Formulation strategy of nitrofurantoin: co-crystal or solid dispersion?

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Poor drug solubility and bioavailability, like that of nitrofurantoin (NF), are linked to microscopic structural properties.
• Nitrofurantoin, a Biopharmaceutics Classification System class II drug, exhibits low water solubility and plasma concentrations, limiting its therapeutic efficacy.

Purpose of the Study:

• To compare the formulation strategies of co-crystallization and solid dispersion (SD) for improving nitrofurantoin's therapeutic efficacy.
• To evaluate the impact of these formulations on nitrofurantoin's solubility and dissolution characteristics.

Main Methods:

• Co-crystal preparation using NF and citric acid (1:1 ratio).
• Solid dispersion (SD) preparation with 30% NF and 70% hydroxypropyl methylcellulose (HPMC).
• Characterization using DSC, ATR-FTIR, microscopy, solubility, and dissolution studies.

Main Results:

• ATR-FTIR confirmed co-crystal formation and hydrogen bonding in solvent-evaporated and spray-dried SD systems.
• Co-crystals demonstrated a higher initial dissolution rate compared to SD formulations.
• Microscopic analysis and DSC provided insights into the structural changes and phase behavior.

Conclusions:

• Co-crystallization is a more effective approach than solid dispersion for enhancing nitrofurantoin dissolution.
• The study provides valuable insights into optimizing drug delivery systems for poorly soluble compounds.