title: Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.
abstract: The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y1), percentage friability (Y2), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher Cmaxand (AUC0-12) and shorter Tmaxthan those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: El-Shenawy
authors.affiliation: Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Ahmed
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Minia University, P.O.Box 61111, Minia, Egypt. drhf2000@hotmail.com.
authors.forename: Heba F
authors.initials: HF
authors.lastname: Mansour
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors.forename: Saleh
authors.initials: S
authors.lastname: Abd El Rasoul
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics; D010592:Pharmaceutic Aids / Q000737:chemistry / Q000493:pharmacokinetics; D011205:Povidone / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics; D013549:Sweetening Agents / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets; D000077786:Torsemide
chemical_list: D000959:Antihypertensive Agents; D005079:Excipients; D010592:Pharmaceutic Aids; D013449:Sulfonamides; D013549:Sweetening Agents; D013607:Tablets; D013012:Sorbitol; D011205:Povidone; D002266:Carboxymethylcellulose Sodium; D000077786:Torsemide
keywords: Box–Bhenken design; fast dissolving tablets; pharmacokinetic parameters; solid dispersion; sorbitol; torsemide