Romidepsin Formulation Mannitol Solubility Stability

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Solution Overview

Problem

Current cancer treatments are inadequate in addressing the ongoing public health challenge of cancer, with a need for effective therapies that can target various types of cancer, including hematological malignancies and solid tumors, and existing formulations of romidepsin may not provide optimal delivery or efficacy.

Innovation Solution

A romidepsin formulation incorporating mannitol as a diluent, which improves the solubility and stability of the drug, allowing for effective treatment of proliferative diseases such as carcinomas, sarcomas, leukemias, and lymphomas, by enhancing its therapeutic delivery and bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If romidepsin is formulated without optimal excipients, then the formulation is simpler, but the solubility and stability of the drug are reduced

Engineering Contradiction:
Improvedrug stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

Mannitol is introduced as an intermediary substance (excipient) that mediates between the drug romidepsin and the formulation system. The mannitol provides solubility enhancement and stability improvement without directly altering the drug molecule, acting as a bridge that enables effective drug delivery while maintaining formulation simplicity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The formulation utilizes parameter changes by selecting mannitol with specific physical and chemical properties (solubility, stability profile, compatibility) to optimize the drug delivery system. By changing the excipient parameters rather than the drug parameters, the formulation achieves improved solubility and stability while keeping the drug structure intact

Inventive Principle:
Principle #35Parameter changes

2Reliability

If existing romidepsin formulations are used, then the formulation is simpler, but the therapeutic delivery and bioavailability are not optimized

Engineering Contradiction:
Improvetherapeutic deliveryVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Mannitol serves as a mediator that enhances therapeutic delivery by improving drug solubility and stability in the formulation. This intermediary substance enables more reliable and consistent drug delivery to the patient without requiring complex delivery mechanisms or multiple components

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

By changing the excipient parameters (selecting mannitol with optimal solubility and stability characteristics), the formulation achieves improved therapeutic delivery and bioavailability. This parameter optimization approach enhances reliability without proportionally increasing formulation complexity

Inventive Principle:
Principle #35Parameter changes

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 romidepsin formulation with mannitol demonstrates improved solubility and stability, leading to enhanced therapeutic benefits in treating cancer, including hematological malignancies and solid tumors, by ensuring effective delivery and bioavailability of the active ingredient.

Implementation Method 1

A romidepsin formulation incorporating mannitol as a diluent, which improves the solubility and stability of the drug

Methodology Applied
Scientific EffectSolubility enhancement: Solvation

Implementation Method 2

A romidepsin formulation incorporating mannitol as a diluent, which improves the solubility and stability of the drug

Methodology Applied
Scientific EffectStability enhancement: Preservative

Data Source

PatentEP2802340B1Romidepsin formulations and uses thereof
Publication Date: 2020.10.28 CELGENE CORP
  • EP2802340B1 patent drawingFigure 1
  • EP2802340B1 patent drawingFigure 2A~2B
  • EP2802340B1 patent drawing

AI summary

Provided herein are formulations of romidepsin. Also provided are methods for producing these formulations and uses thereof. In one embodiment, the formulation is a combination of romidepsin and mannitol.