In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B(AmB),microemulsion vehicles composed of isopropyl myristate(IPM),Tween 80,isopropyl alcohol and water for transdermal delivery of AmB were designed.The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conducti-vities(σ).The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus.To obtain a high solubization of AmB,three different methods were tested to incorporate AmB into mi-croemulsion.The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature(PIT) of the emulsifier obtains the maximum drug content(2.96 mg/mL).The pH value of the system could be adjusted to pH>8.5 or pH<5.2,in this range AmB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets,drug precipitate is no more than 5%,and the formulations were corresponding to the characterizations of microemulsion.At pH 5.14,AmB microemulsion with Km 1:1,O/SC 1:9(mass ratio of oil phase to surfactant/cosurfactant blend),water content 64.6%,drug content(2.93±0.08) mg/mL,showed the maximum permeation rate(3.255±0.64) μg·cm-2·h-1,which is stable for a long time.
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机译：In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B(AmB), microemulsion vehicles composed of isopropyl myristate(IPM), Tween 80, isopropyl alcohol and water for transdermal delivery of AmB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conducti-vities(σ). The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into mi-croemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature(PIT) of the emulsifier obtains the maximum drug content(2.96 mg/mL). The pH value of the system could be adjusted to pH8.5 or pH<5.2, in this range AmB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1:1, O/SC 1:9(mass ratio ofoil phase to surfactant/cosurfactant blend), water content 64.6%, drug content (2.93±0.08) mg/mL,showed the maximum permeation rate(3.255±0.64)μg·cm-2·h-1,which is stable for a long time.
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