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Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan

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Abstract

To overcome the poor dissolution of telmisartan (TMS) at weak acidic pH, amorphous alkalinized TMS (AAT) was prepared by introducing sodium hydroxide as a selective alkalizer. AAT-containing polymeric solid dispersions were prepared by a solvent evaporation method; these solid dispersions were AAT-PEG, AAT-PVP, AAT-POL, and AAT-SOL for the polymers of PEG 6000, PVP K30, Poloxamer 407, and Soluplus, respectively. The characteristics of the different formulations were observed by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. To compare the supersaturation behavior, a dissolution test was performed at 37 ± 0.5 °C either in 900 ml (plain condition) or 500 ml (limited condition) of pH 6.8-simulated intestinal fluid used as a medium. AAT-SOL exhibited enhanced dissolution, indicating the probability of extended supersaturation in the limited condition. AAT-SOL was further formulated into a tablet by introducing other excipients, Vivapur 105 and Croscarmellose, as a binder and superdisintegrant, respectively, using a direct compression method. The selected AAT-SOL tablet was superior to Micardis (the reference product) in the aspect of supersaturation maintenance during dissolution in the limited condition, suggesting that it is a promising candidate for practical development that can replace the commercial product in the future.

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Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2016R1A2B4011449). This work also supported in part by the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (HI17C0710), and the Advanced Technology Center program (10051950) funded by the Ministry of Trade, Industry and Energy (MI, Korea).

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Author notes

  1. Jun Soo Chae and Bo Ram Chae contributed equally to this work

Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul, 06974, Republic of Korea

    Jun Soo Chae, Bo Ram Chae, Dong Jun Shin, Yoon Tae Goo, Eun Seok Lee, Ho Yub Yoon, Chang Hyun Kim & Young Wook Choi

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  1. Jun Soo Chae
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  2. Bo Ram Chae
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  3. Dong Jun Shin
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  8. Young Wook Choi
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Correspondence to Young Wook Choi.

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Chae, J.S., Chae, B.R., Shin, D.J. et al. Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan. AAPS PharmSciTech 19, 2990–2999 (2018). https://doi.org/10.1208/s12249-018-1124-y

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  • DOI: https://doi.org/10.1208/s12249-018-1124-y

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