Solid-state characterization and dissolution properties of Fluvastatin sodium salt hydrates

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Drug Characterization

Background:

• Understanding the solid-state properties of pharmaceutical compounds is crucial for drug development and formulation.
• Fluvastatin sodium salt is a widely used cholesterol-lowering medication, necessitating well-defined crystalline forms.

Purpose of the Study:

• To investigate and compare the solid-state properties of Fluvastatin sodium salt crystallized from various solvents.
• To characterize different crystalline forms and their impact on dissolution rates.

Main Methods:

• X-ray powder diffractometry (XRPD)
• Differential scanning calorimetry (DSC)
• Thermogravimetry (TGA)
• Nuclear magnetic resonance (NMR) spectroscopy (liquid and solid-state)
• Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)
• Scanning electron microscopy (SEM)
• Intrinsic dissolution rate (IDR) testing

Main Results:

• Three distinct crystalline forms of Fluvastatin sodium salt were identified.
• Form I, found in the commercial raw material and Fluvastatin-Acetonitrile (ACN) samples, was characterized as a monohydrate with 4% water content.
• The United States Pharmacopeia (USP) reference standard was identified as Form II hydrate.
• An ethanol solvate was observed, presenting a mixture of phases.
• Crystalline form significantly influenced the intrinsic dissolution rate.

Conclusions:

• The study successfully elucidated the solid-state properties and polymorphic forms of Fluvastatin sodium salt.
• Identification of distinct crystalline forms (Form I monohydrate, Form II hydrate, ethanol solvate) is critical for quality control and formulation.
• Understanding the influence of crystalline form on dissolution rate is essential for predicting in vivo drug performance.