Fed Gastric Dissolution Media: FeSSGF vs FEDGAS

Testing new or generic drug products in in vitro dissolution media that simulate in vivo gastric fluids after a meal can be very useful. Food changes the composition of these fluids greatly and this may have a big impact on how a drug behaves in the Fed State stomach.

FeSSGF Dissolution Medium

FeSSGF (Fed State Simulated Gastric Fluid), with its composition based on milk, has previously been proposed for dissolution testing but has distinct limitations:

*Fat content of FeSSGF is too low to replicate the fat content of an FDA meal  

*High variability and poor physical stability (see Figure 1) of the medium make the results difficult to transfer between labs  

*Only one pH is available so you cannot explore how drugs dissolve at different times within the fed stomach 

*Drug analysis is time consuming and requires extraction because FeSSGF blocks filters (unless filter diameter is large)

Figure 1 Physical stability of FeSSGF at t=0 and t=24 hours

Time after preparation (room temp)  t=0 hours  t=24 hours
Observation  Even immediately after preparation, instability is visible at the air/medium interface Separation of the medium is clearly evident
Filterability (via 0.45 micrometer glass filter with pre-filter)  Not possible to filter 1mL Not possible to filter 1mL

            

 

 

                                                                                                                                                                              

        

FeSSGF (pH adjusted to 4.5) at t=0 hours                         FeSSGF (pH adjusted to 4.5) at t=24 hours

FEDGAS Dissolution Media

Biorelevant.com has developed FEDGAS (Fed Gastric) dissolution media to overcome these limitations:

*900mL of FEDGAS has the full fat content of an FDA high-fat meal 

*The media possess consistent physicochemical properties and remarkable stability (see Figure 2) so results are reproducible and easily transferrable between labs 

*Three different pH values (pH6, pH4.5 and pH3) enable dissolution profiles to be established at different residence times in the fed stomach 

*Straightforward drug analysis after standard filtration through a 0.45 micrometer filter followed by standard HPLC                            

Figure 2 Physical stability of FEDGAS pH 4.5* at t=0 and t=24 hours

Time after preparation (room temp)  t=0 hours t=24 hours
Observation Medium is homogenous   Medium remains homogenous  
Filterability (via 0.45 micrometer glass filter with prefilter)  Easy to filter > 30mL  Easy to filter > 30mL 

 

 

 

 

 

 

 

*stability of FEDGAS pH6 and FEDGAS pH3 are both identical to FEDGAS pH4.5 

        

FEDGAS pH4.5 at t=0 hours                                          FEDGAS pH4.5 at t=24 hours

In summary, FEDGAS dissolution media simulate fed state gastric fluids after an FDA high-fat meal. They are simple to prepare, easy to filter and analyse, available at 3 different pHs and fully compatible with USP Dissolution Apparatus 2.