Emulsion is an immiscible two-phase liquid, in which one phase is dispersed in the other phase in the form of small droplets. It is a non-uniform dispersed liquid preparation, which can be used for injection, oral administration and local administration.
In vitro release is an important quality control index of emulsion, but the traditional dissolution method is difficult to meet the test requirements of in vitro release of emulsion: on the one hand, because the particle size of emulsion is small, the traditional dissolution method is difficult to separate the released API from the emulsion particles; On the other hand, the solubility of some drugs is relatively low, so it is difficult for the samples to be in the sink condition in the process of in vitro release.
At present, many research literatures suggest that more modern methods can be used to determine the in vitro release of emulsion, such as flow-through cell method, dialysis method, sampling-separation method and so on.
Among them, dialysis method may have the problem of very slow release rate (research shows that the release rate of emulsion determined by dialysis method is much slower than its real release rate in human body); The difficulty of sampling-separation method is how to effectively separate released API and emulsion particles, and the operation of this method is complex.
As an alternative, the filtration system of flow-through cell method can separate the released API and emulsion particles without the problem of too slow release rate of dialysis method. This article will share the case of in vitro release determination of an emulsion, hoping to bring you help and inspiration.
Experimental Method
Flow-Through Cell Method（USP Apparatus 4)
Dissolution System: Raytor RT7 Flow-Through Cell Dissolution System
Flow-Through Cell: Technical Confidentiality
Test Parameters: Technical Confidentiality
Sampling Time: 2.5，5，7.5，10，15，20 min
Experimental Result
Cumulative dissolution curve of Sample 1:
Cumulative dissolution curve of Sample 2:
The dissolution curves of Sample 1 and Sample 2 fit well, and the relative standard deviation (RSD) of the final dissolution rate are 0.54% and 0.79% respectively. The determination method has good repeatability.
By comparing the average dissolution curves of the two samples, it can be found that the in vitro release rate of Sample 2 is faster than that of Sample 1. This method has good discrimination.
Result Discussion
The test results of this case show that the flow-through cell method can effectively determine the in vitro release of emulsion. Especially for some emulsion products with fast release speed, the flow-through cell method has shorter sampling interval and more accurate test results than dialysis method and sampling-separation method.
In addition, in the process of method development, whether the dissolution medium meets the sink condition is also the key point to be concerned. The slow release rate of dialysis method is often caused by the failure of this test method to meet the conditions of sink condition.
After the emulsion is added into the dialysis bag, the volume of dissolution medium in the dialysis bag is limited, and in most cases it will not reach the sink condition. At this time, most drugs are still in the oil phase particles, and only a few API can be released into the water phase, and the release process is relatively slow. In addition, the contact area of the emulsion release process is only the surface area of the dialysis bag, which is much smaller than the total surface area of the dispersed particles in the emulsion. The low concentration of the initial aqueous phase drug and the small release contact area eventually lead to the slow and incomplete release of the emulsion sample.
In addition, there is also an upper limit on the volume of dissolution medium in the sampling-separation method, while there is no upper limit in theory for the volume of dissolution medium in the flow-through cell method. Therefore, under the same test conditions, the flow-through cell method can obtain better sink conditions than dialysis method and sampling-separation method, and is more suitable for the determination of in vitro release of emulsion containing insoluble drugs.