Pharmaceutical Manufacturing Handbook: Production and

M A DCt t = ⎡ ε s
( 2C − C ) ⎤
0 ε s
⎣⎢ τ
⎦⎥
INSOLUBLE MATRIX TABLETS 1199
The most common types of insoluble matrix tablets are those containing pores.
From the equations above one can see that the drug - release depends on the solubility
of the drug, the drug - loading concentration, and the diffusion coeffi cient, which
is related to the molecular size of the drug. The area of the insoluble matrix tablet
also affects the drug release and can be changed by altering the dimensions or the
geometry of the tablet. The drug release from insoluble matrix tablets also depends
on the porosity and pore structure of the tablet, and the drug release rate increases
with increasing porosity.
A comparison of Equations (3) and (4) shows that, in both equations, the amounts
of released drug are directly dependent on the area of the device, the square root
of the time t , the drug - loading concentration C 0 , the respective saturated drug concentrations,
and the drug diffusion coeffi cients. In addition, the release rate (the
time derivate of the amount of released material) depends on the square root of
time and can be stated as
05 .
(4)
dMt
1
∝ (5)
dt t
As pointed out above, for ideal ER formulations, the rate - limiting step for drug
absorption is the release rate from the ER formulation. Thus, since the release rate
from an insoluble matrix system depends on time, the concentration of drug in the
blood plasma will also be time dependent and not constant (Figure 2 ), which may
be a therapeutic drawback. Another factor infl uencing the concentration of drug in
the blood plasma is the gastrointestinal transit times. When the transit times of the
formulations vary, the reproducibility between different administration occasions
in one patient will be low, and furthermore, great variation in the patient group
may be obtained. However, these conclusions are valid for all ER formulations
based on matrix systems and not limited to insoluble matrix systems only.
The equations above are valid when no depletion of drug occurs inside the
device. The equations for release rate will be much more complex when depletion
of the drug can occur [30] . However, it has been shown that, when the amount of
released material is less than approximately 60%, the release rate will depend on
− 0.5 time as t [29, 30] .
6.8.2.2 Manufacturing of Insoluble Matrix Tablets
Insoluble matrix tablets need a carrier, which can be a lipid - or polymer - based
excipient [7, 31 – 36] . Some suggestions of carrier materials can be found in Table 1 .
The table also presents the number of hits found upon searching the FDA ’ s homepage
[37] for the number of times an excipient is registered as a component in oral
extended, sustained, or controlled formulations. This list gives an indication of how
often these excipients are commercially used in oral ER formulations but does not
automatically tell us the exact formulation or exact mechanistic effect of the excipient.
The choice of carrier material is important, and one should be aware of possible