Solid-state characterization and dissolution properties of naproxen-arginine-hydroxypropyl-beta-cyclodextrin ternary...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Physical Pharmacy

Background:

• Naproxen is a poorly water-soluble anti-inflammatory drug.
• Improving the dissolution properties of poorly soluble drugs is crucial for enhancing bioavailability.
• Cyclodextrins and amino acids are known excipients for drug solubility enhancement.

Purpose of the Study:

• To investigate the effect of ternary complexation of naproxen with hydroxypropyl-beta-cyclodextrin and L-arginine on its dissolution properties.
• To compare the efficacy of binary and ternary systems in improving naproxen dissolution.
• To elucidate the interactions between naproxen, hydroxypropyl-beta-cyclodextrin, and L-arginine.

Main Methods:

• Preparation of binary (drug-cyclodextrin, drug-arginine) and ternary (drug-cyclodextrin-arginine) systems using blending, cogrinding, and coevaporation.
• Characterization of systems using differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, and X-ray diffractometry.
• Evaluation of dissolution behavior using a continuous flow through method.

Main Results:

• Solid-state studies confirmed strong interactions and amorphous nature in ternary coevaporated and coground systems.
• All ternary combinations significantly improved naproxen dissolution rate compared to binary systems (P<0.001).
• The ternary coevaporate exhibited the highest improvement, with a 15-fold increase in relative dissolution rate and dissolution efficiency.

Conclusions:

• Ternary complexation of naproxen with hydroxypropyl-beta-cyclodextrin and L-arginine synergistically enhances dissolution.
• The observed enhancement is attributed to combined inclusion complexation and salt formation, with a specific role for arginine.
• The ternary coevaporate represents a highly effective formulation strategy for improving naproxen dissolution properties.