Eutectic Formation of Naproxen with Some Dicarboxylic Acids

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Eutectic formation with additives is a key strategy to enhance the dissolution of active pharmaceutical ingredients (APIs).
• This improvement stems from increased surface area due to finely divided micro-domains formed during phase separation upon solidification.
• Naproxen (NPX) is a Class II API with poor solubility, necessitating formulation strategies for improved oral delivery.

Purpose of the Study:

• To identify suitable eutectic-forming additives for naproxen (NPX).
• To develop a practical eutectic mixture of NPX with at least 20 wt% additive for oral delivery.
• To investigate the dissolution enhancement of NPX-based eutectic mixtures.

Main Methods:

• Screening of potential additives based on solubility parameter proximity.
• Construction of binary melting diagrams to determine eutectic compositions.
• Characterization of melt-crystallized eutectics and assessment of dissolution rates at pH 5.0.

Main Results:

• Dicarboxylic acids (succinic, glutaric, and suberic acids) were identified as promising additives for NPX.
• A eutectic mixture of NPX with suberic acid (55 wt% NPX) was successfully developed.
• Melt-crystallized eutectics exhibited significantly enhanced dissolution compared to physical mixtures and neat NPX, attributed to observed lamellar structures.

Conclusions:

• Dicarboxylic acids are effective eutectic-forming additives for naproxen.
• Eutectic mixtures offer a viable strategy to improve the dissolution of naproxen.
• The findings support systematic development of API-eutectic mixtures for enhanced oral bioavailability.