Spray-dried benznidazole-loaded microparticles for the treatment of Chagas disease

SEREMETA K.; OKULIC N.; SALOMON C.J

Congreso; IV International Congress in Translational Medicine; 2018

According to recent statistics of the World Health Organization (WHO) about 6 to 7 million people worldwide, mostly in Latin America, are infected with Trypanosoma cruzi, the parasite that causes Chagas disease. In Argentina, nearly 1.5 million people have the disease. Although this disease was discovered more than 100 years ago, even today there are only 2 drugs to treat it and both are in the form of tablets. As a consequence, a pediatric formulation with improved dosing accuracy is urgently needed, due to the cure rate for Chagas disease is almost 100% if treatment occurs early after infection, particularly in pediatric patients. Even though benznidazole (BNZ) is the drug of choice for treating Chagas disease in many countries, its low aqueous solubility limits the further dissolution and absorption in the gastro-intestinal tract resulting in low oral bioavailability. Therefore, administration in large doses and prolonged treatment is required and, as a consequence, a high incidence of adverse reactions and toxicity may occur. One alternative to increase the low aqueous solubility of BNZ is through the microencapsulation process. Spray-drying is a rapid, simple, continuous, easily scalable, cost-effective and reproducible one-step process to obtain microparticles. Thus, the goal of this work was to obtain BNZ-loaded microparticles (BNZ-MPs) using a biocompatible polymer by spray-drying to improve the dissolution profile of drug. The polymer used was Eudragit® RL with well-established mucoadhesive properties due to the presence of cationic groups that would enable the interaction of positively charged particles with negatively charged epithelia that could contribute to improve contact with the intestinal mucosa. BNZ-MPs were obtained by spray-drying (Mini Spray Dryer Büchi B-290) through a two fluid nozzle at inlet air temperature of 130°C. Eudragit® RL and BNZ (2.5:1 ratio) were dissolved in absolute ethanol and added to an aqueous phase before the spray-drying process. The yield (%) of the process was relatively high (~70%). SEM micrographs showed that BNZ-MPs were spherical. Loading capacity (%LC) of BNZ-MPs was high with value of 25% (w/w), approximately. IR spectrum of the BNZ-MPs showed characteristic bands of polymers and BNZ confirming that part of drug remained on the surface of BNZ-MPs. Dissolution studies showed increase in the speed of drug dissolution. The Q20 value of BNZ-MPs was greater (~94%) that non-encapsulated BNZ (~30%). The high dissolution (%) of BNZ could be due to the size reduction of the drug and to that part of BNZ remained on the surface of the BNZ-MPs. Stability studies showed that %LC did not change for up 12 months. In conclusion, the development of spray-dried BNZ-MPs resulted in enhanced drug dissolution compared to the non-encapsulated BNZ and proved to be very stable without reduction of %LC for up one year.