RESUMO
Stearylamine, oleic acid, phosphatidylserine and dicetylphosphate have been studied to determine their capacity to induce electric charge on non-ionic submicron emulsions containing halofantrine and mefloquine. The in-vivo antimalarial activity of drug-loaded emulsions, evaluated in mice, was affected by the nature of the additives used. In particular, the electric-charge inducers markedly affected the pharmacological activity of mefloquine, but not of halofantrine. After subcutaneous administration ED50 values (the doses affording 50% protection) were 3 and 15 mg kg(-1), respectively, for halofantrine and mefloquine emulsions without charge inducers. The mefloquine-loaded emulsions with charge inducers were active at 10 mg kg(-1) for dicetylphosphate, 17 mg kg(-1) for phosphatidylserine, 23 mg kg(-1) for oleic acid and 27 mg kg(-1) for stearylamine, again after subcutaneous administration. This work has enabled the formulation of stable emulsions, incorporating drugs with high antimalarial activity, which are proposed for parenteral delivery of these fairly soluble drugs.
Assuntos
Antimaláricos/farmacologia , Excipientes/farmacologia , Mefloquina/farmacologia , Fenantrenos/farmacologia , Eletricidade Estática , Animais , Interações Medicamentosas , Estabilidade de Medicamentos , Emulsões , Íons , Masculino , CamundongosRESUMO
Several oil-in-water submicron emulsions stabilized with unsaturated and saturated lecithins or non-ionic surfactants and were prepared in presence of various tonicity agents and related substances used as cryoprotectants. Their physical properties before and after thermal stress was investigated. Egg yolk lecithins required glycerol as tonicity agent when the emulsions will be heated, while soy bean lecithin stabilized emulsions could be isotonized by various non-electrolytes. The addition of co-surfactants e.g. oleic acid and deoxycholic acid did not improve the heat resistance of emulsions prepared with egg yolk lecithin and sorbitol.
Assuntos
Emulsões/química , Fosfatidilcolinas/química , Tensoativos/química , Fenômenos Químicos , Físico-Química , Excipientes , Concentração de Íons de Hidrogênio , Lipossomos , ReologiaRESUMO
Phenyl-substituted normethadone derivatives were synthesized and their affinity (IC50) for opioid receptors was determined by displacement of the specific binding sites of [3H]sufentanyl on rat brain preparations. Substitution resulted in a decrease of affinity in-vitro. These results suggest that normethadone-like compounds may interact with the P subsite of the mu-opioid receptor and that the P subsite has a well-defined cavity shape of stringent dimensions.
