title: Development, evaluation and pharmacokinetics of time-dependent ketorolac tromethamine tablets.
abstract: OBJECTIVE
  The present study was intended to develop a time-dependent colon-targeted compression-coated tablets of ketorolac tromethamine (KTM) using hydroxypropyl methylcellulose (HPMC) that release the drug slowly but completely in the colonic region by retarding the drug releases in stomach and small intestine.
  
  
  METHODS
  KTM core tablets were prepared by direct compression method and were compression coated with HPMC. The formulation is optimized based on the in vitro drug release studies and further evaluated by X-ray imaging technique in healthy humans to ensure the colonic delivery. To prove these results, in vivo pharmacokinetic studies in human volunteers were designed to study the in vitro-in vivo correlation.
  
  
  CONCLUSIONS
  From the in vitro dissolution study, optimized formulation F3 showed negligible drug release (6.75 ± 0.49%) in the initial lag period followed by slow release (97.47 ± 0.93%) for 24 h which clearly indicates that the drug is delivered to the colon. The X-ray imaging studies showed that the tablets reached the colon without disintegrating in upper gastrointestinal system. From the pharmacokinetic evaluation, the immediate-release tablets producing peak plasma concentration (C(max)) was 4482.74 ng/ml at 2 h T(max) and colon-targeted tablets showed C(max) = 3562.67 ng/ml at 10 h T(max). The area under the curve for the immediate-release and compression-coated tablets was 10595.14 and 18796.70 ng h/ml and the mean resident time was 3.82 and 10.75 h, respectively.
  
  
  CONCLUSIONS
  Thus, the compression-coated tablets based on time-dependent approach were preferred for colon-targeted delivery of ketorolac.
authors.affiliation: Chaitanya College of Pharmacy Education and Research, Department of Pharmaceutics, Kishanpura, Hanamkonda, Warangal, Andhra Pradesh, 506001, India.
authors.forename: Sateesh Kumar
authors.initials: SK
authors.lastname: Vemula
authors.forename: Prabhakar Reddy
authors.initials: PR
authors.lastname: Veerareddy
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000000981:diagnostic imaging / Q000378:metabolism*; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D065347:Hypromellose Derivatives; D020911:Ketorolac Tromethamine / Q000737:chemistry / Q000493:pharmacokinetics*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations; D011859:Radiography; D017550:Spectroscopy, Fourier Transform Infrared; D013608:Tablets, Enteric-Coated / Q000737:chemistry; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D013608:Tablets, Enteric-Coated; D065347:Hypromellose Derivatives; D020911:Ketorolac Tromethamine; D008747:Methylcellulose