Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique

Marasini, Nirmal, Tran, Tuan Hiep, Poudel, Bijay Kumar, Cho, Hyuk Jun, Choi, Young Keun, Chi, Sang-Cheol, Choi, Han-Gon, Yong, Chul Soon and Kim, Jong Oh (2013) Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique. International Journal of Pharmaceutics, 441 1-2: 424-432. doi:10.1016/j.ijpharm.2012.11.012

Author Marasini, Nirmal
Tran, Tuan Hiep
Poudel, Bijay Kumar
Cho, Hyuk Jun
Choi, Young Keun
Chi, Sang-Cheol
Choi, Han-Gon
Yong, Chul Soon
Kim, Jong Oh
Title Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
Publication date 2013-01-30
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2012.11.012
Open Access Status Not Open Access
Volume 441
Issue 1-2
Start page 424
End page 432
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Formatted abstract
The present study was undertaken to overcome the problems associated with solubility, dissolution and oral bioavailability of a poorly water-soluble ionizable drug, telmisartan (TMS). For these purposes, a solubility test was carried to select the appropriate formulation composition from various carriers and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to-carrier ratios by the spray-drying technique, and were characterized by dissolution and aqueous solubility studies. The optimum formulation was investigated by dissolution studies at different pH and water media and its solid state characterisations were performed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In solubility and dissolution tests, all TMS-loaded pH-modulated SDs (pHM-SDs) exhibited marked improvement in the dissolution behavior when compared with crystalline TMS powder. The optimum formulation of pHM-SD consisted of TMS/PVP (polyvinylpyrrolidone) K30/Na2CO3 at a weight ratio of 2/0.5/3 and showed significant improvement in the aqueous solubility and dissolution rate by approximately 40,000- and 3-fold, respectively, compared to TMS powder. Solid-state characterization revealed the changed in crystallinity of TMS into amorphous state. Furthermore, area under the drug concentration time-curve (AUC) of TMS from the pHM-SD increased by 13.4- and 2.1-fold, compared with TMS powder and commercial product, respectively. According to these observations, taken together with dissolution and pharmacokinetic behaviors, pH-modulated SD in the presence of an alkalizer for a poorly water-soluble ionizable drug, TMS, appeared to be efficacious for enhancing its bioavailability.
Keyword Alkalizer
Solid dispersion
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2010-0024185
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 04 Jun 2016, 21:55:10 EST by Nirmal Marasini on behalf of Learning and Research Services (UQ Library)