Calcium Phosphate Excipients - Innophos

% Water
15
10
5
Moisture
Figure 9:
Equilibrium Moisture Isotherms, 25°C
0
0 20 40 60 80 100
% Relative Humidity
TRI-TAB ®
A-TAB ®
DI-TAB ®
Equilibrium moisture adsorption isotherm at 25°C expressed as %
water on an anhydrous basis vs. relative humidity. Moisture determined
for A-TAB ® and TRI-TAB ® at 105°C; for DI-TAB ® at 60°C.
While TRI-TAB ® is slightly hygroscopic and may
pick up surface moisture or contain moisture
in small pores, it does not form a well-defined
crystalline hydrate, and surface moisture can be
readily removed in an oven. The moisture content
of TRI-TAB ® can be determined by drying at 105°
and is typically about 0.2%. High temperatures
(>100°C) can also be used to determine the
surface moisture of A-TAB ® , because A-TAB ® is
an anhydrous material. Unlike A-TAB ® , moisture
determination or weight loss-on-drying for DI-TAB ® ,
dicalcium phosphate dihydrate, is done at 60°C.
At higher temperatures, some of the waters of
hydration of DI-TAB ® are removed, leading to
incorrect high surface moisture values.
When DI-TAB ® or powdered dicalcium phosphate
dihydrate is dehydrated, it cannot be rehydrated
again to form the dihydrate. Thus, a formulation
exposed to high temperatures, say 50° or 60°C,
can irreversibly lose water.
The anhydrous dicalcium phosphate salt will not
pick up water to form the dihydrate because it
is a thermodynamically stable material. In a wet
granulation, the anhydrous remains anhydrous
as shown by its X-ray diffraction powder pattern.
Compatibilities and Stability
A well-known incompatibility for calcium salts
is with the tetracycline antibiotics. These drugs
should not be taken within two hours of eating
dairy products such as milk, yogurt or cheese,
or taking calcium or iron supplements.
Hydroxyapatite is incompatible with tocopheryl
acetate (but not with tocopheryl succinate). The
reason is attributed to the large number of hydroxyl
groups on the hydroxyapatite surface and the large
surface area of this excipient.
DI-TAB ® , which contains waters of crystallization,
is stable during storage under normal conditions
(20° – 40°C). However, some of this water can be
lost during storage at higher temperatures and
may interact with water-sensitive ingredients in a
formulation. Accelerated stability testing of tablets
containing DI-TAB ® Should not be done at high
temperatures of 50° – 60°C, as they will yield
erroneous results. This can give rise to some
apparent incompatibilities at higher temperatures,
where the released moisture may interact with
drugs, vitamins and other excipients. To extrapolate
such findings to room temperature would be
erroneous, since dicalcium phosphate dihydrate
does not dehydrate at this temperature.
Arrhenius plots should not be done for dicalcium
phosphate dihydrate dosage forms which have
been stored under high temperature conditions
because the dihydrate may no longer be present.
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