LSD1 Inhibitor Formulation Stability via Organic Acid Mediation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current LSD1 inhibitors face challenges in stability and efficacy, particularly in maintaining their potency over time due to degradation issues, which affects their effectiveness in treating LSD1-mediated cancers.

Innovation Solution

The development of a pharmaceutical formulation comprising Compound 1 di-tosylate salt, an organic acid like fumaric acid, and a diluent such as lactose, which enhances stability and reduces degradation, forming a solid oral dosage form that inhibits LSD1 activity effectively.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If LSD1 inhibitors are formulated without organic acid and diluent, then the formulation is simple, but the stability and bioavailability of the compound deteriorates

Engineering Contradiction:
Improvestability of Compound 1 di-tosylate saltVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent introduces organic acid (such as fumaric acid) and diluent (such as lactose) as intermediary substances that mediate between the active ingredient and the environment. These intermediaries protect the compound from degradation while maintaining formulation simplicity through well-established pharmaceutical excipients.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The formulation combines multiple materials (Compound 1 di-tosylate salt, organic acid, and diluent) into a composite pharmaceutical composition. This composite structure enhances the stability and bioavailability of the active ingredient while managing its degradation issues through synergistic interactions between components.

Inventive Principle:
Principle #40Composite materials

2Duration of action of stationary object

If LSD1 inhibitors are stored without protective formulation, then storage is simple, but degradation increases over time

Engineering Contradiction:
Improveduration of efficacy over timeVSAvoidease of formulation preparation
Core Design Contradiction:
Duration of action of stationary objectVSEase of manufacture

Solution Approach 1:

The patent applies preliminary protective action by incorporating organic acid and diluent into the formulation before storage. This pre-protection prevents degradation during storage, extending the duration of efficacy without requiring complex manufacturing processes, as these are standard pharmaceutical excipients.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If the compound is administered without formulation optimization, then administration is simple, but bioavailability and therapeutic efficacy are reduced

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidformulation structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the physical and chemical parameters of the compound by forming it into a formulated composition with organic acid and diluent. This parameter change improves bioavailability and therapeutic efficacy by protecting the compound from degradation and enhancing its delivery, while the formulation structure remains relatively simple using standard excipients.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3445339B1Formulations of an LSD1 inhibitor
Publication Date: 2023.08.23 INCYTE CORP
  • EP3445339B1 patent drawingFigure 1
  • EP3445339B1 patent drawingFigure 2
  • EP3445339B1 patent drawingFigure 3

AI summary

The present application relates to pharmaceutical formulations and dosage forms of a lysine specific demethylase-1 (LSD1) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, including methods of preparation thereof, which are useful in the treatment of LSD1 mediated diseases such as cancer.