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Purpose <p>The study aimed to formulate a novel once-a-day Controlled Release Tablets of Apremilast Solid Dispersion (CRTASD) and design a discriminatory dissolution condition for the release behaviour of the said CRTASD.</p> Methods <p>Apremilast was formulated into an amorphous solid dispersion with Kollidon® VA 64 (1:2) by QbD-enabled hot melt extrusion (HME) on the basis of solubility studies. The extrudates were mixed with high-viscosity Hypromellose (Methocel K100 LVCR) as a controlled release agent, colloidal silicon dioxide as glidant, and stearic acid as lubricant to form tablets. Initial dissolution parameters were determined using the One Factor at A Time (OFAT) method, later refined through the Design of Experiment (DoE) with three variables—agitation speed, media volume, and surfactant concentration that validate the dissolution method, resulting in a curated design space based on the defined specifications. The discriminatory capacity of the finalized dissolution media was evaluated by altering critical quality attributes (CQAs) like controlled release polymer level and critical process parameters (CPP) like tablet hardness.</p> Results <p>Dissolution parameters such as pH (4.5), surfactant concentration (1%w/w Tween® 80), volume (900&#xa0;mL), agitation speed (75&#xa0;rpm), and apparatus (type II) were found to significantly influence discriminatory ability of selected dissolution condition, enabling the detection of minor variations in formulation attributes and manufacturing process parameters.</p> Conclusion <p>This QbD-DoE based study of formulation development and design&#xa0;of discriminatory dissolution of offers a novel once a day Controlled Release Tablets of Apremilast Amorphous Solid Dispersion (CRASD) substitute to the traditional high dose multi-frequency regime of immediate release tablets. Effective discriminatory dissolution condition ensures reliable product performance and able to detect minor formulation or process changes.</p> Graphical Abstract <p></p>

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Formulation Design and Discriminatory Dissolution Method Development of Controlled-release Tablets of Apremilast Solid Dispersion for Once a Day Administration: a QbD Approach

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Sandipan Roy,
  • Apoorva Phadke,
  • Nehal Sarvaiya,
  • Vaishali Londhe,
  • Sujata Sawarkar

摘要

Purpose

The study aimed to formulate a novel once-a-day Controlled Release Tablets of Apremilast Solid Dispersion (CRTASD) and design a discriminatory dissolution condition for the release behaviour of the said CRTASD.

Methods

Apremilast was formulated into an amorphous solid dispersion with Kollidon® VA 64 (1:2) by QbD-enabled hot melt extrusion (HME) on the basis of solubility studies. The extrudates were mixed with high-viscosity Hypromellose (Methocel K100 LVCR) as a controlled release agent, colloidal silicon dioxide as glidant, and stearic acid as lubricant to form tablets. Initial dissolution parameters were determined using the One Factor at A Time (OFAT) method, later refined through the Design of Experiment (DoE) with three variables—agitation speed, media volume, and surfactant concentration that validate the dissolution method, resulting in a curated design space based on the defined specifications. The discriminatory capacity of the finalized dissolution media was evaluated by altering critical quality attributes (CQAs) like controlled release polymer level and critical process parameters (CPP) like tablet hardness.

Results

Dissolution parameters such as pH (4.5), surfactant concentration (1%w/w Tween® 80), volume (900 mL), agitation speed (75 rpm), and apparatus (type II) were found to significantly influence discriminatory ability of selected dissolution condition, enabling the detection of minor variations in formulation attributes and manufacturing process parameters.

Conclusion

This QbD-DoE based study of formulation development and design of discriminatory dissolution of offers a novel once a day Controlled Release Tablets of Apremilast Amorphous Solid Dispersion (CRASD) substitute to the traditional high dose multi-frequency regime of immediate release tablets. Effective discriminatory dissolution condition ensures reliable product performance and able to detect minor formulation or process changes.

Graphical Abstract