Anhydrous Saxagliptin Hydrochloride Crystalline Forms

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The existing polymorphic forms of Saxagliptin hydrochloride have high water content, leading to decreased chemical stability and poor processing behavior, which complicates the formulation of pharmaceutical compositions.

Innovation Solution

Development of anhydrous forms of Saxagliptin hydrochloride, specifically Form I-S, Form HT-S, Form HT-IV-S, and Form IV-S, characterized by distinct x-ray powder diffraction and infrared spectra, which are prepared through crystallization and drying processes to maintain low water content (<1.5% w/w), enhancing chemical stability and processing ease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If hydrated polymorphic forms of Saxagliptin hydrochloride are used, then the compound can be obtained in crystalline form, but the water content is high leading to decreased chemical stability and poor processing behavior

Engineering Contradiction:

Improvechemical stabilityVSAvoidwater content

Core Design Contradiction:

Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent changes the physical state parameter from hydrated to anhydrous form by controlling crystallization conditions and storage environment. The anhydrous forms are obtained by crystallizing from organic solvents and storing under controlled humidity conditions, transforming the water content parameter from high (hydrated forms) to low (<1.5% w/w), thereby improving chemical stability while maintaining crystalline structure

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transition processes including crystallization from organic solvents and dehydration transitions to convert hydrated forms into anhydrous forms. The transformation involves removing water molecules from the crystal structure through controlled drying and storage, achieving a phase change that improves stability without compromising the crystalline nature of the compound

Inventive Principle:

Principle #36Phase transitions

2Ease of manufacture

If hydrated forms of Saxagliptin hydrochloride are used, then crystalline structure is achieved, but processing behavior is poor due to clogging and sticking

Engineering Contradiction:

Improveprocessing behaviorVSAvoidwater content

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the moisture content parameter from high (hydrated forms with significant water content) to low (anhydrous forms with <1.5% w/w water content). This parameter change fundamentally improves processing behavior by eliminating clogging and sticking issues associated with high water content, while maintaining the crystalline structure necessary for manufacturing

Inventive Principle:

Principle #35Parameter changes

3Reliability

If anhydrous forms of Saxagliptin hydrochloride are developed, then chemical stability and processing behavior are improved, but new crystal forms with distinct physical properties must be identified and characterized

Engineering Contradiction:

Improvepredictability of solubility profileVSAvoidcharacterization complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs X-ray diffraction technology to characterize the crystal structures of anhydrous forms, replacing manual identification methods with automated diffraction analysis. This substitution enables systematic identification and characterization of multiple anhydrous polymorphic forms (Form I-S, Form HT-S, Form HT-IV-S, Form IV-S) with distinct physical properties, providing predictable solubility profiles while managing characterization complexity through standardized analytical procedures

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 anhydrous forms exhibit improved chemical stability and dissolution rates, reducing the risk of clogging and sticking issues, and can be formulated into stable pharmaceutical compositions with predictable solubility profiles, suitable for treating diabetes and related diseases.

Implementation Method 1

crystallization and drying processes to maintain low water content (<1.5% w/w)

Methodology Applied

Scientific EffectCrystallization: Crystallisation

Implementation Method 2

crystallization and drying processes to maintain low water content (<1.5% w/w)

Methodology Applied

Scientific EffectEvaporation: Evaporation

Implementation Method 3

characterized by distinct x-ray powder diffraction and infrared spectra

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Implementation Method 4

characterized by distinct x-ray powder diffraction and infrared spectra

Methodology Applied

Scientific EffectInfrared absorption: Absorption (EM radiation)

Data Source

PatentUS9260389B2Crystal forms of saxagliptin

Publication Date: 2016.02.16 SANDOZ LTD

AI summary

The present invention relates to novel polymorphic forms of Saxagliptin Hydrochloride. The present invention also relates to methods of making polymorphic forms of Saxagliptin Hydrochloride.