Torsemide Fast Dissolving Tablets: Development, Optimization Using Box–Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment

Autor: Heba F. Mansour, Mahmoud M. Ahmed, Ahmed A El-Shenawy, Saleh Abd El Rasoul
Rok vydání: 2017
Předmět:
Materials science
Drug Compounding
Biological Availability
Pharmaceutical Science
Excipient
02 engineering and technology
Aquatic Science
Friability
030226 pharmacology & pharmacy
Excipients
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Spectroscopy
Fourier Transform Infrared
Drug Discovery
Pharmaceutic Aids
medicine
Animals
Sorbitol
Response surface methodology
Antihypertensive Agents
Ecology
Evolution
Behavior and Systematics
Croscarmellose sodium
Sulfonamides
Chromatography
Calorimetry
Differential Scanning
Ecology
Polyvinylpyrrolidone
Povidone
Torsemide
General Medicine
Factorial experiment
021001 nanoscience & nanotechnology
Bioavailability
Solubility
chemistry
Carboxymethylcellulose Sodium
Sweetening Agents
Rabbits
0210 nano-technology
Agronomy and Crop Science
Tablets
medicine.drug
Zdroj: AAPS PharmSciTech. 18:2168-2179
ISSN: 1530-9932
DOI: 10.1208/s12249-016-0697-6
Popis: 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 C max and (AUC0-12) and shorter T max than 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.
Databáze: OpenAIRE
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