Beruflich Dokumente
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1. Principle
2. Important Hints
Sealing the tablets with a dusting phase may be of advantage, e.g. two portions
of a solution of acacia gum and sugar with talc, 14 mg/cm² in all, according to
G. Rothgang: APV-Informationsdienst 14 (4), 221 (1961).
Polymer requirement: P = 3 mg polymer per cm²
Tablet size: d = 7 mm, h = 3.6 mm
4. Equipment
Coating pan with warm air supply; possibly hairdryer, explosion-proof or at a safe
distance.
Accessories: hand sieve, graduated cylinder (50 ml), stainless-steel spatula and
ladle.
Polymer quantity: 70 g
Excipients (plasticizer): 14 g
Solids content: 9.9%
Coating weight: 3.5% polymer, corresponding to 3.1 mg/cm²(slightly
more than the quantity calculated above).
6. Preparation
Adjust the pan angle to approximately 75° and the speed to 25 to 35 rpm. Note these
conditions in the journal.
Prewarm the tablets to about 40 °C, pour on the film coating solution in 40 mL
portions in a thin stream and move the moist cores immediately with a spatula. If you
notice a tendency to sticking, dust the cores and the pan wall with approx. 15 mg
portions each of a mixture of talc and magnesium stearate.
Use a hand sieve for better distribution. Divide remaining agglomerations with a
spatula. When the cores rotate freely, blow in warm air for about 1 minute.
The total time required for one coating layer is about 5 minutes.
Perform this processing step always in exactly the same way, with more intensive
intermediate drying after five portions, so that any smell of solvent is eliminated. Take
samples of 10 to 20 tablets in each case.
Upon completion of the film coating process, rotate the pan ve ry slowly while
introducing warm air to heat the cores to 40 °C. Dry them at the same temperature
for another 2 hours in the oven and finally on trays at room temperature and normal
humidity overnight.
Journal entries:
Test the tablet samples taken with increasing coating thickness for disintegration in
simulated gastric and intestinal fluid according to exercise 1.2.3 and enter the results
in a diagram as shown on page 29 (Figure 6).
When the disintegration time in gastric fluid rises to over 2 hours, you know that
gastroresistance has been achieved and at which coating weight. You can also see
the extent to which the intestinal disintegration time is further increased with the
coating quantity.
The steeper the rise of the disintegration times in gastric fluid and the less
pronounced the increase in intestinal disintegration times, the better the quality of the
film coating.
The coating may be uneven, but there must not be any particles on top of it, no edge
chipping or cracking. At tablet bands the coating is usually somewhat thinner.
Exercise 1.2.1 can also be performed using a 6:4 ethanol/water mixture as the
solvent. The fire risk and load on the environment are then considerably reduced.
Moreover, this solvent mixture is easier to condense in offgas purification plants. In
this case, however, the drying times for the tablets at the beginning and end of the
coating process must be somewhat longer.
In production plants, the ladling process can be performed semi-automatically with
the aid of a peristaltic pump and distribution enhanced by means of a rake. Baffles
reduce the tendency to twinning. Talc and magnesium stearate as glidants can also
be suspended in the polymer solution.
1. Principle
Aqueous polymer dispersions are emulsion polymers which contain the film former as
submicroscopic latex particles.
Dispersions tend to coagulate under the influence of heat, frost or high shear, or
when electrolytes or finely divided solids (pigments) are added.
Therefore you are advised to adhere strictly to the formulation given.
Bear in mind the water sensitivity of the cores. At the beginning of the film coating
process dry as quickly as possible. Spray at a bed temperature which is about 10 to
20 °C higher than the minimum film-forming temperature. Use coating equipment
with the highest possible air-handling capacity.
The first few film coats close pores in the core and form a sealing coat that prevents
further water penetration.
2. Important Hints
Caution when handling flammable organic solvents for application of a sealing coat.
Prewarm tablets to 40 °C and apply the EUDRAGIT® sealing solution in one shot.
Prewarm the tablets also to about 40 °C before applying the film-coating dispersion
and after each such coating step.
Dusting is not required.
Post-drying at the end of the coating operation for at least 2 hours at 40 °C or 16
hours at room temperature and normal humidity.
Preparatory work:
Polymer requirement:
for sealing coat: Ps = 0.5 mg polymer per cm²
for enteric coating: Pe = 3 mg polymer per cm²
Coating weight in %
for sealing coat: 0.56% polymer = 11.2 g of polymer for 2 kg of tablets
Coating weight in %
for enteric coating: 3.30% polymer = 66.0 g of polymer for 2 kg of tablets
4. Equipment
Enteric coating
A latex-like dispersion has formed if virtually no particles are visible in a milky liquid
without any sediment formation.
The plasticizer is stirred in last.
The pH of the dispersion thus obtained should be 5.0 to 5.2.
7. Coating Procedure
Journal entries:
After applying 3 to 5 film coats, take 10 tablet samples and test their disintegration in
0.1 M HCl. Note the time for each tablet and enter the values in the diagram for
exercise 1.2.3 on page 29.
Test tablets which remained intact for more than 60 minutes subsequently in
simulated intestinal fluid pH 6.8. Enter the dissolution times of the gastroresistant
tablets in the same diagram.
For more accurate testing, see the individual monographs of the USP or Ph.Eur.
Given skillful operation, the tablets with a polymer weight of approx. 3 mg/cm² are
gastroresistant for at least 60 minutes and disintegrate within 30 minutes at pH 6.8.
Analyze the water content of the cores and enteric-coated tablets. It should increase
only slightly in the initial phase of the coating operation and revert to its original value
after drying.
If the water absorption is more pronounced, increase the thickness of the sealing
coat, reduce the individual shots and dry more intensively in between.
1. Principle
Good adhesion of the sugar coating to the polymer film must be ensured.
To this end you can dust the final film coat with acacia gum or incorporate the latter
in the first few sugar coats.
Addition of the aqueous polymer dispersion EUDRAGIT® L 30 D-55 to a conventional
sugar syrup containing acacia gum provides a good transition phase.
2. Important Hints
Since exclusively water-based formulations are used, there is no need to take any of
the precautionary measures associated with organic solvents because of their
flammability, toxicity and environmental hazard.
The sugar syrup should be mixed with the polymer dispersion while cold in order to
avoid coagulation.
Pigment suspension
6. Preparation
Stir the EUDRAGIT ® dispersion into the cold sugar syrup until a homogeneous, milky
liquid is obtained.
Suspend 11 g of acacia gum in 19 ml of water and stir to complete dissolution. Add
the yellow pigment to the cold syrup and homogenize in a ball mill or Ultra-Turrax.
Take care to entrap as little air as possible while homogenizing.
Stir the acacia gum solution into the air-bubble -free pigmented sugar syrup.
7. Coating Procedure
The pigmented sugar coat should come off in simulated gastric fluid within less than
15 minutes. The enteric coating beneath it must be undamaged and resist
disintegration in simulated gastric fluid for 2 hours. The disintegration times of the
cores in simulated intestinal fluid pH 6.8 are the same as in exercises 1.3.1 and
1.3.2.
If dusting with talc proves to be difficult on a production scale, stir the additive into the
dispersion syrup. In this case a quantity of 50 g per 100 g of syrup is sufficient.
1. Principle
Use a simple air gun for spraying that allows adjustment of the spray rate and the
droplet size.
Batch sizes of over 80 kg are required for continuous airless spraying.
Whenever possible, spraying should be done continuously.
The finely dispersed film former must dry quickly on the tablet surface.
There should be a minimum of twinning or sticking of tablets.
Tablets should not become too dry in order to avoid attrition and dust formation. Dust
and too rapid spraying may cause surface roughness.
Prewarm cores to about 25 °C.
A generous supply of drying air ensures rapid evaporation of the organic solvents.
During the spraying process the tablets should have a temperature of 20 to 25 °C.
2. Important Hints
The flammability and toxicity of organic solvents call for protection against explosion
and adequate ventilation.
Post-dry coated tablets carefully to remove residual solvents, i.e. for a minimum of 2
hours at 40 °C or 6 hours at room temperature (20 - 25 °C).
4. Equipment
6. Preparation
Stick 3 to 4 adhesive foam strips into the coating pan at right angles to the direction
of rotation.
Remove tablet dust with air.
Direct spray gun at the upper portion of the cascading cores. Adjust a fine spray with
compressed air at 0.5 bar. Test by first spraying against a sheet of blotting paper.
Adjust spray rate to about 20 mL per minute.
Control rate via the decreasing liquid level in the drip funnel.
Stir coating solution from time to time to prevent sedimentation of talc.
Introduce a gentle stream of warm air at 40 °C into the lower part of the pan while
spraying.
Keep the cores at about room temperature while spraying.
Interrupt the process when the cores are too moist or sticky. Dry until they once more
tumble freely. Spraying should not take longer than 60 to 80 minutes altogether. At
the very end, dry with warm air for 5 minutes at reduced pan speed. Spread tablets
on filter paper and air overnight.
Journal entries:
Suitable plasticizers besides triethyl citrate are polyethylene glycol, triacetin or dibutyl
sebacate in the same quantities.
EUDRAGIT® L 100 can also be replaced with EUDRAGIT® L 100-55 (soluble above
pH 5.5).
In the lower intestinal regions, coatings with EUDRAGIT® S start to dissolve gradually
above pH 7.
1. Principle
The usual polymer requirement for enteric coatings is 3 to 5 mg per cm², the weight
gain with pigments about 6 to 9%.
Polishing with an aqueous solution of polyethylene glycol provides high-gloss
coatings.
2. Important Hints
Prepare the pigment suspension according to exercise 2.2.1 the day before and
homogenize it overnight in a ball mill. Prepare a 12.5% polymer solution according to
exercise 1.2.1.
2.5 kg of tablets with methylene blue, provided with an enteric base coat of at least 2
mg of polymer/cm² according to exercise 1.3.4.
The polymer requirement for enteric coatings is 3 to 5 mg/cm².
Two thirds thereof, i.e. 2.0 to 3.3 mg of dry polymer substance per cm², should be
applied for the base coat according to exercise 1.3.1 and 1 to 1.7 mg of polymer per
cm² combined with pigments.
Tablet surface area 156 mm².
Pigmented film coat 1.1 mg/cm²:
(156 mm² · 1.1 mg/cm²) : 140 mg = 1.2% dry polymer substance
4. Equipment
Together with the enteric base coat from exercise 1.3.4, the total dry polymer
substance sprayed on is 5.1 mg/cm² = 5.6%
Quinoline yellow = FD&C Yellow No. 10
6. Preparation
Add triethyl citrate to the EUDRAGIT® solution, stir, and pour this mixture into the
pigment suspension with stirring.
7. Coating Procedure
Stick 3 or 4 adhesive foam strips into the coating pan at right angles to the direction
of rotation. Blow in air to dedust the tablets. Direct spray gun at the upper portion of
the cascading cores.
Adjust a fine spray at 0.5 bar and a spray rate of 20 mL per minute.
Stir polymer/pigment suspension in the funnel and reservoir at frequent intervals.
Introduce hot air at 40 to 50°C into the lower section of the pan.
Keep the core bed at approximately room temperature.
If the tablets become too moist or sticky, interrupt the spraying process briefly until
they are dry again.
The total spraying process should be completed within 60 to 80 minutes.
Post-dry with warm air for another 5 minutes.
Pour on solution of 1.0 g of polyethylene glycol 6000 in a mixture of 4.5 g of acetone
and 4.5 g of water and polish for 15 minutes without air supply.
Appearance: the coating should be smooth and glossy, also along bands and in
break lines.
The coated tablets are somewha t harder than the uncoated cores.
Testing for gastroresistance: the tablets should resist gastric fluid for a minimum of 2
hours and disintegrate in intestinal fluid pH 6.8 within 30 minutes as described in
exercise 1.2.3.
Gastroresistance must also be given under mechanical stress, e.g. in the friabilator
(100 rev./4 min).
9. Possible Modifications
1. Principle
Aqueous polymer dispersions contain the film former as minute latex particles of less
than ∅ 1 µm.
These particles coalesce to a water-insoluble film.
Aqueous dispersions are environment-friendly and avoid the risks associated with
organic solvents, i.e. flammability and toxicity.
Their minimum film-forming temperature (MFT) has to be observed, however.
Aqueous dispersions are easily atomized by means of pneumatic nozzles.
For details see exercise 2.1.2 "Technical Aspects of the Manufacture of Rapidly
Disintegrating Coatings."
Dispersions are sensitive to electrolytes, frost, heat, changes in pH, organic solvents
and high shear, and they tend to foam formation.
Coagulated dispersions cannot be redispersed and must be discarded.
2. Important Hints
Ensure rapid evaporation of the water by introducing a copious amount of drying air.
Spraying should be performed continuously with simultaneous drying.
Preheat the cores to about 40 °C. Maintain the core bed at a temperature around
30 °C.
Use talc as a glidant, polyethylene glycol 6000 as a plasticizer and silicone emulsion
as an antifoam agent.
Dry coated cores carefully before further processing.
For 2.5 kg of cores, this adds up to 111 g of dry polymer substance contained in 111
g · 100 : 30 = 370 g EUDRAGIT® L 30 D-55.
4. Equipment
6. Preparation
Start by finely homogenizing talc, polyethylene glycol 6000 (as a 10% aqueous
solution), antifoam emulsion and water (Ultra-Turrax, 5 to 15 minutes) and stir this
mixture rapidly into the available dispersion.
Adhere strictly to the order and procedure of adding the excipients.
7. Coating Procedure
Stick 3 to 4 adhesive foam strips into the coating pan at right angles to the direction
of rotation. Prewarm the tablets at reduced pan speed (approx. 20 rpm) to 40 °C.
Appearance: The coating should be smooth and glossy and cover the tablets evenly,
also along bands and edges.
Testing for gastroresistance: in the disintegration tester to DAB/USP, samples of the
film-coated tablets should resist gastric fluid for a minimum of 2 hours and then
disintegrate in intestinal fluid pH 6.8 within 20 to 40 minutes.
The dissolution of the actives can be measured additionally.
To determine the optimum polymer quantity, take an adequate amount of samples
and test these according to exercise 1.2.3.
9. Possible Modifications
1. Principle
Pre-formulated, ready-to-use pigment suspensions or dry ble nds are also available.
Manufacturers of these products also offer color-matching service. By color matching,
optimal pigment combinations can be established during development of a product.
2. Important Hints
3. Equipment
4. Product
10 kg of placebo tablets, diameter 7 mm, height 3.6 mm, weight 140 mg.
Disintegration in water and simulated gastric fluid max. 5 min.
5. Polymer Requirement
72
S = π ⋅ 7 ⋅ 3.6 + = 156. mm²
2
156 ⋅ 5
= 56%
. polymer , for 10 kg tablets, these are approx. 560 g.
140
6. Formulation for 10 kg of Tablets
Polymer/pigment suspension
2
1N NaOH 188 g 0.2%
Talc 279 g 7.0%
Triethyl citrate 56 g 1.4%
2
Polyethylene glycol 6000, 33% aqu. 66 g 0.6%
Titanium dioxide 56 g 1.4%
FD&C Yellow No.10* 17 g 0.4%
Water 1459 g 75.0%
3978 g 100.0%
* color lake based on quinoline yellow, E 172
1
dry polymer substance
2,
solid substance
To prepare the final film coating suspension, the ingredients must be poured together
in this order:
Feed 1N NaOH slowly into EUDRAGIT L 30 D-55 with gentle stirring for 5 minutes.
Suspend the other excipients in the remaining water and homogenize for 20 minutes
using a colloid mill. Then add the pigment suspension to the stabilized EUDRAGIT L
30 D-55 with slight stirring for 5 min.
7. Working Instructions
The coating should be smooth and shiny and provide uniform cover even over edges.
Hardness is about 70 N.
Gastric resistance is given for 2 hours, followed by a disintegration in simulated
intestinal fluid BP 80, pH 6.8, within 5 minutes.
9. Possible Modifications
1. Principle
The Hüttlin Kugelcoater is a typical apparatus for bottom spray technique. It can be
used for coating tablets, pellets, granules, crystals and powders.
The spherical product container is fitted with spray guns beneath the product bed,
which allow concurrent spray application of the polymer suspension. The specially
designed spray guns produce a "microclimate" around the spray which avoids spray-
drying effects.
Owing to the high drying -air capacity, rapid and effective drying is possible, and thus
shorter processing times. All standard formulations with EUDRAGIT polymers can
be used in this equipment without any change in composition.
2. Important Hints
During prewarming, the particles should be fluidized carefully with reduced air flow in
order to minimize mechanical stress on the particles. When the first few coating
layers have been applied, the particle surfaces are stabilized to a certain extent.
Towards the end of the coating process, intensive fluidization should be prevented so
as to avoid damage to the coating.
Compared to top spray processes with coating suspensions, bottom spray technique
provides a more uniform, homogeneous coating with fewer defects. In many cases,
the amount of polymer required for the same coating function can be reduced.
3. Equipment
4. Product
5. Polymer Requirement
The surface area of the ASA crystals can be estimated according to exercise 3.2.2
and then calculated as in exercise 1.1.2. If dimensions are not available, perform a
small-scale test and take 5 to 10 samples between 5 and 25% polymer weight gain.
Make a drug release test, which will show the optimum amount of polymer.
6. Formulation for 4.0 kg of Crystals
Spray suspension:
* ferric oxide
7. Coating Procedure
Fill the crystals into the Kugelcoater HKC 5 and preheat to approx. 25-30°C. Adjust
the drying air to 150m³/h and 40°C, the atomizing air pressure to 1.5 bar and the
pressure for the microclimate to 1.6 bar.
After about 3 min, start the peristaltic pump (8 rpm = ~ 26g/min.). During the coating
process the product temperature should be kept between 25 and 30°C by adjusting
drying-air volume and temperature.
Maintain a steady flow of crystals while coating. If any signs of sticking are noted,
interrupt spraying until the pellets are sufficiently dry to allow unimpeded fluidization.
Then continue spraying at a reduced rate.
The whole process takes approx.150 min. The coated crystals are then dried for 2
min. at reduced air flow and are finally discharged from the coating equipment and
spread out on trays for a final drying at 40°C within 2 hours.
Measure the drug release according to USP 23, apparatus 2, 50 rpm. 250 mg ASA/
800 ml 0.1N HCl. Buffering for 2 hours with 22g Na 3PO4 x 12 H2 O in 100 ml 0.1N
HCl.
Time [h] 1 2 | 3
Drug dissolved [%] 3 5 | 96
1. Principle
Spray coating of small batches from 1 to 20 kg serves above all for designing useful
formulations and defining the limits of polymer consumption.
When larger equipment is used, the polymer quantity can often be reduced, because
less spray is lost and the film former is more evenly distributed.
In large coaters it is often easier to position the nozzle within the fluidized bed. The
spray that is carried upwards with the drying -air can then still settle on the product.
When validating the process, make sure to observe the official regulations and
recommendations.
When designing the formulations, allow adequate scope for variation of all excipient
quantities, so that you can reproduce the desired release profiles despite changes in
raw material quality and process parameters.
Even on a production scale you should take samples of coated product to check the
specified polymer quantities. This is a simple way to prove your growing experience
and the increasing effectiveness of your coating process and allows you to see what
scope you have in achieving products that meet the standards.
2. Important Hints
When working with organic solvents, make sure that your equipment and the vessels
are explosion-proof and adequately grounded. For the present exercise purely water-
based EUDRAGIT® L 30 D-55 is used.
If a polymer dispersion contains suspended pigments or other solids which need to
be evenly distributed, the storage vessel must be stirred throughout the coating
process to avoid sedimentation. For the same reason, the feed tubes to the spray
guns should be as short as possible.
150 kg of acetylsalicylic acid crystals, particle size 0.315 - 1.25 mm (supplier: Aubing,
Munich)
The surface area of the ASA particles can be measured according to exercise 3.2.2.
Given a weight-specific surface area of 100 cm²/g and a polymer application of 3
mg/cm² for enteric coating, the resultant dry polymer weight is 300 mg per g of ASA
or 30% of active. In practice, however, 10 to 20% polymer is usually sufficient, i.e.
approx. 1 to 2 mg/cm².
Where data for calculation of the total surface area are not available, the polymer
requirement must be determined in laboratory trials. When doing so, bear in mind
that the coating procedure on a production scale is usually more effective than the
laboratory process, so that the polymer quantities can be reduced during scale-up.
Sampling and intermediate testing for drug release is always advisable, as it permits
you to apply your findings immediately to the next batch.
4. Equipment
Fluid bed coaters WSG 30/WSG 60 with exhaust air screen (Glatt, Binzen),
peristaltic pump with silicone tube, internal diameter 8 mm;
storage vessel with pneumatic stirrer.
6. Working Instructions
Set the exhaust air flap for slight fluidization of the active crystals and prewarm to
approx. 30 °C.
The nozzle aperture should be 1.8 to 2.2 mm. A spray rate of 5 to 6 g of dry polymer
substance/min/kg of crystals will be adequate in the majority of cases.
During spraying, the temperature of the outlet air decreases to approx. 25 °C. The
temperature in the product bed should not exceed 30 °C.
If agglomeration occurs, interrupt the spraying process until the crystals are dry and
once more able to float freely. If necessary, introduce more air. Then continue
spraying at a reduced rate and/or increased air supply.
The entire process takes about 2 hours. Upon its conclusion, dry for 5 to 10 minutes
at reduced fluidization, then spread the coated crystals on trays for airing. Drying in
an airflow oven within 6 hours at 40 °C is more effective.
Testing for drug release can be performed according to exercise 3.3.6 and in
observation of the principles described in exercise 3.2.3.
Drug release in gastric fluid should be as low as possible, but quantities below 5%
per hour are still acceptable. Given skillful operation, less than 1% release can be
achieved [17].
Owing to the acidic reaction of the embedded acetylsalicylic acid, the dissolution of
the film coating slows down in buffer solutions of pH 6 to 7.5, so that the larger part of
the active is initially set free by diffusion. The coating only dissolves towards the end
of the release test.
Since the polymer substance is insoluble below pH 6, you must check that the pH
has not dropped below this value because of liberated ASA and is actually within the
specified range.
8. Possible Modifications
The dispersion thus obtained can be handled and processed just like EUDRAGIT® L
30 D-55 (see exercise 1.2.2).
For the manufacture of a so-called slow-release preparation with the same ASA
crystals, i.e. a dosage form for gradual drug release from the stomach onwards,
polymer quantities of only 1.5 to 2.5% are sufficient, with no other changes in the
formulation.
Table 7 Technical Data of Various Types of Equipment
1. Principle
2. Important Hints
Polymer dispersions may coagulate when exposed to high shear and mixing
operations. Please observe the working instructions.
Take care to prepare the pigment suspension separately one day before the polymer
dispersion.
Pigments on their own can be homogenized in high-speed dispersion equipment
(e.g. Ultra-Turrax, corundum disk mill, toothed colloid mill).
Avoid foam formation as a result of too much air entrapment.
Add some antifoam agent and wait for the air to escape.
Mix pigment suspension and EUDRAGIT® dispersion only just before use and take
care not to generate high shear.
Preparatory work:
Prepare pigment suspension the day before according to exercise 2.2.1 on page 89
(No. 6).
3. Product / Polymer Requirement
2.5 kg of tablets provided with an enteric base coat of 4 mg of dry polymer substance
per cm² according to exercise 1.3.6.
The polymer quantity for the top coat depends on the amount of pigment required for
uniform coloring, which should be about 1 mg/cm², plus the same or twice the
amount of talc. The polymer quantity needed for binding the pigments is 0.8 mg/cm².
Polymer/pigment suspension
EUDRAGIT® L 30 D-55
(30% dispersion) 75 g 5.0%1
Pigment suspension* (30%) 250 g 16.7%2
Water 125 g 78.3%
450 g 100.0%
6. Preparation
Have the finely homogenized pigment suspension ready (prepared in a ball mill the
day before according to exercise 2.2.1, no. 6). Dilute it now with the water quantity
stated and stir the mixture quickly into the EUDRAGIT ® dispersion, using the spatula.
7. Coating Procedure
Stick 3 to 4 adhesive foam strips into the coating pan at right angles to the direction
of rotation. Prewarm the tablets to approx. 40 °C.
Maintain the core bed at about 30 °C throughout the coating operation.
Direct the spray gun at the upper third of the cascading cores while continuously
introducing warm air (50 to 80 °C).
Adjust the atomizing air pressure to between 0.5 and 1 bar so as to obtain a very fine
spray.
Deliver the spray suspension from a drip funnel or by means of a peristaltic pump
and feed at a rate of 6 to 8 mL per minute.
If the cores become too wet, interrupt the spraying process and dry for a few
minutes. The entire coating operation should be completed within 60 to 80 minutes.
Post-dry the film-coated tablets in the coating pan for another 5 minutes.
The coating should be dry and glossy and of uniform color, also along tablet bands
and edges.
Test the tablets for gastroresistance according to exercise 1.2.3. Even after treatment
in the friabilator (100 rev./4 min), they should withstand gastric fluid for a minimum of
2 hours.
9. Possible Modifications
For the sake of convenience you may use a commercially available pigment
suspension. Manufacturers offer to develop the any desired shade with only slight
variations from batch to batch.
The compatibility of such ready-to-use preparations must be tested from case to
case. Concentrates and dry mixtures need to be diluted to 30% solids to be suitable
for use with the formulation stated under 5.
If this formulation is processed as a colored protective coating on ordinary tablets,
the delayed disintegration in gastric fluid also depends on the swelling and
disintegration behavior of the cores themselves. Owing to its low permeability, the
sealing effect of EUDRAGIT® L film is superior to that the of the rapidly disintegrating
coatings according to exercises 2.3.1 to 2.3.4.
1. Principle
The anionic polymer EUDRAGIT® S 100 contains 30% methacrylic acid units and
forms enteric films which only start to dissolve above pH 7.
The powder obtained by spray drying of the emulsion polymer can be redispersed to
a latex via partial neutralization up to about pH 6.
The addition of 50% triethyl citrate as a plasticizer is required to lower the film-
forming temperature to the processing range of 25 to 35 °C and thus to obtain less
brittle and crack-free films.
The use of talc as a glidant and of pigments for coloring is optional.
2. Important Hints
The coating formulation in the storage vessel should be permanently stirred to avoid
sedimentation of talc or pigments.
Preparatory work:
Disperse EUDRAGIT® S 100 powder according to exercise 1.2.2 one day before
starting the coating operation. The base to be employed in this case is ammonia
solution (see under '6. Preparation'). Prepare the pigment suspen-sion also the day
before.
4. Equipment
Figure 9
Pigment suspension
Talc 219.6 g
Titanium dioxide 58.0 g
FD&C Yellow No. 10 88.0 g
Antifoam emulsion 2.0 g
Water 754.4 g
1120.0 g = 365.6 g solid substance
6. Preparation
Prepare the EUDRAGIT® S 100 dispersion according to exercise 1.2.2 one day in
advance. After adding the ammonia solution, continue stirring for another 60 minutes,
and the same after adding triethyl citrate. Finally pass the mixture through a 0.25 mm
sieve.
Prepare the pigment suspension separately. Start with water and talc, pour on
titanium dioxide and yellow pigment and stir gently with the spatula. Add antifoam
emulsion and disperse in an Ultra-Turrax, colloid mill or similar apparatus within 10
minutes. Leave the suspension to stand for at least one hour, but preferably
overnight, so that entrapped air can escape.
Prepare the polymer/pigment solution by pouring the pigment suspension into the
diluted EUDRAGIT® S dispersion and stirring gently by hand with the spatula or using
a broad-paddle mixer at low speed (approx. 30 rpm).
7. Coating Procedure
Set the idle equipment to the parameters stated below. After testing its functions, fill
in the tablets and prewarm to 40 °C at 50% pan speed while extracting dust. Then
spray for 5 to 10 minutes at full rotational speed until all tablets are slightly moist and
superficially sealed.
Adjust the spray rate to the air-handling capacity, so that the cores are always moist
but never wet. In the latter case, interrupt the spraying process for intermediate
drying. After applying about two thirds of the specified coating weight, take samples
for testing the enteric properties.
Rotational speed 11 rpm
Atomizing air pressure 1.3 bar
Flat spray pressure 0.6 bar
Relative humidity 32%
Inlet air temperature 45 - 50 °C
Outlet air temperature 32 °C
Inlet/outlet air capacity 11.3/>12 m³/min
Bed temperature 30 °C
Spray rate 46 g/min (4.6 g/min per kg)
Total spraying time 147 min
Qty. of suspension applied 6700 g = 1350 g solid substance
Final drying in pan 3 min. at 42 °C and 5 rpm
Post-drying on trays 2 hrs in airflow oven at 40°C, 24 h at RT
(50 - 60% RH)
The coating should be smooth and glossy. There must be no erosion along bands or
edges, with adequate coating thickness in these areas. Microscopic evaluation:
nowhere must the coating thickness be less than 10 µm.
Conduct the test for gastroresistance, also on samples previously taken to examine
the abrasion along edges.
The coated tablets should withstand simulated gastric fluid for 2 hours and buffer
solution pH 6.4 for at least 1 hour. Dissolution of the coating and disintegration of the
tablet in intestinal fluid pH 7.4 within maximally
30 minutes.
9. Possible Modifications
If pigments are unwelcome, do use the stated quantity of talc, however, in order to
prevent sticking and to achieve a smooth coating.
1. Principle
2. Important Hints
Preparatory work:
1 kg of hard gelatin capsules, size 00, 'snap-fit' (Capsugel, Basel, Switzerland), filled
with lactose; weight 986 mg, ∅ 8.5 mm, total length 23.5 mm.
Polymer quantity 17 mg/cm². (This is roughly three times the quantity for tablet
coatings!)
S=π ⋅d⋅l
S= 3.14 ⋅ 8.5 mm ⋅ 23.5 mm = 627.2 mm²
4. Equipment
Solids content 5.0%, coating weight 3 to 5 mg solids per cm² of surface area,
corresponding to between 17.5 and 29.0 g per kg of capsules.
6. Preparation
Start by stirring talc and triethyl citrate into the water quantity stated (414 g) and
homogenize the mixture in an Ultra-Turrax for 5 minutes. Then add two drops of
silicone antifoam emulsion, allow 30 minutes for entrapped air to escape and stir this
suspension into the 30% EUDRAGIT® L 30 D-55 dispersion using the spatula.
7. Coating Procedure
9. Possible Modifications
Soft gelatin capsules can be coated in the same way. In this case, however, residual
oil may have to be removed.
Our technical advice on the uses of our materials is given without obligation. The buyer is responsible for the application and
processing of our products and is also liable for observing any third-party rights. Technical data concerning our products are
typical values. ® = registered trademark. EUDRAGIT = reg. Trademark of Röhm GmbH, Darmstadt