Enhanced dissolution and antibacterial potential of cinacalcet hydrochloride via ternary solid dispersions.

Abstract

Cinacalcet hydrochloride (HCl), a calcium-sensing receptor agonist used to treat hyperparathyroidism, suffers from poor solubility, reducing its bioavailability. Recently, cinacalcet HCl has been probed for repurposing as antibacterial agent. This work investigates cinacalcet HCl's potential as an antibacterial agent and provides a formulation to improve the drug dissolution. Solid dispersion formulations using Poloxamer 407, with and without Soluplus^®, were prepared via solvent evaporation and hot melt congealing methods. The resulting formulations were analyzed using differential scanning calorimetry, FTIR spectroscopy, X-ray powder diffraction, and dissolution studies. These formulations significantly enhanced cinacalcet HCl dissolution compared to the unprocessed form, achieving up to a 15-fold increase in Q5 (percent of cinacalcet HCl dissolved after 5 min). The dissolution efficiency rose from 28% for the pure drug to 94.8 and 87.8% for formulations F6 and F7, respectively. Microbiological evaluations confirmed the antibacterial effect of cinacalcet HCl, which was notably increased in the Poloxamer 407 and Soluplus^® hybrid formulation (F7) with a MIC of 64-128 µg/ml. Antibiofilm activity was also observed, with qRT-PCR indicating downregulation of biofilm genes (icaA, icaD, and fnbA). This study introduces a cinacalcet HCl formulation prepared using a scalable, green approach, demonstrating significant potential for antimicrobial applications.