Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
39875032
DOI
10.1016/j.ijpharm.2025.125279
PII: S0378-5173(25)00115-2
Knihovny.cz E-resources
- Keywords
- Cancer treatment(s), Deep eutectic solvent(s), Enabling formulation(s), Eutectic mixture(s), Novel pharmaceutic(s), Therapeutic deep eutectic solvent(s),
- MeSH
- Abiraterone Acetate * chemistry administration & dosage MeSH
- Drug Combinations MeSH
- Ibuprofen * chemistry administration & dosage MeSH
- Caprylates chemistry MeSH
- Decanoic Acids chemistry MeSH
- Lauric Acids chemistry MeSH
- Antineoplastic Agents * chemistry administration & dosage MeSH
- Solvents * chemistry MeSH
- Solubility MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Abiraterone Acetate * MeSH
- decanoic acid MeSH Browser
- Drug Combinations MeSH
- Ibuprofen * MeSH
- Caprylates MeSH
- Decanoic Acids MeSH
- Lauric Acids MeSH
- lauric acid MeSH Browser
- octanoic acid MeSH Browser
- Antineoplastic Agents * MeSH
- Solvents * MeSH
In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.
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