Life sciences · Journal article

Drug−Drug Salts of Rucaparib with Nonsteroidal Anti-Inflammatory Drugs: Crystal Structures, Intermolecular Interactions, Solubility Enhancement, and Antitumor Activity

Crystal Growth & Design · September 8, 2026

Preliminary Why this matters to you Expert discussion

Early or partial results. Treat as a signal, not a conclusion.

AI Summary

This preclinical study reports successful synthesis and characterisation of three drug–drug salt formulations of rucaparib with NSAIDs, with improved aqueous solubility and in vitro cytotoxicity in bladder cancer cells. The work is physicochemical and mechanistic; no in vivo efficacy, tolerability, or clinical data are presented.

What was studied

Preclinical physicochemical characterisation and in vitro cytotoxicity study. J82 bladder cancer cells in vitro; no human subjects or animals.. Intervention: Three drug–drug salt formulations: rucaparib–flurbiprofen (RUCA-FLU), rucaparib–ibuprofen (RUCA-IBU), and rucaparib–naproxen (RUCA-NAP).. Compared with: Free rucaparib (parent compound)..

Key findings

RUCA-NAP showed 2.78-fold increased solubility of rucaparib compared to free rucaparib RUCA-NAP showed 1.66-fold increased cumulative dissolution percentage compared to free rucaparib in water RUCA-FLU displayed 3.38-fold stronger cytotoxicity than free rucaparib against J82 bladder cancer cells

Safety

In vitro cytotoxicity only; no in vivo tumour model, pharmacokinetics, or efficacy data reported. No tolerability, safety, or toxicity data for the salt forms in any system.

Who this may help

This formulation work is exploratory and demonstrates potential for improved drug delivery but requires preclinical pharmacokinetic and pharmacodynamic studies, toxicology assessment, and eventual clinical trials before any change to rucaparib therapy in cancer patients.

Plain-language summary

This is a preclinical physicochemical and in vitro study demonstrating salt formulation and cell-based cytotoxicity; it lacks in vivo efficacy data, clinical trials, or human studies needed to inform clinical practice.

Study design

As stated by the source record.

MethodsThree drug–drug salts were synthesized by acid–base proton transfer between rucaparib and three NSAIDs (flurbiprofen, ibuprofen, naproxen). Solid-state properties were characterised by X-ray diffraction, thermal analysis, FT-IR, 1H NMR, Hirshfeld surface analysis, and molecular modelling. Aqueous solubility and dissolution were measured. In vitro cytotoxicity was assessed against J82 bladder cancer cells. Stability was evaluated over 8 weeks.

DesignPreclinical physicochemical characterisation and in vitro cytotoxicity study

PopulationJ82 bladder cancer cells in vitro; no human subjects or animals.

InterventionThree drug–drug salt formulations: rucaparib–flurbiprofen (RUCA-FLU), rucaparib–ibuprofen (RUCA-IBU), and rucaparib–naproxen (RUCA-NAP).

ComparatorFree rucaparib (parent compound).

Reported figures

Quoted from the source exactly as published.

Solubility enhancement (RUCA-NAP)2.78-fold

Cumulative dissolution enhancement (RUCA-NAP)1.66-fold

Cytotoxicity enhancement RUCA-FLU3.38-fold

Cytotoxicity enhancement RUCA-NAP1.95-fold

Long-term stability duration8 weeks

Clinical bottom line

Caveats

In vitro cytotoxicity only; no in vivo tumour model, pharmacokinetics, or efficacy data reported.
No tolerability, safety, or toxicity data for the salt forms in any system.
No statistical analysis, confidence intervals, or p-values reported for cytotoxicity comparisons.
Single bladder cancer cell line used; generalisability to other cancer types or clinical outcomes unknown.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

limited

Uncontrolled, in vitro cytotoxicity assay only; no in vivo model or clinical data.

Directness

limited

Cell-line cytotoxicity is surrogate; does not address clinical efficacy or patient outcomes.

Consistency

insufficient

Single study; no comparison with prior data or replication reported.

Risk of bias

insufficient

No blinding, randomisation, or control group structure disclosed; preclinical work.

Sample adequacy

insufficient

No sample size reporting, statistical power, or replication within study disclosed.

Source abstract

Abstract Rucaparib (RUCA) is an orally administered PARP inhibitor with an important clinical value in cancer therapy, but its poor aqueous solubility remains a major challenge for improving its dissolution behavior and pharmaceutical performance. In this study, drug−drug salt formation was adopted to improve the physicochemical properties of RUCA by selecting three nonsteroidal anti-inflammatory drugs, namely, flurbiprofen (FLU), ibuprofen (IBU), and naproxen (NAP), as salt-forming components. Three salts (RUCA-FLU, RUCA-IBU, and RUCA-NAP) were successfully obtained, and their structures and solid-state properties were systematically characterized by X-ray diffraction analysis, thermal analysis, FT-IR, 1H NMR, Hirshfeld surface analysis, independent gradient model based on Hirshfeld partition (IGMH) analysis, molecular electrostatic potential, and HOMO−LUMO. Structural results confirmed that three salts were formed through acid−base proton transfer with lattice stabilization arising from multiple N−H···O hydrogen-bonding interactions. Among them, RUCA-NAP showed the best overall performance, exhibiting a RUCA solubility 2.78-fold that of free RUCA and a cumulative dissolution percentage 1.66-fold that of free RUCA in water. All salts exhibited acceptable solid-state stability during the 8 week long-term stability study. In vitro antitumor assays against J82 bladder cancer cells showed that RUCA-FLU and RUCA-NAP displayed 3.38-fold and 1.95-fold stronger cytotoxicity than that of RUCA, respectively. Overall, this work demonstrates that drug−drug salt formation is a robust approach for modulating the solid-state properties, dissolution behavior, and biological performance of RUCA.

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Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Tao ZhuangWenjing GaoShuo LiuJie DingJiyang ZhangCan Wang