Prediction of in-vivo pharmacokinetic profile for immediate and modified release oral dosage forms of furosemide using an in-vitro-in-silico-in-vivo approach.

摘要: Objectives To develop a physiologically based pharmacokinetic (PBPK) model for furosemide immediate release (IR) tablets and modified (MR) capsules by coupling biorelevant dissolution testing results with (PK) physiologic parameters, to investigate the key factors influencing absorption using simulation approaches PBPK model. Methods Using solubility, kinetics, gastrointestinal (GI) parameters disposition was developed STELLA software. Solubility profiles both formulations were evaluated in compendial media. The simulated plasma compared in-vivo point estimates of area under concentration-time curve, maximal concentration after dose time dose. Key findings Simulated IR MR similar observed profile terms PK parameters. Sensitivity analysis tablet indicated that gastric emptying rate have an influence on profile. For capsules, sensitivity suggested small intestine, all profile. Conclusions A predictive describe dosage forms containing attained. Because is able identify profile, this in-vitro–in-silico–in-vivo approach could be useful tool facilitating formulation development drug products.