| dc.description.abstract | Tablets are one of the most preferred dosage forms for patients, but pre-formulation studies for
tablets are often time consuming and expensive. The SeDeM Expert Diagram System attempts
to address this problem by decreasing the amount of experiments required to develop an
acceptable direct compression tablet formulation. This is done by processing and interpreting
data obtained from known techniques already widely in use in the pharmaceutical industry to
characterise active pharmaceutical ingredients (API’s) and excipients. In this study, the prediction
ability of the SeDeM Expert Diagram System with a special focus on testing the limits of the
system was investigated.
Three different API’s with different direct compression properties (i.e. paracetamol, furosemide
and pyridoxine) as well as seven excipients representing different classes and types of widely
used direct compression excipients (i.e. Tablettose® 80, FlowLac® 100, Avicel® PH200,
Emcompress®, Cellactose® 80, MicroceLac® 100 and StarLac®) were selected and characterised
by applying the SeDeM Expert Diagram System. Predicted formulations were tableted and
evaluated according to the set criteria. If a tablet formulation failed to meet the criteria, the ratio
of excipient to API was increased in 5 % w/w increments until a successful formulation was
obtained, whereas the reverse was applied if a formulation was successful to determine failure
point.
The SeDeM Expert Diagram System proved to be proficient at predicting acceptable tablet
formulations, with a few exceptions. This was specifically the case where paracetamol and
furosemide were concerned as well as some excipients. While SeDeM predicted that
paracetamol would only be able to deliver acceptable tablets with three excipients (i.e.
FlowLac® 100, Avicel® PH200 and StarLac®), all the selected excipients were in fact able to create
acceptable direct compression tablets. When all the paracetamol formulations were considered,
tablet failure most often occurred due to capping. However, the reason for failure of the novel
direct-compression excipients (i.e. Cellactose® 80, MicroceLac® 100 and StarLac®) was due to
problems other than capping.
In the case of furosemide, the limits of five parameters were not met, including particle size limits,
powder flow as well as the cohesion index. The SeDeM System was unable to successfully
predict any furosemide direct-compression tablet formulations because the powder mixtures
exhibited poor powder flow properties. This can be explained by the fact that furosemide has very small particles, which coated the excipient particle surfaces and thereby formed interactive
powder mixtures, which was confirmed with the use of SEM microscopy.
SeDeM was able to correctly predict five of the seven selected excipients for successful directcompression
tablet formulations for pyridoxine within an acceptable margin of error. Only two
excipients (Emcompress® and Cellactose® 80) performed better than expected by the SeDeM
System.
From the results of this study it is evident that certain physicochemical properties of API’s such
as elasticity and cohesive behaviour are not compensated for or compensated for sufficiently by
the SeDeM System. Furthermore, some novel direct-compression excipients (e.g. co-processed
excipients) proved to exceed the SeDeM Expert Diagram Systems’ expectations and predictions
to correct for API failure to produce direct compressible tablets | en_US |
