Novel modified vertical diffusion cell for testing of in vitro drug release (IVRT) of topical patches

New vertical diffusion cell designs for bubble-free in vitro drug release tests


Donor Chamber volume90 mL
Buffer Tank volume25 mL
Receptor/Acceptor Chamber53 mm; 50 mL
Stub Diameter4–5 mm
Double-Walled Tankinternal floor area: 65 mm
height: 50-60 mm
Semi-Permeable Membrane cellulose-based membrane or heat-crosslinked polyvinyl alcohol membrane
Flow Rate50 ml to 100 ml/min
Silicone Insert40 mm x 40 mm x 3 mm
Glass Plate30 mm x 30 mm x 2 mm
Hamilton Syringe0.5 mL or 1.0 mL
PVA Scaffold average diameter: 0.5 ± 0.1mm
Drug Recovery97% to 108%
RSD < 2.4%
Drug Release70–73% at 240 min


This tech spec was submitted by Romána Zelkó as part of the University Technology Exposure Program.

Problem / Solution

Topical semi-solid formulations in vitro release studies are necessary for formulation development, manufacturing process validation, batch testing validation, and drug therapeutic efficacy verification. Franz vertical diffusion cell is the most commonly used instrument for these studies for release and permeation tests. Its advantage is that it can be used as a stand-alone device, be partially automated, and operate up to 6 vessels in parallel. However, keeping the cells free of bubbles during sampling is challenging. Bubbles can lower the reproducibility and representativeness of the assay by disrupting the measurement cycle.

 The redesigned static vertical diffusion cell mainly consists of an acceptor and a donor component. The donor component is where an inert mixer provides the mechanical agitation required for drug release. The acceptor side remains bubble-free by simultaneous replenishment of liquid sample with the same volume as the amount sampled without automating the system.


 There are two proposed models. The first modified vertical diffusion device consists of three main glass components: donor chamber, receptor/acceptor chamber, and buffer tank. The second modified vertical diffusion device consists of two additional features: a double-walled tank of the primary water jacket and a thermocouple sensor.

The donor chamber receives a sample from the external environment, while the receptor chamber is for drug release and diffusion. In comparison, the butter tanks replace receptor fluid and equalize its volume.

The double-walled tank is a glass vessel containing water as a heating medium with a diffusion cell or the thermostatic sensor to ensure a constant temperature of the receptor fluid. The thermocouple sensor controls the temperature.

A ball joint clip encloses the sample to be tested by securing the donor chamber and the receptor chamber. A cellulose-based semipermeable membrane is placed in opposite directions. In addition, a silicone insert and glass plate can be inserted between the donor chamber and the receptor chamber, depending on the type of sample used.

The receptor chamber made from a three-necked, round-bottomed flask has a larger volume and spherically symmetrical geometry than the Franz model. The increased acceptor side volume allows for a greater number of samples to be processed without a significant decrease in concentration. The drip funnel (buffer tank), the sampling syringe, the thermocouple, and the donor chamber are connected to the receptor chamber with threaded nozzles.

Different threaded nozzles are used on the receptor chamber walls of the first and second models. The nozzle of the first design can be closed with a glass pin and helps to fill the system without bubbles. Hence, making it not suitable for receiving the temperature control unit. The nozzle of the second model has the temperature control sensor immersed in the receptor fluid. This more extended nozzle has a liquid-tight membrane and a cap that can be sampled and closed with a water-tight seal. 

The receptor reservoir wall has an additional three cylindrical abrasive-tipped nozzles with receptor fluid to act as a dropping additional funnel and buffer reservoir. The drip funnel and inlet nozzle have glass taps to separate the liquid parts from each other as needed temporarily. A magnetic stirrer at the bottom of the set-up and stir bar inside the chamber is used to provide acceptor fluid agitation. In addition, a Hamilton syringe is used for sampling and is attached to an inlet.

In the first simpler model, the diffusion cell is immersed in and heated by the water-filled glass vessel that acts as the tempering medium with the temperature control unit. It is controlled by the heated magnetic stirrer while stirring the acceptor fluid.

While in the second design, the diffusion cell is immersed in the double-walled glass vessel in which the secondary water jacket is located. The primary water jacket circulating in the double-walled vessel provides the heat exchange needed for the secondary water jacket. A water bath or a separate magnetic stirrer can heat the primary water stream.


A research paper describing the challenge, design, and outcome of the research

István Sebe, László Zsidai, Romána Zelkó

Wevolver 2023