Reciprocating cylinder method and flow-through cell method are commonly used in the study of drug release in vitro. They can simulate the changing physiological environment in human gastrointestinal tract by changing various dissolution media during the experiment. Therefore, some literatures will call them "biological related methods"
However, the structural and design differences between the two methods determine that the test samples will face two different fluid states, which will eventually affect the experimental data. This paper will analyze the difference between the reciprocating cylinder method and the flow-through cell method by comparing the test results of the in vitro release of a sustained-release preparation.
Experimental Method
In order to control the variables in the test process, the experimental parameters of the two methods will be consistent as much as possible. For example, both the reciprocating cylinder method and the flow-through cell method use the same sampling time point and dissolution medium. In addition, the volume of 250ml dissolution medium used in the reciprocating cylinder method can meet the sink condition. Due to the technical confidentiality agreement, the key parameters of the experimental method will be omitted in this paper.
Reciprocating Cylinder（USP Apparatus 3)
Dissolution system: Raytor RT3-AT reciprocating cylinder automatic sampling dissolution system
Volume of dissolution medium: 250 mL
Temperature: 37.0 ± 0.5 ℃
Flow-Through Cell Method（USP Apparatus 4)
Dissolution system: Raytor RT7 flow-through cell dissolution system
Flow-through cell: 22.6mm inner diameter large cell
Temperature: 37.0 ± 0.5 ℃
A 5mm diameter ruby ball is placed at the bottom of the flow-through cell and filled with 1mm diameter glass beads.
In Vitro Release Results
Reciprocating Cylinder Test Result
Because the reciprocating cylinder method has greater fluid shear force, the reference and self-developed samples have been basically released in 10 hours. The RSD of the final dissolution rate of the reference was 1.6%, and that of the self-developed sample was 2.3%. The repeatability of the test results was good. The final dissolution rate of the self-developed sample was slightly lower than that of the reference.
Flow-Through Cell Test Result
The samples tested by flow-through cell method were fully released in nearly 20 hours, which was more in line with the design expectation of 24-hour sustained release of the drug. The RSD of the final dissolution rate of the reference was 1.4%, and that of the self-developed sample was 2.8%. The repeatability of the test results was good. It can also be observed that the final dissolution rate of the self-developed sample is lower than that of the reference.
Result Discussion
Although both test methods can show that the final dissolution rate of the self-developed sample is lower than that of the reference, the flow-through cell method is obviously better than the reciprocating cylinder method in terms of method discrimination. The test results of flow-through cell method can more obviously show the difference between self-developed samples and reference in the whole drug release process.
Thanks to the gentle constant velocity laminar flow in the flow-through cell, the drug can be released in vitro in a fluid environment closer to the gastrointestinal tract, which is easier to reflect the impact of changes in production process and prescr1ption on drug release.
The reciprocating cylinder method can provide greater fluid shear force and significantly accelerate the drug release rate. While shortening the experimental time, it will sacrifice the discrimination of the method to a certain extent. Reducing the reciprocating rate can reduce the fluid shear force, but the experimental data shown that even under the condition of very low reciprocating rate (e.g. 5 DPM), the fluid shear force generated by it is still higher than that under the high flow rate of flow-through cell method.
According to the characteristics of high shear force, the reciprocating cylinder method is more suitable for accelerated experiments of long-term in vitro release determination, such as implants. Through the greater fluid shear force than the paddle /basket method and the flow-through cell method, the drug release process is accelerated and the experimental time is shortened. In addition, the reciprocating cylinder method is also suitable for the study of the release of chewable tablets: glass beads are filled in the reciprocating cylinder with up and down reciprocating motion to simulate the chewed state of tablets in the mouth.
The flow-through cell method and the reciprocating cylinder method have their own characteristics. We should choose the appropriate determination method according to the experimental purpose, so that the test results can meet our expectations.