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<p>Co-amorphous systems have emerged as an advanced strategy to enhance the apparent solubility of poorly soluble drugs. This strategy offers the benefit of addressing stability challenges that often hinder conventional amorphous formulations. Although fenofibrate can be readily converted to its amorphous form, it exhibits considerable instability in this state. The manuscript assesses the antiplasticising effects of indomethacin and terfenadine within co-amorphous systems through the <i>in situ</i> preparation and characterisation of binary and ternary mixtures using Differential Scanning Calorimetry. The glass transition temperatures (<i>T</i><sub>g</sub>) of these systems were predicted using the Gordon–Taylor equation, and deviations from the model were evaluated to elucidate the characteristics governing co-amorphous behaviour. Among the binary systems, the 1:1 molar ratio terfenadine–indomethacin system exhibited the strongest positive interaction, with the highest <i>T</i><sub>g</sub> at 72.2&#xa0;°C, presenting a promising co-amorphous system to incorporate fenofibrate. Ternary mixtures with a higher molar proportion of terfenadine and a lower molar proportion of fenofibrate exhibited positive deviations, which were attributed to favourable molecular interactions between terfenadine and indomethacin. Conversely, ternary mixtures with a high molar proportion of fenofibrate demonstrated negative deviations, indicating non-ideal mixing behaviour. The Gordon–Taylor model of the ternary systems underestimated the plasticising effect of amorphous fenofibrate at higher proportions, leading to lower experimental <i>T</i><sub>g</sub>. Consequently, the system exhibits greater molecular mobility than expected, resulting in lower physical stability of CAMs. This finding highlights the importance of experimental data that signifies the lack of Gordon–Taylor model for predicting the plasticising influence of amorphous fenofibrate, leading to less stable CAMs.</p>

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Understanding the interactions between terfenadine, indomethacin and fenofibrate in Co-Amorphous systems by comparing the experimental data with prediction models

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Shifaa Alabrash,
  • Max F. Green,
  • Daniela Carta,
  • Milan D. Antonijevic

摘要

Co-amorphous systems have emerged as an advanced strategy to enhance the apparent solubility of poorly soluble drugs. This strategy offers the benefit of addressing stability challenges that often hinder conventional amorphous formulations. Although fenofibrate can be readily converted to its amorphous form, it exhibits considerable instability in this state. The manuscript assesses the antiplasticising effects of indomethacin and terfenadine within co-amorphous systems through the in situ preparation and characterisation of binary and ternary mixtures using Differential Scanning Calorimetry. The glass transition temperatures (Tg) of these systems were predicted using the Gordon–Taylor equation, and deviations from the model were evaluated to elucidate the characteristics governing co-amorphous behaviour. Among the binary systems, the 1:1 molar ratio terfenadine–indomethacin system exhibited the strongest positive interaction, with the highest Tg at 72.2 °C, presenting a promising co-amorphous system to incorporate fenofibrate. Ternary mixtures with a higher molar proportion of terfenadine and a lower molar proportion of fenofibrate exhibited positive deviations, which were attributed to favourable molecular interactions between terfenadine and indomethacin. Conversely, ternary mixtures with a high molar proportion of fenofibrate demonstrated negative deviations, indicating non-ideal mixing behaviour. The Gordon–Taylor model of the ternary systems underestimated the plasticising effect of amorphous fenofibrate at higher proportions, leading to lower experimental Tg. Consequently, the system exhibits greater molecular mobility than expected, resulting in lower physical stability of CAMs. This finding highlights the importance of experimental data that signifies the lack of Gordon–Taylor model for predicting the plasticising influence of amorphous fenofibrate, leading to less stable CAMs.