Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan.

Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan.

Chae, Jun Soo;Chae, Bo Ram;Shin, Dong Jun;Goo, Yoon Tae;Lee, Eun Seok;Yoon, Ho Yub;Kim, Chang Hyun;Choi, Young Wook;
aaps pharmscitech 2018 Vol. 19 pp. 2990-2999
264
chae2018tabletaaps

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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44783
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10.1208/s12249-018-1124-y
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