Preformulation studies of levonorgestrel: A supplier variation analysis

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Development

Background:

• Levonorgestrel (LNG) is a critical synthetic progestogen used in various contraceptive formulations.
• Understanding LNG's solid-state properties and stability is crucial for consistent drug product performance.
• Variability in drug substance can impact manufacturing processes and final product efficacy.

Purpose of the Study:

• To assess variability in Levonorgestrel (LNG) drug substance concerning polymorphism and purity.
• To investigate the physical stability and hygroscopicity of LNG in different environments.
• To determine equilibrium solubility of LNG in various solvents and pharmaceutical vehicles.

Main Methods:

• Solid-state characterization using FTIR, Raman, NMR (solid and liquid-state), DSC, TGA, XRPD, WAXS, SAXS, and SEM.
• Dynamic vapor sorption (DVS) for hygroscopicity assessment.
• Solubility studies in organic solvents, dissolution media, and pharmaceutical vehicles.

Main Results:

• Comprehensive analysis revealed only minor thermal property variations among LNG samples from eleven suppliers.
• All analyzed LNG samples exhibited the same polymorphic form, indicating high consistency.
• LNG demonstrated high physical stability under elevated temperatures and across tested organic solvents.
• Equilibrium solubility data were successfully obtained for diverse relevant media.

Conclusions:

• Levonorgestrel drug substance exhibits high physical stability and consistent polymorphic form across different suppliers.
• The observed stability suggests a low risk of polymorphic transitions during pharmaceutical manufacturing.
• The obtained solubility data will aid in the development of novel LNG-containing dosage forms.