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Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents.

Shaida Panbachi1, Josef Beranek2, Martin Kuentz3

  • 1University of Basel, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, 4056 Basel, Switzerland; Zentiva, k.s., U Kabelovny 130, 102 00 Praha 10, Czech Republic; University of Applied Sciences and Arts Northwest. Switzerland, School of Life Sciences, Institute of Pharma Technology, Hofackerstr. 30, CH-4132 Muttenz, Switzerland.

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Summary

This study developed novel drug-based therapeutic deep eutectic solvents (THEDESs) using ibuprofen to enhance the solubility of abiraterone acetate for fixed-dose combination anticancer therapies.

Keywords:
Cancer treatment(s)Deep eutectic solvent(s)Enabling formulation(s)Eutectic mixture(s)Novel pharmaceutic(s)Therapeutic deep eutectic solvent(s)

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Computational Chemistry

Background:

  • Poorly soluble drugs present formulation challenges for oral delivery.
  • Deep eutectic solvents (DESs) show promise for enhancing drug solubility.
  • Therapeutic DESs (THEDESs) offer a dual-action approach by combining therapeutic agents.

Purpose of the Study:

  • To explore the potential of ibuprofen (IBU)-based therapeutic deep eutectic solvents (THEDESs) for solubilizing abiraterone acetate (AbAc).
  • To create fixed-dose combination formulations of IBU and AbAc with enhanced solubility and dissolution.
  • To investigate the influence of fatty acid chain length on the solubilization capacity of IBU-based THEDESs.

Main Methods:

  • Preparation and characterization of four IBU-based THEDESs with varying fatty acids (octanoic, nonanoic, decanoic, dodecanoic acid).
  • Quantum chemistry calculations to determine surface charge densities of fatty acids.
  • In vitro dissolution studies of AbAc and IBU from the developed THEDES formulations, with and without Tween 80.

Main Results:

  • IBU-based THEDESs demonstrated significant solubilization of AbAc, with maximum dissolution up to 1311.0 ± 125.4 mg/g in IBU:OctA.
  • In vitro dissolution showed simultaneous release of IBU and AbAc, with enhanced percentages upon addition of Tween 80.
  • Fatty acid chain length influenced AbAc solubilization, with shorter chains showing higher capacity.

Conclusions:

  • Drug-based THEDESs are effective for solubilizing poorly soluble drugs like AbAc.
  • IBU-based THEDESs offer a viable strategy for developing fixed-dose combination oral formulations.
  • These findings highlight the potential of THEDESs in drug delivery and combination therapy.