Determination of the nateglinide polymorphic purity through DSC

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Controlling drug crystallization to ensure the desired polymorph is critical in preformulation studies.
• Nateglinide exists in different polymorphic forms (H and B) that can impact drug efficacy and stability.
• Accurate quantification of polymorphic mixtures is essential for quality control in pharmaceutical manufacturing.

Purpose of the Study:

• To develop a reliable method for quantifying the polymorphic purity of nateglinide in binary mixtures of polymorphs H and B.
• To investigate the influence of sample preparation methods on nateglinide polymorphic transitions.
• To establish a quantitative analysis based on differential scanning calorimetry (DSC) data.

Main Methods:

• Preparation of binary mixtures of nateglinide polymorphs H and B with known compositions.
• Analysis of polymorphic mixtures using differential scanning calorimetry (DSC) to record melting peaks.
• Evaluation of sample preparation techniques, specifically grinding and heating, for their effect on polymorphic transitions.

Main Results:

• Grinding nateglinide samples induced a transition from the B to the H polymorph.
• Heating the binary mixtures also led to an enrichment of the H polymorph.
• A method was successfully developed to quantify the H polymorph content in mixtures with the B form using the melting peak of the B polymorph, without grinding.

Conclusions:

• The method of sample preparation significantly influences nateglinide polymorphic composition.
• Differential scanning calorimetry (DSC) can be effectively utilized to quantify nateglinide polymorphic purity.
• The developed method provides a crucial tool for ensuring the correct polymorphic form in nateglinide drug formulations.