RESUMO
To obtain a sustained fentanyl delivery with effective and precise control, fentanyl loaded wafer was fabricated using poly(L-lactide-co-glycolide) (PLGA) oligomer by direct compression method. XRD and DSC analysis indicated the presence of crystalline drug in the wafers. The release of fentanyl from PLGA wafer was determined to be primarily diffusion controlled, but swelling and erosion also contributed to the release process. In vitro release studies showed that different release patterns and rates could be achieved by simply modifying factors in the preparation conditions. The wafer degradation profiles were also investigated to understand the drug release mechanism. Gravimetric studies of mass loss of wafers during the incubation revealed that the weight loss increased apparently after 4 days. These results indicate that the polymer degradation was contributed to drug release followed by diffusion. From the results, this constant localized release system can potentially provide anesthesia for a longer period than injection or topical administration.
Assuntos
Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Lactose/análogos & derivados , Metilcelulose/análogos & derivados , Materiais Biocompatíveis , Varredura Diferencial de Calorimetria , Cromatografia Gasosa , Cristalografia por Raios X , Portadores de Fármacos , Cinética , Ácido Láctico , Microscopia Eletrônica de Varredura , Oxazinas , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , Solubilidade , Água/químicaRESUMO
We developed several kinds of fentanyl-loaded poly(L-lactide-co-glycolide) (PLGA) microspheres (FMS) for sustained release of fentanyl. FMS were prepared by an emulsion solvent-evaporation method. In this study, the influences of several preparation parameters, such as initial drug loading, polymer concentration, and solvent volume on the release patterns of fentanyl were investigated. Furthermore, it has been well noted that the detection of fentanyl is extremely difficult because its clinical dose level is very low, about 1-3 ng/ml, in cancer-patient treatment. Therefore, we also developed a rapid and sensitive determination method for fentanyl in systemic circulation by employing gas chromatography (GC) system. Fentanyl was slowly released from FMS over 15 days with a quasi-zero order property. From the results, our FMS may be good formulations to deliver the analgesics and suitable for the treatment of severe pain over long periods.