PHARMA FOCUS//Drug FOCUS Formulation & Design
How to prevent potential drug-polymer interactions Thorsten Agnese and Thorsten Cech of BASF SE’s European application lab for pharma solutions investigate the benefits of delivering gastric-resistant functionality to a tablet, by applying a colourless top coat based on Kollicoat MAE 30 DP.
I
n the field of gastricresistant film-coating, a lot of obstacles can occur during formulation development. Some
pharmaceutical actives, such as
values were recorded as L*a*b* values
Table 2: Set-up coating trials
of the CIELAB colour space.
Sub-coat Top coat Batch size
4.0kg
4.0kg
12rpm
12rpm
65°C
55°C
To compare the effect of the MAE top coat on the hue, the colour reading of the sub-coated tablet was
omeprazole, are prone to interactions
Drum speed
with the functional polymer poly
Inlet air temperature
(methacrylic acid-co-ethyl acrylate)
Inlet air quantity
450m³/h
450m³/h
appraisal was done on the basis of the
(MAE). Yet, one should consider
Spray rate
13g/min
13g/min
delta E value (see Figure 1).
that the coating material itself is
Atomising pressure
1.8 bar
1.8 bar
also vulnerable to interactions with
Pattern air pressure
1.8 bar
1.8 bar
excipients, like pigments or colourants present in the coating formulation. This
Coating process
work was set to investigate whether the
For coating equipment, the XL Lab
gastric-resistant functionality can be
01 (Manesty) was used. The coater
applied to a colourless film, coated
was assembled with a mid-sized drum
onto a tablet bearing a coloured
480mm in diameter. For the nozzle, the
instant-release sub-coat.
OptiCoat gun with an orifice diameter of 0.8mm was used.
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25
20
MAE was applied as top coat with
forming polymer. For the sub-coat,
6mg/cm², 8mg/cm² and 12mg/cm².
seven Kollicoat IR- (BASF) based ready-
The test was conducted with various
to-use coating systems with different
amounts of plasticiser (see Table 3).
Ludipress LCE
74.0
Kollidon CL-F
5.0
Kollidon VA64 fine
5.0
Mg-stearate
0.5
% present in the coat
schema (see Table 2). five coating levels: 3mg/cm², 4mg/cm²,
15.5
% related to the polymer content
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selected for the gastric-resistant film-
Caffeine, gran. 0.2-0.5
Plasticiser content
20
citrate (TEC) (Jung-bunzlauer) were
Quantity (%)
Table 3: Plasticiser content in the top-coat formulations
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combination with the plasticiser triethyl
Ingredients
(Rhopoint Instruments).
diameter, were coated according to
Kollicoat MAE 30 DP (BASF), in
Table 1: Composition of the cores
The gloss value (n=5) was determined using a Novo Curve 60°
9
Round-shaped tablets, 8.0mm in
gain of 3.5%.
different top coats (see Table 3). The
10
Materials and methods
colours were applied, with a weight
compared with those bearing the
Dissolution testing
Figure 1: Equation for calculating the ∆E-value
The dissolution test (n=3) was
Results and discussion
conducted for the first two hours at pH
Seven batches were coated, each
1.1 (HCl, 0.08mol/ℓ; volume 880mℓ)
with one base colour. After uniting all
and 37°C (+ 1K). The paddle speed
tablets, every individual batch used
was set at 50rpm. By adding 20mℓ of
for the top-coat trial bore an equal
a concentrated sodium phosphate
number of tablets of each colour.
buffer system, the pH value was
TEC was chosen as a highly suitable
adjusted to 6.8 for an additional
plasticiser for MAE in this investigation1.
60 minutes. The drug release was
Four different top-coat formulations
determined photometrically via
were applied (see Table 3 and
online measuring.
Figure 2). The plasticiser level of 10% was the
Colour and gloss measuring
only one that resulted in a brittle film
used for the core formulation: caffeine
For colour measuring (n=10) the
showing cracks immediately after the
gran. 0.2 to 0.5 (Siegfried); Ludipress
Datacolor 400 (Datacolor) was used.
coating process (see Figure 3). All
LCE; Kollidon CL-F; Kollidon VA64 (all
The experimental setup was as follows:
the other concentrations were found
BASF SE); and magnesium stearate
aperture USAV; light source D65 and
to be suitable. Interestingly, even
(Baerlocher). See Table 1.
observe angle 10°. The colourimetric
though it was used with a maximum
The following components were
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| MAY 2020 | P C Review
