Benznidazole polymeric particles by an emulsification method: Comparison of spray drying and lyophilization techniques

SEREMETA, KP; BEDOGNI, GR; OKULIK, NB; SALOMON, CJ

Rosario

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

The pharmaceutical industry faces constant challenges concerning the development of different formulations due to biopharmaceutical disadvantages presented by certain drugs, such as the low aqueous solubility shown by up to 40% of available drugs and up to 70% of drugs in the discovery pipeline. Slow dissolution in biological media may lead to erratic absorption and a low and/or variable bioavailability. Particle size reduction of drugs is a convenient approach to increase the dissolution rate of poorly water-soluble molecules. Thus, this work aimed to increase the dissolution efficiency of benznidazole (water solubility 0,4 mg/mL), one of the two drugs approved for Chagas disease, through its encapsulation into polymeric particles. Particles were obtained by simple emulsion (o/w) followed by lyophilization or spray drying. The polymer chosen for achieving the encapsulation was Eudragit® RS PO, which was solubilized with the drug in an organic phase (ethyl acetate or ethanol) and homogenized (16000 rpm, 5 min) with an aqueous phase (distilled water) with Kolliphor® P407 or Sipernat®, according to the posterior drying process (lyophilization or spray drying respectively). Obtained particles were further characterized in size and zeta potential by dynamic light scattering, yielding by weighting and drug loading and encapsulation efficiency by UV-Vis spectrophotometry (λ = 324 nm), and crystallinity by X-ray diffraction. Dissolution efficiency was evaluated by the dialysis membrane method in acid media (HCl 0.1 N) at 37 °C. By lyophilization, nanoparticles were obtained (241 nm ± 4.16), while after spray drying, larger microparticles were obtained (2-3 μm). Both had a positive zeta potential (36.4 mV ± 1.5; 19.47 mV ± 2.95) either for lyophilization or spray drying. The yield of the drying process was 86.8 % ± 4.2 and 47.98 % ± 4.55 after lyophilization and spray drying, respectively. Drug loading and encapsulation efficiency was 18.2 % ± 0.6 and 95.9 % ± 3.5 for lyophilization and 25.23 % ± 0.94 and 94.93 % ± 3.54 for spray drying. A crystallinity reduction of the drug was seen after its encapsulation with both drying processes compared to the untreated drug. The dissolution efficiency of the encapsulated drug was higher than that of the free drug after both drying techniques, increasing up to 1.5 and 2.9 times-fold for lyophilization and up to 1.5 and 3.0 times-fold for spray drying. Therefore, it can be concluded that benznidazole polymeric nano and microparticles were obtained through a simple emulsion (o/w) followed by two different drying techniques with significant increases in dissolution efficiency compared to the free drug, suggesting that spray drying is a reliable alternative for these types of formulations.