title: Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique.
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/Na(2)CO(3) 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.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyungsan, Gyungbuk 712-749, South Korea.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Marasini
authors.forename: Tuan Hiep
authors.initials: TH
authors.lastname: Tran
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Poudel
authors.forename: Hyuk Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Choi
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Chi
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001565:Benzoates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002254:Carbonates / Q000737:chemistry; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008855:Microscopy, Electron, Scanning; D011205:Povidone / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000077333:Telmisartan; D014961:X-Ray Diffraction
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D002254:Carbonates; D004337:Drug Carriers; D005079:Excipients; C005686:sodium carbonate; D011205:Povidone; D000077333:Telmisartan