The characterization and comparison of spray-dried mannitol samples

Area of Science:

• Pharmaceutical Science
• Materials Science
• Chemical Engineering

Background:

• Characterization of spray-dried mannitol powder is essential for pharmaceutical applications.
• Mannitol's polymorphic behavior significantly impacts drug product stability and regulatory compliance.
• Uncontrolled polymorphic transitions can lead to costly product recalls.

Purpose of the Study:

• To characterize the polymorphic content of commercial and laboratory-produced spray-dried mannitol.
• To investigate the polymorphic behavior of mannitol during pharmaceutical processing.
• To establish the implications of mannitol's polymorphic transitions on drug formulation.

Main Methods:

• Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and isothermal microcalorimetry (IMC) for thermal analysis.
• X-ray powder diffraction (XRPD) and Fourier transform Raman spectroscopy (FT-Raman) for structural analysis.
• Characterization of both commercial and lab-scale processed spray-dried mannitol.

Main Results:

• Commercial spray-dried mannitol samples contained alpha- and beta-polymorphic forms, with some exhibiting mixtures.
• Reprocessing via spray drying induced polymorphic transitions from alpha- to beta-mannitol in certain samples.
• The study confirmed the dynamic nature of mannitol's crystalline structure under processing conditions.

Conclusions:

• Mannitol's polymorphic behavior must be thoroughly evaluated during preformulation studies.
• Understanding and controlling polymorphic transitions are critical for ensuring consistent drug product quality.
• Polymorphic characterization throughout the supply chain, processing, and storage is vital for pharmaceutical development.