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

Title
Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique
Author(s)
김종오용철순마라시니니르말트란탄힙포우델비자이조혁준최영근지상철[지상철]최한곤[최한곤]
Keywords
IN-VIVO EVALUATION; MICROENVIRONMENTAL PH; PHYSICOCHEMICAL PROPERTIES; ENHANCED BIOAVAILABILITY; ORAL BIOAVAILABILITY; SOLUBLE DRUGS; SOLUBILITY; PHARMACOKINETICS; DISSOLUTION; MECHANISM
Issue Date
201301
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.441, no.1-2, pp.424 - 432
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 (pH(M)-SDs) exhibited marked improvement in the dissolution behavior when compared with crystalline TMS powder. The optimum formulation of pH(M)-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 pH(M)-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. (C) 2012 Elsevier B. V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/26792http://dx.doi.org/10.1016/j.ijpharm.2012.11.012
ISSN
0378-5173
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약학대학 > 약학부 > Articles
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