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Purpose <p>The limited aqueous solubility and poor bioavailability of aceclofenac, a widely prescribed non-steroidal anti-inflammatory drug (NSAID), pose significant formulation challenges. Paracetamol, often co-administered with aceclofenac, also suffers from formulation-related constraints. This study aimed to develop and characterize a novel 1:1 aceclofenac–paracetamol drug–drug cocrystal to overcome these limitations, using a mechanothermal synthesis approach. Molecular docking was employed to predict favourable intermolecular interactions and guide cocrystal design.</p> Methods <p>Molecular docking simulations revealed strong binding interactions between aceclofenac and paracetamol, including hydrogen bonding and π–π stacking, with a binding energy of − 2.4&#xa0;kcal/mol reflects a weak-to-moderate interaction; still relevant for supramolecular assembly. Cocrystal formation was achieved through cogrinding, microwave irradiation, and a combined mechanothermal method. The resulting solid forms were characterized using Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Physicochemical properties were evaluated through solubility, dissolution, and in vitro anti-inflammatory activity studies.</p> Results <p>The optimized formulation (Batch G), prepared using sequential cogrinding followed by microwave irradiation, showed significantly enhanced aqueous solubility of aceclofenac (14.50 ± 1.114&#xa0;µg/mL), improved dissolution rate (49.30 ± 0.24% at 120&#xa0;min), and potent anti-inflammatory activity (IC₅₀ = 89.96&#xa0;µg/mL). Structural characterization confirmed the formation of a stable and distinct cocrystalline phase.</p> Conclusion <p>This study demonstrates the effectiveness of integrating molecular modelling with microwave-assisted mechanochemistry for drug–drug cocrystal development. The aceclofenac–paracetamol cocrystal offers a promising strategy to enhance the biopharmaceutical performance of poorly soluble drugs. Further in vivo evaluation and scale-up studies are warranted.</p>

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“Cogrinding and Microwave-Assisted Cocrystallization of Aceclofenac–Paracetamol: A Dual Approach for the Modification of Physicochemical Properties”

  • 期刊论文

  • 发表日期：

    2025年10月1日

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  • Ankita Patil,
  • Sujata Jadhav,
  • Amol Shete,
  • Swapnil Patil

摘要

Purpose

The limited aqueous solubility and poor bioavailability of aceclofenac, a widely prescribed non-steroidal anti-inflammatory drug (NSAID), pose significant formulation challenges. Paracetamol, often co-administered with aceclofenac, also suffers from formulation-related constraints. This study aimed to develop and characterize a novel 1:1 aceclofenac–paracetamol drug–drug cocrystal to overcome these limitations, using a mechanothermal synthesis approach. Molecular docking was employed to predict favourable intermolecular interactions and guide cocrystal design.

Methods

Molecular docking simulations revealed strong binding interactions between aceclofenac and paracetamol, including hydrogen bonding and π–π stacking, with a binding energy of − 2.4 kcal/mol reflects a weak-to-moderate interaction; still relevant for supramolecular assembly. Cocrystal formation was achieved through cogrinding, microwave irradiation, and a combined mechanothermal method. The resulting solid forms were characterized using Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Physicochemical properties were evaluated through solubility, dissolution, and in vitro anti-inflammatory activity studies.

Results

The optimized formulation (Batch G), prepared using sequential cogrinding followed by microwave irradiation, showed significantly enhanced aqueous solubility of aceclofenac (14.50 ± 1.114 µg/mL), improved dissolution rate (49.30 ± 0.24% at 120 min), and potent anti-inflammatory activity (IC₅₀ = 89.96 µg/mL). Structural characterization confirmed the formation of a stable and distinct cocrystalline phase.

Conclusion

This study demonstrates the effectiveness of integrating molecular modelling with microwave-assisted mechanochemistry for drug–drug cocrystal development. The aceclofenac–paracetamol cocrystal offers a promising strategy to enhance the biopharmaceutical performance of poorly soluble drugs. Further in vivo evaluation and scale-up studies are warranted.