The following article has been authored by John Heaney.
Like the reciprocating cylinder (Apparatus 3), the flow-through diffusion cell (Apparatus 4) is quite rare compared to baskets (Apparatus 1) and paddles (Apparatus 2). But there are some distinct advantages to flow-through cell that can make it a boon to certain formulations.
The design of the flow-through cell consists of a cell with specific dimensions with the dissolution media fed through it by a pump. The dissolution media is typically stored in a reservoir. The media can be recirculated which is referred to as a closed-system; or constantly dispensed and collected referred to as an open-system. The cell may have different items used with it to change the behavior of the media as it is pumped through. A tablet holder to suspend the tablet in the cell is one such option. Glass beads in the bottom of the cell to produce a more uniform, or laminar flow of media through the cell is another.
Just like switching between baskets and paddles, these items can change the hydrodynamics around the tablet and affect the dissolution rate. The glass beads will produce a laminar flow, so there is not much mixing within the cell and the flow is more uniformly spread out within it. Conversely, having the tablet sit in the bottom of the cell without glass beads may result in more turbulent flow which may result in the tablet dissolving faster. The tablet holder can be used with or without the glass beads depending on the needs of the method.
The flow-through cell excels for formulations which are in BCS class IV which generally have low solubility and low permeability. The ability to run the system in an open or closed state allows the sink conditions to be adjusted without changing the media composition. In addition, the constant flow of media allows for easier pH changes compared to Apparatus 1 and 2 where the vessel would need to be drained and/or switched with different dissolution media.
Dissolution methods developed on the flow-through cell cannot be transferred to Apparatus 1, 2 or 3. The devices are simply too different to allow for any kind of method compatibility.
The Flow-Through Diffusion cell, while rare, can be of significant benefit for groups looking to develop dissolution profiles for BCS class IV compounds or extended-release compounds that require pH changes.
· Basic design
o Pump feeds media through a vessel/cell
o Can be open (like ILC07) or closed (recirculating)
o Different vessels/cells available depending on needs
o Different ways to have tablet
§ Holder
§ On glass bead bed
§ On check-valve/ruby bead
§ Depends on desired flow around tablet
o Easy pH changes by swapping media
o In through bottom out through top pumping makes air bubbles easy to remove
o Potentially large volumes ideal for poorly soluble drugs
o Laminar vs Turbulent flow
§ Layers move past without mixing much, low friction on tablet
§ Rapid movement in may directions, lots of mixing, may erode tablet faster
§ App 4 can be either depending on setup
· Glass beads = laminar
· Variables
o Flow rate
o Temp
o Glass beads
§ Amount
§ Size
o Tablet placement
o Closed and Open Loop
§ Closed can get down to low volumes around 100 mL
§ Open can be nearly infinite