Ziprasidone Sulfate Polymorphs for Solubility

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Solution Overview

Problem

Current methods for preparing Ziprasidone salts, such as hydrochloride and hydrogensulfate, face challenges in achieving optimal solubility and bioavailability, leading to suboptimal pharmaceutical formulations.

Innovation Solution

Development of novel polymorphic forms of Ziprasidone sulfates with controlled crystal water content and particle size, specifically Ziprasidone sulfate and hydrogensulfate, which exhibit improved solubility and stability, enabling better bioavailability and tolerance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional concentration and recrystallization techniques are employed to prepare Ziprasidone salts, then the salts can be obtained in high purity, but the solubility and bioavailability remain suboptimal

Engineering Contradiction:
ImprovepurityVSAvoidsolubility
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent changes the crystal structure parameters by controlling the formation of specific polymorphic forms (monohydrate and anhydrous forms) through controlled crystallization conditions, thereby improving solubility while maintaining high purity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions during crystallization to obtain specific polymorphic forms with optimized solubility properties, transitioning from solution to solid state in a controlled manner to achieve desired crystal structure

Inventive Principle:
Principle #36Phase transitions

2Ease of manufacture

If conventional methods are used to prepare Ziprasidone salts, then the preparation process is simple, but the particle size is large resulting in reduced bioavailability

Engineering Contradiction:
Improveprocess simplicityVSAvoidbioavailability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent segments the crystallization process into controlled stages, producing fine particles through controlled nucleation and growth, thereby increasing surface area and bioavailability while maintaining process simplicity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from conventional bulk crystallization to controlled fine particle formation, effectively changing the particle size dimension to optimize bioavailability without complicating the overall manufacturing process

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Stability of the object's composition

If existing Ziprasidone salts are used, then the formulations are stable, but the solubility is insufficient leading to suboptimal therapeutic effectiveness

Engineering Contradiction:
ImprovestabilityVSAvoidsolubility
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent modifies the crystal structure parameters by forming specific polymorphic forms with optimized water content, achieving both stability and enhanced solubility simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite crystal structures (monohydrate and anhydrous forms) that combine stability and solubility properties, achieving superior performance compared to conventional salts

Inventive Principle:
Principle #40Composite materials

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 polymorphic forms of Ziprasidone sulfates demonstrate enhanced solubility and bioavailability, allowing for reduced drug dosages while maintaining or improving therapeutic effectiveness, thus addressing the limitations of existing formulations.

Implementation Method 1

The present invention relates to novel polymorphic forms of Ziprasidone sulfates... The present Ziprasidone sulfates may be obtained in high purity, have good stability and advantageous formulation properties

Methodology Applied
Scientific EffectPolymorphism:

Implementation Method 2

Ziprasidone sulfates, i.e. Ziprasidone sulfate and Ziprasidone hydrogensulfate, having specific amounts of crystal water... The solubility of the compounds is on the one hand directly influenced by the content of crystal water

Methodology Applied
Scientific EffectHydration: Hydrates

Implementation Method 3

The present Ziprasidone sulfates... are characterized by small average particle sizes... The solubility of the compounds is on the other hand by the low particle size

Methodology Applied
Scientific EffectParticle size reduction:

Data Source

PatentEP2046786B1Polymorphic forms of ziprasidone sulfates
Publication Date: 2017.12.27 KRKA
  • EP2046786B1 patent drawingFigure 1(a)
  • EP2046786B1 patent drawingFigure 1(b)
  • EP2046786B1 patent drawingFigure 1(c)

AI summary

The present invention relates to novel polymorphic forms of Ziprasidone sulfates Ziprasidone Hn+ X Z H2O wherein Ziprasidone is a compound of the formula; H is hydrogen; n is 1 or 2; 2- X is HSO4 - or SO4 2 -; and Z is O to 30., as well as to a process for their preparation and pharmaceutical formulations containing it. The present polymorphic forms of Ziprasidone sulfates are characterized by small average particle sizes and high solubility bestowing the compounds an improved bioavailability.