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<p>To deliver Mesalamine (MSA) in the treatment of Ulcerative Colitis (UC) at the targeted site of action, numerous modified release formulations have been developed to release the drug in colon that are coated with pH dependent delayed release (DR) polymer. Such pH dependent formulations have a significant degree of unpredictability in terms of their drug release as the intraluminal pH varies with population. Also, postprandial administration of such formulations pose unpredictable drug release patterns when compared to the fasted state. Available <i>in vitro</i> methods overlook physiological aspects impacting drug release and lack the ability to predict the <i>in vivo</i> performance of a test formulation. Here, we have developed a discriminatory/ bio-predictive dissolution (DBD)&#xa0;method for a DR formulation of MSA that considers postprandial GI pH gradient, ionic strength and surfactant concentration to discriminate test formulations based on their <i>in vivo</i> behaviour. The required pH gradient, time of treatment, use of osmotic agent and bio-relevant surfactants was optimized based on comparative <i>in vivo</i> observations of reference and test formulations. A linear relationship between formulation variable (amount of release controlling polymer) and <i>in vitro</i> drug release in the developed dissolution condition was observed (regression coefficient &gt; 0.99). Further, a Level A <i>in vitro</i> <i>in vivo</i> correlation (IVIVIC) was developed using <i>in vivo</i> pharmacokinetic data (PK) from a bioequivalence (BE) study and <i>in vitro</i> drug release from the developed dissolution method to predict the behavior of test formulations with average prediction error less than 10%.</p> Graphical Abstract <p></p>

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Development of a pH Gradient Dissolution Condition to Predict the Behavior of Delayed Release Formulations under Fed In Vivo Condition

  • 期刊论文

  • 发表日期：

    2025年8月11日

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  • Juilee Kulkarni,
  • Usha Nayak,
  • Bibhuranjan Panigrahi,
  • Sajeev Chandran

摘要

To deliver Mesalamine (MSA) in the treatment of Ulcerative Colitis (UC) at the targeted site of action, numerous modified release formulations have been developed to release the drug in colon that are coated with pH dependent delayed release (DR) polymer. Such pH dependent formulations have a significant degree of unpredictability in terms of their drug release as the intraluminal pH varies with population. Also, postprandial administration of such formulations pose unpredictable drug release patterns when compared to the fasted state. Available in vitro methods overlook physiological aspects impacting drug release and lack the ability to predict the in vivo performance of a test formulation. Here, we have developed a discriminatory/ bio-predictive dissolution (DBD) method for a DR formulation of MSA that considers postprandial GI pH gradient, ionic strength and surfactant concentration to discriminate test formulations based on their in vivo behaviour. The required pH gradient, time of treatment, use of osmotic agent and bio-relevant surfactants was optimized based on comparative in vivo observations of reference and test formulations. A linear relationship between formulation variable (amount of release controlling polymer) and in vitro drug release in the developed dissolution condition was observed (regression coefficient > 0.99). Further, a Level A in vitro in vivo correlation (IVIVIC) was developed using in vivo pharmacokinetic data (PK) from a bioequivalence (BE) study and in vitro drug release from the developed dissolution method to predict the behavior of test formulations with average prediction error less than 10%.

Graphical Abstract