Pharmacokinetic evaluation in dogs of a prolonged release lipid ink containing ricobendazole obtained through a printing process based on fusion solidification (MESO-PP).

BARBERIS, MARÍA EUGENIA; MARÍA DEL PILAR ZARAZAGA ; NICOLÁS. J, LITTERIO ; PALMA, SANTIAGO DANIEL ; SERGIO SANCHEZ BRUNI; CANTÓN, LUCILA ; REAL, JUAN PABLO

Rosario- Santa Fe

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2023); 2023

Universidad Nacional de Rosario

Ricobendazole (RBZ), a benzimidazole used in the treatment of helminthiasis, has low solubility in aqueous medium, which leads to poor gastrointestinal dissolution, limited absorption and a deficiency in its therapeutic efficacy. The printing process based on melting by solidification (MESO-PP) allows obtaining gastro-retentive systems using RBZ accompanied by a Gelucire 50/13 carrier polymer in order to improve their bioavailability. The objective of this work was to design through RBZ gastro-retentive solid printed (IS) MESO-PP to compare the in vitro biopharmaceutical behavior with the pharmacokinetic performance and therapeutic response in dogs. 25% RBZ and 75% Gelucire 50/13 were used to formulate the solid dispersion (DS) by melt. The DS loaded into 1 ml syringes was combined with the MESO-PP printing process that allowed RBZ-IS to be obtained. DS and RBZ placed in hard gelatin capsules were used as controls. In the pharmacokinetic study, RBZ-C, DS-C and RBZ-IS were administered orally at a dose of 25 mg/kg to 6 healthy dogs (between 2 and 5 years, mean weight 12.75 ± 3.60 kg) that were randomly selected. in 3 groups of 2 and received the 3 treatments. The dogs were fasted for 12 hours before and after the treatment received. The study design was crossover in which 3 phases were carried out with washout periods of 15 days. Blood samples were taken at the initial time and at certain times after starting treatment for subsequent analysis. The plasma was centrifuged and the sample was extracted using C18 cartridges. These were evaporated and reconstituted. RBZ concentrations in plasma were analyzed and quantified by high-performance liquid chromatography (HPLC). In vitro release studies demonstrated that RBZ-IS in acidic medium (2h:59.09±4.27%; 3h:78.10±6.38%) resulted in improved behavior with respect to DS-C (46.78±3.92%; 3h: 59.31±2.87%) used as control. However, in simulated intestinal fluid the RBZ-IS (2h:62.33±7.49%; 3h:65.84±2.16%) were even better since it represents what happens in vivo with respect to DS-C used as a control (46.79± 3.92%; 3h:48.55±3.52%). While the results of the pharmacokinetic study demonstrated that RBZ-IS exhibit a higher pharmacokinetic behavior with respect to control and DS-C, with a significant increase in Cmax (24.78 μg/ml for RBZ-IS, 13.14 μg/ml DS-C and 4.19 μg/ml RBZ) and AUC∞ values (249.97 μg·h/ml for RBZ-IS, 130.70 μg·h/ml DS-C and 35.80 μg·h/ml RBZ) showing statistically differences significant between treatments in terms of Cmax and AUC∞. Tmáz did not show differences between treatments. Consequently, the pharmacokinetic study of RBZ-IS demonstrated a significant increase in the oral absorption of the drug, with an AUC∞ 7 times greater than that obtained in dogs treated with RBZ, and an AUC∞ 1.9 times greater than that obtained in dogs treated with DS-C. This new MESO-PP methodology allowed obtaining prolonged release RBZ gastro-retentive systems with an improved pharmacokinetic profile using an innovative, single-step and potentially scalable process.