A novel in vitro release method for submicron-sized dispersed systems

Abstract

Sink conditions are often violated when using conventional release methods for dispersed systems. A novel reverse dialysis bag method was designed to overcome this problem. Model drug transport rates from submicron emulsions obtained using the conventional diffusion cell method and this novel method were compared. In the side-by-side diffusion cell method, emulsions were placed in the donor chamber and surfactant/buffer solutions in the receiver chamber. In the novel dialysis bag method, emulsions were diluted infinitely in the donor phase and surfactant/buffer solutions were placed in the receiver phase (dialysis bags). Slow release rates and linear release profiles were obtained using the side-by-side diffusion cell method apparently due to limited model drug solubility in the donor chamber resulting in violation of sink conditions. Biphasic release profiles were obtained using the dialysis bag method apparently due to an initial rapid release of free and micellar solubilized model drug from the donor to the receiver chambers followed by slow release from the oil droplets. Using both release methods, an initial increase and latter decrease in release rates were observed with increase in surfactant concentration. The initial increase was considered to be due to a decrease in the model drug oil-in-water partition coefficients and the subsequent decrease in release rates was due to micellar shape change (spheres to rods) causing a decrease in diffusion rates. Sink conditions were violated using the side-by-side diffusion cell method but were maintained in the dialysis bag method since emulsions were diluted infinitely in the donor phase.

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

“…26 Briefly, a preprepared CyA-loaded PCI micelle solution in phosphate/citrate buffer in phosphate buffered saline (pH 7.2) was directly placed into a 200 mL stirring sink solution in which numerous dialysis sacs containing 1 mL of the same sink solution were previously immersed. These sacs were equilibrated with the sink solution for ∼30 minutes prior to experimentation.…”

Mathematical modeling of surface-active and non-surface-active drug transport in emulsion systems

“…Model drug transport in emulsion systems can be affected by the presence of excess surfactant, as described elsewhere (16)(17)(18). The effective permeability coefficients of model drugs in emulsion systems are controlled by several mechanisms, such as the partitioning process between the oil, water, and micellar phases and membrane transport.…”

“…In addition, the Yoon and Burgess model and other previous models are limited because they are based on the use of side-by-side diffusion cell technique to determine the release rates of the model drugs from the emulsion systems. It has been shown that the side-by-side diffusion cell technique can lead to violation of sink conditions because of the limited membrane surface area available for transport compared with the interfacial area (16).…”

Performance Test for Parenteral Dosage Forms

“…At appropriate time intervals, one dialysis sac is removed, and the drug concentration is analyzed to calculate the percentage of release. This approach helps to maintain sink conditions because the formulation is diluted in the large volume of release medium outside the dialysis sacs (5,6,8). In addition, there are no problems of aggregation of the delivery system due to lack of direct stirring within the dialysis sacs (as can occur in standard [i.e., not reverse] dialysis methods).…”

“…Replenishing the medium at various stages of the test may be necessary to achieve sink conditions. When drug release is rapid, it may be impossible to maintain sink conditions within the dialysis sac, and as a result, the dialysis sac becomes a ratelimiting membrane (6,7).…”