| Revista: | Anais da Academia Brasileira de Ciencias |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000436064 |
| ISSN: | 0001-3765 |
| Autores: | Abrahim Vieira, Barbára A1 Souza, Alessandra M.T. de1 Barros, Rita C1 Carmo, Flávia A. do1 Abreu, Letícia C.L. de1 Moreira, Ronyson S.S1 Honório, Thiago S1 Rodrigues, Carlos R1 Sousa, Valeria P. de1 Cabral, Lucio M1 |
| Instituciones: | 1Universidade Federal do Rio de Janeiro, Departamento de Farmacos e Medicamentos, Rio de Janeiro. Brasil 2Instituto Federal de Educacao, Ciencia e Tecnologia do Rio de Janeiro, Direcao de Ensino, Duque de Caxias, Rio de Janeiro. Brasil |
| Año: | 2020 |
| Volumen: | 92 |
| Número: | 2 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | Sildenafil is a potent selective inhibitor of phosphosdiesterase-5 previously used in erectile dysfunction and subsequently approved in 2005 for pulmonary arterial hypertension treatment. Since oral administration of sildenafil shows pharmacokinetic problems with mean absolute bioavailability of 41%, the goal of this work was to develop a novel sildenafil self-emulsifying drug delivery system (SEDDS) for oral absorption improvement and management of dosage. One pharmaceutical solution and four SEDDS containing sildenafil were successfully obtained and SEDDS formed O/W nanoemulsion with droplet size less than 300 nm. The stability studies evidenced that the SEDDS containing 3.3% w/w of sildenafil yielded the best results. The safety of 2-pyrrolidone/isobutanol in oral formulations was assessed in mice and no lethality was achieved in the placebo groups with LD50 of 490 mg/Kg for SEDDS II-3.3, suggesting it as a safe excipient for humans. Therewithal, in silico studies using PBPK models provided the pharmacokinetic profile of sildenafil SEDDS. Subsequently, in silico evaluation indicated that the sildenafil SEDDS droplet size influenced its bioavailability, enhancing absorption, assuring a good pharmacokinetic profile. These findings suggest that the formulations developed here presented the potential to enhance drug oral absorption with the possibility to control drug dosage as they are liquid pharmaceutical formulations |
| Disciplinas: | Medicina |
| Palabras clave: | Farmacología, Química farmacéutica, Sistema cardiovascular, Sildenafil, Sistemas de liberación de fármacos, Auto-emulsificación, Hipertensión arterial pulmonar |
| Keyword: | Pharmacology, Medicinal chemistry, Cardiovascular system, Sildenafil, Drug delivery systems, Self-emulsification, Pulmonary arterial hypertension |
| Texto completo: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
