RESUMO
A novel lipid formulation containing fenofibrate in omega-3 oil was developed using a novel high-throughput screening platform. The optimized formulation combines the cardiovascular health benefits from omega-3 oil with the potent lipid-regulating effect of fenofibrate. When tested against the current marketed product Tricor in healthy human volunteers, the new formulation was shown to be equivalent to Tricor.
Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Ácidos Graxos Ômega-3/química , Fenofibrato/química , Hipolipemiantes/química , Administração Oral , Área Sob a Curva , Química Farmacêutica/instrumentação , Estudos Cross-Over , Estabilidade de Medicamentos , Emulsões , Excipientes/química , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacocinética , Fenofibrato/administração & dosagem , Fenofibrato/farmacocinética , Meia-Vida , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/farmacocinética , Estrutura Molecular , SolubilidadeRESUMO
Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex(R) showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro-in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a 'spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors ('parachutes') were shown to provide both enhanced dissolution and high oral bioavailability.