IMPACT OF COMPOSITION AND TECHNOLOGY ON PHARMACOKINETIC PARAMETERS OF FEXOFENADINE HYDROCHLORIDE ORAL SOLUTION: BIOAVAILABILITY STUDY

Fexofenadine hydrochloride (FEX) is one of the leading H₁-receptor antagonists used in the treatment of allergic diseases. However, its low oral bioavailability (~35%) limits its therapeutic efficacy and is primarily attributed to two factors: poor water solubility and active efflux mediated by P-glycoprotein, an efflux transporter. These characteristics highlight the necessity for developing innovative dosage forms with improved biopharmaceutical properties. The objective of this study was to evaluate the impact of mechanochemical treatment (MCT) and compositional formulation on the pharmacokinetic profile of a novel oral solution of fexofenadine hydrochloride. The object of investigation was the "Alfeksa" solution containing 1.2 mg/mL of FEX, 0.4% hydroxypropyl methylcellulose (HPMC), Tween-20, and a buffer system at pH 7.5. The preparation technology involved mechanochemical treatment of the drug substance in a ball mill for 5 minutes, followed by solubilization. Biopharmaceutical studies were conducted in vitro using dialysis in FaSSIF/FeSSIF media and in vivo in rabbits (n = 6, crossover design). The concentration of FEX was analyzed by high-performance liquid chromatography with UV detection (HPLC-UV) using a Synergi Fusion C18 column at a wavelength of 210 nm. Mechanochemical treatment significantly reduced the particle size of FEX from 50.2 ± 3.1 μm to 7.8 ± 0.9 μm (p < 0.01), thereby increasing its solubility by 15.3-fold. In vitro release studies demonstrated prolonged drug release from the new solution: the time to achieve 50% release (T~50%~) was 180 min compared to 45 min for conventional tablets (p < 0.05). In vivo experiments revealed a significant increase in the area under the concentration–time curve (AUC~0–24~) for the new solution—1423.7 ± 156.8 ng·h/mL, which is 159.5% higher than that of the tablet form (892.4 ± 121.3 ng·h/mL; p < 0.01). The combined application of mechanochemical treatment and solubilization, along with the use of HPMC as a matrix, enabled the development of a FEX solution with markedly enhanced bioavailability and a prolonged pharmacokinetic profile. This newly developed formulation shows potential for replacing imported analogs in the pharmaceutical markets of Russia and Iraq, offering improved therapeutic effectiveness and accessibility in the management of allergic conditions.