Amorphous Polymeric Drug Salts as Ionic Solid Dispersion Forms of Ciprofloxacin

Area of Science:

• Pharmaceutical Science
• Materials Science
• Drug Delivery

Background:

• Ciprofloxacin (CIP) exhibits poor aqueous solubility and permeability, limiting its therapeutic efficacy.
• Existing strategies like salt formation and metal complexes have had limited success in improving CIP's physicochemical properties.

Purpose of the Study:

• To prepare amorphous solid dispersions (ASDs) of ciprofloxacin (CIP) using various polymers via ball milling.
• To evaluate the solid-state characteristics, physical stability, solubility, permeability, and antimicrobial activity of the developed ASDs.

Main Methods:

• Amorphous solid dispersions (ASDs) were prepared by ball milling CIP with acidic polymers (Eudragit L100, Eudragit L100-55, Carbopol, HPMCAS).
• Solid-state properties (X-ray diffraction, DSC), physical stability (humidity, temperature), solubility (water, simulated intestinal fluid), permeability (PAMPA), and antimicrobial activity (MIC, MBC) were assessed.

Main Results:

• Acidic polymers facilitated CIP amorphization through the formation of amorphous polymeric drug salts via interactions between CIP's amine group and polymer carboxylates.
• ASDs exhibited enhanced solubility and maintained or improved drug permeability.
• While some crystallization occurred under accelerated conditions, ASDs remained X-ray amorphous at 90% RH/25 °C and showed improved antimicrobial activity (MIC/MBC) with specific HPMCAS formulations.

Conclusions:

• Amorphous solid dispersions (ASDs) are a viable approach to enhance the solubility, permeability, and antimicrobial activity of ciprofloxacin (CIP).
• The use of specific acidic polymers, particularly HPMCAS, in ASD formulations can lead to significant improvements in CIP's pharmaceutical and therapeutic properties.