Comparison Between the Pharmacokinetics Data of Ketorolac Tromethamine Wafer a Novel Drug Delivery System and Conventional Ketorolac Tromethamine Tablets to Enhance Patient Compliance Using a New LC-MS/MS Method

摘要

Ketorolac tromethamine (KTM) is a potent and widely used non-steroidal anti-inflammatory drug. Despite its efficacy, it causes gastric irritation and increases the risk of gastrointestinal injuries. This study aimed to formulate KTM wafer to overcome its harmful gastrointestinal side effects. By solvent evaporation method six formulae prepared with different concentrations of polymers of sodium carboxymethyl cellulose, sodium alginate, and hydroxypropyl methylcellulose (HPMC E15). The formula F2 with high concentration of sodium alginate wafer, shows disintegration time in 85 s, with pH 6.6,% drug loaded with 102% and high dissolution release rate in 20 min. Drug release pattern appears to be second order. The mean C(pmax)values of F2 wafer and the marketed product were 2135.47 +/- 13.83 ng/mL and 1073 +/- 23.5, respectively. The median values of T(max)were 1 and 3 h, respectively. The calculated AUC0 - infinity values were 2087 +/- 71.58 and 3981 +/- 62.34 ng h/mL for F2 and marketed product, correspondingly. The relative bioavailability was found to be 0.52. A new rapid, sensitive, and specific LC-MS/MS fully validated method was developed for the determination and quantification of KTM, using torsemide as internal standard, in biological sample. It was successfully applied to perform the pharmacokinetic and the bioavailability study.