Dose Finding and Food Effect Studies of a Novel Abiraterone Acetate Formulation for Oral Suspension in Comparison to a Reference Formulation in Healthy Male Subjects.

Currently approved formulations of the androgen synthesis inhibitor abiraterone acetate (AA) consist of multiple tablets administered daily in a fasted state. Removing the food effect and switching to a suspension formulation is expected to improve the pharmacokinetic profile and facilitate drug administration for patients with late-stage prostate cancer. Two four-sequence, four-period randomized crossover investigations were undertaken to establish the pharmacokinetic profiles of single doses of commercially available Zytiga, as the reference AA (R-AA), and a novel tablet for oral suspension (TOS).

Dose Escalation Study to Assess the Pharmacokinetic Parameters of a Nano-amorphous Oral Sirolimus Formulation in Healthy Volunteers.

Background And Objectives: Sirolimus (Rapamune) exhibits low bioavailability, high variability and moderate food effect following oral administration. This makes therapeutic blood monitoring of sirolimus concentrations necessary for kidney transplant patients. Furthermore, reaching therapeutic blood sirolimus concentrations in renal cancer patients was found to be challenging when the marketed drug was administered alone.

Preparation, Pre-clinical and Clinical Evaluation of a Novel Rapidly Absorbed Celecoxib Formulation.

Celecoxib (Celebrex®) is the only widely used NSAID that selectively inhibits the COX-2 isoenzyme. Celebrex® is absorbed slowly in the fasted state and food intake further delays absorption. In this work, an amorphous water dispersible granule formulation of celecoxib is described with in vitro characterization, preclinical and clinical data.

Investigations of the mechanism behind the rapid absorption of nano-amorphous abiraterone acetate.

Abiraterone acetate is indicated for patients with metastatic castration resistant prostate cancer. The marketed drug product (Zytiga®) exhibits very low bioavailability in the fasted state and a substantial positive food effect. We recently developed a nano-amorphous formulation of this drug which exhibited higher apparent solubility and dissolution rate, and significantly improved absorption and bioavailability in the fasted state in beagle dogs and in a phase I clinical study.

Development of an abiraterone acetate formulation with improved oral bioavailability guided by absorption modeling based on in vitro dissolution and permeability measurements.

Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability.

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

Purpose: Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics.