Background/Objectives: Fungal infections caused by Candida species remain a significant clinical challenge, exacerbated by limitations in current antifungal therapies, including toxicity and poor bioavailability. This study aimed to develop and evaluate voriconazole-loaded zein–pectin–hyaluronic acid nanoparticles (ZPHA-VRC NPs) as a novel drug delivery system to enhance efficacy and reduce toxicity. Alternative in vitro and in vivo models were utilized to assess the safety and therapeutic potential of the nanoparticles. Methods: ZPHA-VRC NPs were prepared using a nanoprecipitation method and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Antifungal activity was assessed via MIC assays against Candida albicans, C. krusei, and C. parapsilosis. Cytotoxicity was evaluated on Vero cells, while in vivo toxicity and efficacy were assessed using Galleria mellonella and Caenorhabditis elegans models. The therapeutic efficacy was further evaluated in an infected Caenorhabditis elegans model using survival and health scores. Results: ZPHA-VRC nanoparticles exhibited favorable physicochemical properties, including a particle size of approximately 192 nm, a polydispersity index of 0.079, a zeta potential of −24 mV, and an encapsulation efficiency of 34%. The nanoparticles retained antifungal activity comparable to free voriconazole while significantly reducing cytotoxicity. In vivo studies using G. mellonella and C. elegans demonstrated that ZPHA-VRC NPs markedly improved survival rates, reduced fungal burden, and enhanced health scores in infected models, outperforming the free drug. Additionally, the nanoparticles exhibited a superior safety profile, minimizing systemic toxicity while maintaining therapeutic efficacy. Conclusions: ZPHA-VRC NPs offer a safer and more effective delivery system for VRC, addressing the limitations of conventional formulations. The integration of alternative efficacy and safety models highlights their value in preclinical research.

Objective: To evaluate the bioequivalence of the two formulations of Eurofarma’s Levetiracetam 750 mg Extended Release Coated Tablets (Test Product [T]) against Keppra XR (Reference Product [R]) in healthy adults under fasting and fed conditions. Methods: The studies were designed as open, randomized, balanced, two treatments, two-period, single dose, crossover under fasting and fed condition with seven days washout interval. The assigned subjects were given test tablets and reference tablets in each period orally at a dose of 750 mg under fasting and fed conditions. Each study involved 32 subjects. In both the studies under fasting and fed conditions, the major pharmacokinetic parameters were calculated by SAS® Software 9.4 and the bioequivalence was evaluated. Results: For bioequivalence evaluation a total of 31 subjects completed the fasting study, and 29 subjects completed the fed study. The 90% confidence intervals for the geometric mean ratios of Levetiracetam area under the curve (AUC0-T and AUC0-∞) and maximum plasma concentration (Cmax ) were within the established bioequivalence limits of 80% to 125%. A total of three adverse events were reported during the conduct of the two studies, with one event possibly related to the study medication and the other two considered unrelated. All adverse events were mild to moderate in severity and did not significantly impact the participants’ quality of life. No serious adverse events were reported. Conclusion: It can be concluded that the two formulations can be used interchangeably.

Introdução. O levetiracetam é um antiepiléptico de segunda geração utilizado no tratamento de crises epilépticas, caracterizado por alta biodisponibilidade, farmacocinética linear, baixa ligação proteica e mecanismo de ação mediado pela proteína SV2A. Em fármacos de uso contínuo como os antiepilépticos, a demonstração de bioequivalência é essencial para garantir estabilidade de exposição sistêmica, segurança e intercambialidade terapêutica. No Brasil, Etira® 1000mg comprimido revestido é referência para levetiracetam, exigindo avaliação comparativa rigorosa conforme diretrizes da ANVISA. Objetivo. Avaliar a bioequivalência entre Levetiracetam 1000mg comprimido revestido (teste) e Etira® 1000mg (referência), administrados sob jejum em voluntários saudáveis. Método. Estudo aberto, randomizado, cruzado 2×2, dose única oral de 1000 mg após jejum mínimo de 8 horas. Concentrações plasmáticas determinadas por LC-MS/MS validado até 36 horas pós-dose. Parâmetros primários: Cmax e AUC₀–t. Bioequivalência demonstrada se IC90% das razões geométricas teste/referência estiver na faixa 80–125%, conforme diretrizes nacionais e internacionais. Resultados. Perfis de concentração plasmática comparáveis. Razões geométricas: Cmax 99,07% (IC90%: 92,95–105,58%) e AUC₀–t 101,41% (IC90%: 98,77–104,11%). Ambos parâmetros dentro da faixa regulatória. Formulações bem toleradas, sem eventos adversos graves. Conclusão. O medicamento teste demonstrou bioequivalência ao referência, suportando intercambialidade terapêutica e consistência biofarmacêutica.