Hydrochloride salt co-crystals: preparation, characterization and physicochemical studies

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Modifying physicochemical properties of active pharmaceutical ingredients (APIs) is crucial for optimizing drug delivery and therapeutic efficacy.
• Fluoxetine hydrochloride (FH), an ionic salt, presents challenges in solubility and dissolution, impacting its bioavailability.
• Co-crystallization offers a promising strategy for tailoring the properties of existing drug substances without altering their core therapeutic activity.

Purpose of the Study:

• To investigate the impact of co-crystallization on the physicochemical properties of fluoxetine hydrochloride (FH).
• To explore the potential of various carboxylic acid co-formers in forming stable co-crystals with FH.
• To evaluate the solubility and dissolution profiles of the resulting FH co-crystals.

Main Methods:

• Co-crystallization screening of FH with carboxylic acid co-formers using the slow evaporation method.
• Characterization of co-crystals using photomicrography, melting point determination, FTIR, DSC, and PXRD.
• Assessment of aqueous solubility in various buffers and evaluation of powder and intrinsic dissolution profiles.

Main Results:

• Four novel co-crystals of FH were successfully synthesized: FH-maleic acid (FH-MA), FH-glutaric acid (FH-GA), FH-L-tartaric acid (FH-LTA), and FH-DL-tartaric acid (FH-DLTA).
• Co-crystals exhibited distinct crystal morphology, thermal behavior, spectroscopic signatures, and X-ray diffraction patterns compared to pure FH.
• The FH-MA co-crystal demonstrated significantly enhanced aqueous solubility and a higher dissolution rate in distilled water and buffer solutions compared to pure FH.

Conclusions:

• Co-crystallization is an effective approach for modifying the physicochemical properties of ionic APIs like fluoxetine hydrochloride.
• The FH-MA co-crystal shows superior solubility and dissolution characteristics, indicating potential for improved drug formulation.
• This strategy provides a viable pathway for enhancing the performance of existing ionic drugs through tailored solid-state modifications.