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Reducing Burst Release Effect of Freely Water-Soluble Drug Incorporated into Gastro-Floating Formulation Below HPMC Threshold Concentration Through Interpolymer Complex

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Abstract

Undesired-burst release effect is observed in a freely water-soluble drug formulated into a gastro-floating formulation with effervescent (GFFE) delivery system. In order to address this limitation, interpolymer complex (IPC) of two swellable and non-soluble polymers, poly-ammonium methacrylate and poly-vinyl acetate, was incorporated into hydroxypropyl methyl cellulose (HPMC)-based matrix GFFE. This research studied the effect and interaction of the IPC-HPMC blending on the drug release of GFFE using a freely water-soluble drug, metformin HCl, under different threshold concentration levels and curing effect. The interaction between the IPC and HPMC was characterized using vibrational spectroscopy and thermal analyses under curing and swelling conditions. Anti-solvent followed by lyophilization had better physicochemical and physicomechanic properties than spray dying technique. The interaction was observed by a specific shifting of the vibrational peaks and alteration of the thermal behavior pattern. These effects altered the drug release behavior. Thereafter, the IPC reduced burst release effects in the initial time and during testing, and the IPC improved the HPMC matrix robustness under mechanical stress testing below threshold concentration of HPMC matrix formulated in the GFFE.

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Acknowledgments

This research was funded by Indonesian Endowment Fund for Education (LPDP). The authors would like to thank Evonik (Darmstadt, Germany) for providing Eudragit Polymers, BASF (Ludwigshafen, Germany) for providing Kollidon SR, Colorcon (West Point, PA) for providing Methocel K100M DC, and PT Phapros (Semarang, Indonesia) for providing Metformin HCl.

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Authors and Affiliations

  1. Pharmaceutical Technology and Drug Delivery, Pharmaceutics Research Group, Department of Pharmacy, Universitas Sebelas Maret, Ir. Sutami 36A, Surakarta, 57126, Indonesia

    Syaiful Choiri

  2. Department of Pharmaceutics, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia

    T. N. Saifullah Sulaiman

  3. Department of Pharmaceutical Chemistry, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia

    Abdul Rohman

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  1. Syaiful Choiri
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  2. T. N. Saifullah Sulaiman
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  3. Abdul Rohman
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Correspondence to Syaiful Choiri or T. N. Saifullah Sulaiman.

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Choiri, S., Sulaiman, T.N.S. & Rohman, A. Reducing Burst Release Effect of Freely Water-Soluble Drug Incorporated into Gastro-Floating Formulation Below HPMC Threshold Concentration Through Interpolymer Complex. AAPS PharmSciTech 20, 196 (2019). https://doi.org/10.1208/s12249-019-1414-z

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