3, 3a, 8, 8a-hexahydropyrrolo (2, 3-b) indol-5-yl phenyl-carbamate tartrate, including crystalline (3aR)-1, 3a, 8-trimethyl-1, 2, 3, 3a, 8, 8a-hexahydropyrrolo (2, 3-b) indol-5-yl phenyl-carbamate tartrate (posiphen D-tartrate Form A), crystalline (3aR)-1, 3a, 8-trimethyl-1, 2, 3, 3a, 8, 8a-hexahydropyrrolo (2, 3-b) indol-5-yl phenyl-carbamate tartrate dihydrate (posiphen D-tartrate Form B), crystalline (3aR)-1, 3a, 8-trimethyl-1, 2, 3, 3a, 8, 8a-hexahydropyrrolo (2, 3-b) indol-5-yl phenyl-carbamate tartrate Form A having the peak of Pattern C (posiphen D-tartrate Form A+Pattern C), and amorphous (3aR)-1, 3a, 8-trimethyl-1, 2, 3, 3a, 8, 8a-hexahydropyrrolo (2, 3-b) indol-5-yl phenyl-carbamate tartrate, are disclosed. Pharmaceutical compositions comprising posiphen D-tartrate Form A, posiphen D-tartrate Form B, posiphen D-tartrate Form A having the peaks of Pattern C, and amorphous posiphen D-tartrate, and methods of treating various conditions by administering these solid forms, are also disclosed.