Comparative solubility tests at 296 ± 1 K and 310 ± 1 K in 11 solvents, PAMPA permeability measurements at 296 ± 1 K and 310 ± 1 K in water, FaSSIF-V2 and FeSSIF-V2 media, thermoanalytical investigation, and crystallographic characterization were performed on the active pharmaceutical ingredients abiraterone and abiraterone acetate. Both compounds exhibited < 0.5 μg/mL solubility in water. Abiraterone was slightly soluble, while abiraterone acetate was soluble or freely soluble in the organic solvents tested. Both compounds showed increasing solubility in alcohols with longer carbon chain length. Both compounds had the highest solubility in THF, > 10 mg/mL and > 400 mg/mL for abiraterone and abiraterone acetate, respectively, at room temperature. With increasing temperature, the solubility of the compounds only exhibited a marginal increase. Due to their low solubility, abiraterone and its prodrug exhibited very low passive permeability in water and biorelevant media at both 296 ± 1 K and 310 ± 1 K. Abiraterone had a melting point of 501 K. For the acetate ester, a 419 K melting point was measured. Neither abiraterone nor the ester showed weight loss up to 473 K by thermogravimetry, indicating no decomposition. The enthalpy of fusion of abiraterone was approximately twice that of abiraterone acetate. Based on the XRD measurements both compounds were crystalline with intensive Bragg peaks.

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). Four single doses of TOS (from 62.5 to 250 mg) were compared in study C01, and two single doses each of TOS (250 mg) and R-AA (1000 mg) were compared under fasted and fed (modified fasted for R-AA) conditions in C02. Plasma concentrations of abiraterone over time were measured, and pharmacokinetic parameters were calculated. Each doubling of the dose of TOS was associated with a greater than 3-fold increase in exposure. A single dose of TOS (250 mg) exhibited similar exposure over 24 h, whether given fasted (625 ng × h/mL) or fed (485 ng × h/mL). A single dose of TOS (250 mg) was associated with higher (fasted, p = 0.028) or equivalent exposure (fed) compared to 1000 mg R-AA fasted (532 ng × h/mL). Substantially higher exposures were seen with 1000 mg R-AA under modified fasted conditions compared to TOS, irrespective of prandial status (p < 0.001). TOS was generally safe and well tolerated in the study. A 250 mg dose of a novel AA formulation for oral suspension demonstrated bioequivalence to 1000 mg R-AA under fasted conditions. This novel TOS formulation also addresses some of the limitations of current AA treatment, including low bioavailability, high variability in systemic exposure and a large food effect. It may offer an alternative for patients with dysphagia or discomfort with swallowing large pills.