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Design and Mechanism of On–Off Pulsed Drug Release Using Nonenteric Polymeric Systems via pH Modulation

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  • Theme: Advanced Technologies for Oral Controlled Release
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Abstract

The aim was to design a pH-sensitive pulsatile drug delivery system that allows for an on–off pulsed release of a drug using polyacrylic acid (PAA) blended with ethyl cellulose (EC) in different ratios. PAA, a polyelectrolyte polymer, exhibits a highly coiled conformation at low pH but a highly extended structure at high pH. Fumaric acid, which is an internal acidifying agent, was incorporated into the hydroxypropyl methylcellulose-based core tablets to create an acidic microenvironmental pH (pHM). The concentration of fumaric acid inside the core tablet and the ratio of PAA/EC in the coating layer were very crucial in modulating drug release behaviors. When the fumaric acid was retained in the core tablet, it gave a more acidic pHM, so that the PAA was kept in a highly coiled state in the coated film, which hindered drug release (“off” release pattern). Interestingly, the release profiles of the drug and fumaric acid from coated tablets showed the on–off pulsed pattern upon dissolution. Imaging analyses using scanning electron microscopy, near-infrared imaging, confocal laser scanning microscopy, and Fourier transform infrared spectroscopy confirmed this on–off release behavior of the drug and fumaric acid from coated tablets.

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ACKNOWLEDGMENTS

This work was supported by the 2009 Small Business Administration, BK21 program and a grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. We would like to thank the Central Research Laboratory (Kangwon National University) for the use of the FTIR and SEM and the Research Institute of Pharmaceutical Sciences, Kangwon National University, for the use of their HPLC systems. Finally, we acknowledge KBSI (Chuncheon, Korea) for the CLSM and KAIST (Daejeon, Korea) for the NIR imaging.

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Authors and Affiliations

  1. Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon, 200-701, South Korea

    Phuong Ha-Lien Tran, Thao Truong-Dinh Tran, Young Min Park & Beom-Jin Lee

  2. EuraPharm Inc, Suwon, South Korea

    Jae-Seung Choe

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  1. Phuong Ha-Lien Tran
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  2. Jae-Seung Choe
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Correspondence to Beom-Jin Lee.

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Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

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Tran, P.HL., Choe, JS., Tran, T.TD. et al. Design and Mechanism of On–Off Pulsed Drug Release Using Nonenteric Polymeric Systems via pH Modulation. AAPS PharmSciTech 12, 46–55 (2011). https://doi.org/10.1208/s12249-010-9562-1

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