Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor.

Apremilast is a selective PDE4 inhibitor and has been approved for several inflammatory disorders. It is classified as a BCS-IV drug and has 7 polymorphic forms. In this research we report the development of an ASD based sustained-release (SR) drug delivery system. A simplified material sparing ASD formulation approach was employed to identify ideal carrier polymers for optimum drug loadings. HPMCAS-M at 20% and Copovidone at 40% drug loadings were selected as the lead formulations. A stable single-phase amorphous system of apremilast via spray drying was created and fully characterized by mDSC, XRPD, DMA, micro-dissolution, dissolution, and accelerated stability analysis. Micro-dissolution study of ASD confirmed attainment and maintenance of supersaturated state over 3 h. ASD showed 8-fold higher solubility relative to its crystalline counterpart. Novel monolithic and bilayer SR HPMC tablet matrices containing 30 mg or 60 mg of ASD system were manufactured. Tablets during dissolution exhibited gradual swelling, erosion, and disentanglement over 15-20-hours with over 90% drug released. The designed SR amorphous based matrix system showed ability to increase apremilast solubility, dissolution rate, and inhibit recrystallization or polymorphic interconversion by stabilizing its amorphous form. This new development may allow for once-daily drug administration and improve both bioavailability and patient compliance. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Qiangnan Zhang, Thomas Durig, Benjamin Blass, Reza Fassihi. Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor. International journal of pharmaceutics. 2022 Mar 05;615:121516

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PMID: 35091003

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