Research paper
Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation model

https://doi.org/10.1016/0378-5173(90)90381-DGet rights and content

Abstract

The in vitro release of diazepam from a submicron o/w emulsion was evaluated using the dialysis bag technique diffusion and the bulk-equilibrium reverse dialysis bag technique. Irrespective of the nature of the sink solution used, the release rate of diazepam from different emulsion dosage forms remained slow and incomplete as compared to a diazepam hydroalcoholic solution using the dialysis bag technique. This was attributed to a marked decrease in the aqueous drug gradient of drug available for membrane diffusion in the presence of the oily internal phase, rendering the permeation through the dialysis membrane the rate-limiting step in the overall kinetic process. It can definitely be deduced that the dialysis bag technique could not be considered an appropriate method to evaluate the true release mechanism of a drug from a colloidal carrier. An in vitro kinetic model is therefore proposed where the colloidal drug carrier suspension is directly placed in the release solution and has the opportunity to release the drug content under maximum dilution and perfect sink conditions. The drug released sampling is performed through immersed dialysis bags previously filled and equilibrated with the sink solution in the receptor compartment. The release profiles of diazepam from the actual submicron emulsion was similar to that observed from marketed aqueous and emulsion dosage forms correlating well with pharmacokinetic results reported in the literature. It was found that the release rate from the oily nanodroplets was faster than the permeation rate through the dialysis membrane which should be the slowest step governing the overall kinetic process despite rapid and complete diffusion of dissolved drug within less than 1 h. In view of the overall results it can be concluded that the release of diazepam from submicron emulsion is very rapid under perfect sink conditions.

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