The release and analgesic activities of morphine and its ester prodrug, morphine propionate, formulated by water-in-oil nanoemulsions.

摘要

In this study, we examined the feasibility of water-in-oil (w/o) nanoemulsions as sustained-release systems for morphine, following subcutaneous administration in rats. The ester prodrug of morphine, morphine propionate (MPR), was also utilized in this study. A variety of nanoemulsions were prepared using soybean oil or sesame oil as the external phase. Span 80, Tween 80, Plurol diisostearique and Brij 98 were used as surfactants in the w/o interface. The effects of the formulation variables on the characteristics of the nanoemulsions, such as inner droplet size, zeta potential, viscosity, drug partitioning, drug release and pharmacological effect, were evaluated. Mean sizes of nanoemulsions of 50-200 nm were obtained. The initial surface charge of the emulsions was found to be around - 3 to - 4 mV, except that the Plurol-containing vehicle showed a highly negative charge of - 23 mV. The loading of morphine and MPR into the nanoemulsions resulted in slower sustained-release behavior as compared with the drug/prodrug in aqueous solution. The rate of morphine released across the membrane was found to be highly dependent on the choice of oil and surfactant types. On the other hand, discrepancies in MPR release rates among the various formulations were minimal. The in vivo analgesic duration of morphine by targeting the drug to central nerve system could be prolonged from 1 to 3 h by incorporating the drug into nanoemulsions using Span 80 or Tween 80 as the surfactant. These results suggest that w/o nanoemulsions are well suited to provide sustained morphine delivery for therapeutic purposes.