Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance.

The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. Supersaturated amorphous drug-salt-polymer systems provide an emergent approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug.

Amorphous Salts Solid Dispersions of Celecoxib: Enhanced Biopharmaceutical Performance and Physical Stability.

Numerous amorphous solid dispersion (ASD) formulations of celecoxib (CEL) have been attempted for enhancing the solubility, dissolution rate, and in vivo pharmacokinetics via high drug loading, polymer combination, or by surfactant addition. However, physical stability for long-term shelf life and desired in vivo pharmacokinetics remains elusive. Therefore, newer formulation strategies are always warranted to address poor aqueous solubility and oral bioavailability with extended shelf life.

Identification and characterization of novel metabolites of nintedanib by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry with in silico toxicological assessment.

Rationale: Nintedanib, an oral, triple angiokinase inhibitor, is used alongside docetaxel in the management of locally recurrent non-small-cell lung cancer and idiopathic pulmonary fibrosis. The present study deals with the identification and characterization of in vitro and in vivo stable and reactive (if any) metabolites of nintedanib and sheds light on some novel metabolites of the drug which have not been reported previously.

Methods: The study involved an oral administration of the drug to male Wistar rats, followed by collection of the biological matrices (urine, plasma and feces) at specific intervals for determination of in vivo metabolites.

In vivo metabolic investigation of cetilistat in normal versus pseudo-germ-free rats using UPLC-QTOFMS/MS and in silico toxicological evaluation of its metabolites.

Cetilistat (CET) is a pancreatic lipase inhibitor approved for management of obesity after the serious adverse effects exhibited by its analogue orlistat. Exhaustive literature review reveals lack of comprehensive reports on its biotransformation. With a view to study the same, the present study reports the identification and characterization of metabolites of CET in rats using UPLC-MS/MS.

In vitroand in vivo investigation of metabolic fate of riociguat by HPLC-Q-TOF/MS/MS and in silico evaluation of the metabolites by ADMET predictor.

Riociguat, a guanyl cyclase inhibitor, is one of its kind drug regimen approved for management of pulmonary arterial hypertension and chronic thromboembolism pulmonary hypertension. Extensive literature review indicates lack of comprehensive reports on its metabolic fate. The present study reports the in vivo and in vitro identification and characterization of metabolites of riociguat, using high-performance liquid chromatography-quadruple time-of-flight tandem mass spectrometry.

Enhanced Biopharmaceutical Performance of Rivaroxaban through Polymeric Amorphous Solid Dispersion.

Rivaroxaban (RXB) is an orally active direct inhibitor of the activated serine protease Factor Xa, given as monotherapy in the treatment of venous thromboembolism (VTE). It has been characterized in vitro as a substrate for the active, nonsaturable efflux via P-gp transporter, limiting its high permeability. Therefore, the role of P-gp inhibiting polymers in enhancing the biopharmaceutical performance of RXB by preparing polymeric amorphous solid dispersion and subsequent improvement in solubility and permeability was investigated.