SN38 Crystalline Polymorph Stability via Solvent Control

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Solution Overview

Problem

There is a need for an improved form of 7-ethyl-10-hydroxycamptothecin (SN38) that is more suitable for pharmaceutical use, as existing crystalline forms may not provide optimal stability and efficacy.

Innovation Solution

A novel crystalline form of SN38 is produced through specific processes involving solvents like acetic acid, 1,2-dichloroethane, and other organic compounds, resulting in distinct X-ray diffraction and infrared spectra, and is incorporated with pharmaceutically acceptable carriers to form a stable pharmaceutical composition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing crystalline forms of SN38 are used, then the compound is available for pharmaceutical use, but stability and efficacy are not optimal

Engineering Contradiction:
ImprovestabilityVSAvoidsuitability for pharmaceutical use
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the crystallization conditions (solvent type, temperature, pH) to produce a novel crystalline polymorph of SN38 with improved stability characteristics. Specifically, the invention uses acetic acid as a solvent and controls crystallization at specific temperatures to obtain a crystalline form with enhanced pharmaceutical suitability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions by inducing crystallization from solution to form a specific polymorphic structure. The process involves dissolving SN38 in acetic acid and then controlling the phase transition during crystallization to produce the desired stable crystalline form with specific X-ray diffraction patterns.

Inventive Principle:
Principle #36Phase transitions

2Reliability

If a novel crystalline form is developed, then stability is enhanced, but the process complexity increases

Engineering Contradiction:
ImprovestabilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses acetic acid as an intermediary solvent to facilitate the crystallization process. This mediator enables the formation of the stable crystalline polymorph through a controlled crystallization process, simplifying what would otherwise be a complex phase transition procedure.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 novel crystalline form of SN38 exhibits enhanced stability and is suitable for pharmaceutical use, maintaining its form under controlled conditions, such as 25°C and 70% relative humidity for one year, with specific X-ray and infrared patterns confirming its identity and purity.

Implementation Method 1

the crystalline polymorph of SN38 exhibits an X-ray diffraction pattern having peaks at 10.9±0.2, 13.2±0.2, 23.9±0.2, and 26.1±0.2 2-theta degree

Methodology Applied
Scientific EffectX-ray diffraction: X-Ray

Implementation Method 2

the crystalline polymorph exhibits an infrared spectrum with bands at 3584±2 cm-1

Methodology Applied
Scientific EffectInfrared spectroscopy: Infrared Radiation

Data Source

PatentEP2170329B1Process for preparing a crystalline polymorph of 7-ethyl-10-hydroxycamptothecin
Publication Date: 2014.12.17 SCINOPHARM TAIWAN LTD
  • EP2170329B1 patent drawingFigure 1
  • EP2170329B1 patent drawingFigure 2
  • EP2170329B1 patent drawing

AI summary

A crystalline polymorph of 7-ethyl-10- hydroxycaraptothecin exhibiting an X-ray diffraction pattern having peaks at 10.9±0.2, 13.2±0.2, 23.910.2, and 26.110.2 2-theta degree.