Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor indicated in adults for the treatment of major depressive disorder, diabetic peripheral neuropathic pain, and generalized anxiety disorder. The aim of these studies was to evaluate the effect of food on the pharmacokinetics and safety of duloxetine 60-mg gastroresistant hard capsules following single-dose administration. The data were obtained from 2 phase 1 bioequivalence studies, 1 in a fasting state and the other under fed conditions. Both studies have shown that, when administered as a single dose in the same prandial state, the test and reference duloxetine treatments were bioequivalent and exhibited similar safety profiles. The mean fed and fasting pharmacokinetic parameters and drug-related adverse events from the 2 studies were compared in order to assess the effect of food on the duloxetine bioavailability and respectively, tolerability. Administration of duloxetine in fed conditions increased peak plasma concentration by up to 30% and delayed mean time to peak concentration by an average of 1.15 hours while having an insignificant effect on extent of absorption (area under the plasma concentration-time curve in fed state within ±6% as compared with fasting conditions). Even though peak plasma levels were substantially higher in the fed state, there was no negative impact on the drug's safety profile. Actually, administration with food resulted in a lower average number of adverse events per single dose exposure. The negligible variation in overall systemic exposure suggests that efficacy remains unchanged irrespective of administration conditions; however, a better tolerability of the 60-mg dose is expected when the drug is taken with food.

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The bioavailability of an active substance might be altered when a solid oral dosage form (SODF) is crushed or disintegrated and mixed with fluids or food in order to assist swallowing. In consequence, the current European Medicines Agency (EMA) practice is to request comparative bioavailability testing for bridging safety and efficacy data from a formulation administered whole to the same product administered crushed. Specific criteria for waiving in vivo testing of crushed products are available only for BCS Class I and Class III drugs. Since rivaroxaban is a Class II drug which can be administered crushed and mixed with fluids, any generic formulation has to be tested against the originator in this setting. Therefore, an open label, randomized, single dose, two-period, two-sequence, crossover bioequivalence study with administration of rivaroxaban 10 mg crushed tablets suspended in apple puree was conducted in 24 fasting healthy volunteers. Both rivaroxaban treatments were well tolerated by the study subjects. A standardized, dose efficient and fully reproducible protocol for grinding, mixing and administering investigational medicinal products was developed and applied. Assessment of bioequivalence was based on plasma concentrations of parent rivaroxaban, quantified using a validated HPLC/MS/MS method. The 90% confidence intervals for C max and AUC 0-t least square mean T/R ratios were within the bioequivalence acceptance range of 80% to 125%. Results from the present study reinforced the bioequivalence conclusion reached for the same test and reference products following administration of whole tablets in fasting state. No notable changes in bioavailability occurred when rivaroxaban tablets were crushed, immediately dispensed in 70 mL apple puree and quantitatively (entire dose recovered) administered to fasting volunteers.

A generic formula containing 14 mg of teriflunomide (Terflimida ® test formulation) in oral coated tablets was compared to the reference product (Aubagio ®) in a pharmacokinetic, open label, two-periods, two sequences, two-way crossover; block randomized single dose study in healthy male volunteers under fasting conditions.The statistical analysis of the pharmacokinetic data obtained in this study showed that the Teriflunomide formulations: Terflimida ® coated tablets 14 (test formulation) and Aubagio ® 14 mg coated tablets (reference formulation), were bioequivalent regarding the rate (C max) and the extent of absorption (AUC0-72), under fasting conditions. The Teriflunomide treatments (TEST and REFERENCE formulations), administered orally in single dose, to male healthy volunteers, under fasting conditions, were very well tolerated by all the participating subjects.

The rate and extent of absorption of drugs belonging to Biopharmaceutics Classification System class II are rate‐limited by dissolution and highly dependent on the performance of the formulated product. The purpose of the present study was to investigate the potential impact of a surfactant and the particle size of the active substance on the in vitro drug dissolution profiles and in vivo pharmacokinetics of the poorly soluble drug posaconazole. A comparative physicochemical evaluation was conducted, and 3 formulations of posaconazole oral suspension were tested in various dissolution media compared with the reference product. In addition, a comparative bioavailability study was conducted in healthy volunteers under high‐fat fed conditions. Bioequivalence was assessed based on plasma concentrations of the parent drug (posaconazole) measured by a validated high‐pressure liquid chromatography‐tandem mass spectrometry method. The 90% confidence intervals for Cmax and AUC0‐72 least‐squares mean T/R ratios of all 3 posaconazole formulations were within the bioequivalence acceptance range of 80.00% to 125.00%. The study was useful in the formulation development process and demonstrated that neither surfactant type nor particle size of the active substance within the studied range affected the extent or rate of absorption of posaconazole under the tested fed conditions.