Introduction:
Generally pharmaceutical drug products exist in two dosage forms, solid and liquid dosage
forms. Included in solid dosage forms are tablets, pellets, pills, beads, spherules, etc. These solid
dosage forms are frequently coated for various reasons, such as odor or taste masking, prevention
from moisture, light and/or air, protection from destruction by gastric acid or gastric enzymes,
enhanced mechanical strength, aesthetics or controlled release including controlling release sites
and/or release rate. The major technique employed in the pharmaceutical field for the
manufacturing of coated solid dosage forms are based on the deposition of different materials
onto substrate cores from solutions or suspensions. Therefore, the evaporation of large amounts
of liquids (no less than 70% w/w with respect to coating material) is required. During the last
two decades, pharmaceutical coating technology has been shifting from organic solvent-based
systems to aqueous systems, which are advantageous1–3.
However, aqueous coating systems are not always applicable, for example if the active
ingredient is sensitive to water. From the view point of cost, usage of water in place of organic
solvent is highly beneficial. However, reduction of processing time and coating level are also
important. A simple way to shorten coating time is to use a coating solution or dispersion of
higher concentration, but this approach is limited by the viscosity increase of the solution or
blocking of the spray nozzle4. In order to overcome these limitations of the liquid coating
technology, new efforts have been made in recent years to develop solventless coating
technologies. The developed solvent less coating technologies include hot-melt coating,
supercritical fluid spray coating, photo curing coating and powder coating. The dry particle
coating is defined as technology to coat the particles without using organic solvent or water
dispersion5.
Advantages 6
1. Powder coatings emit zero or near zero volatile organic compounds (VOC).
2. Powder coatings can produce much thicker coatings than conventional liquid coatings
without running or sagging.
3. Powder coating overspray can be recycled and thus it is possible to achieve nearly 100%
use of the coating.
4. Powder coating production lines produce less hazardous waste than conventional liquid
coatings.
5. Capital equipment and operating costs for a powder line are generally less than for
conventional liquid lines.
6. Powder coated items generally have fewer appearance differences between horizontally
coated surfaces and vertically coated surfaces than liquid coated items.
7. A wide range of specialty effects is easily accomplished which would be impossible to
achieve with other coating processes.
Disadvantages
While it is relatively easy to apply thick coatings which have smooth, texture-free surfaces, it is
not as easy to apply smooth thin films. As the film thickness is reduced, the film becomes more
and more orange peeled in texture due to the particle size and glass transition temperature (TG)
of the powder. Also powder coatings will break down when exposed to UV rays between 5 to 10
years. On smaller jobs, the cost of powder coating will be higher than spray painting.
For optimum material handling and ease of application, most powder coatings have a particle
size in the range of 30 to 50 μm and a TG above 40°C.For such powder coatings, film build-ups
of greater than 50 μm may be required to obtain an acceptably smooth film. The surface texture
which is considered desirable or acceptable depends on the end product. Many manufacturers
actually prefer to have a certain degree of orange peel since it helps to hide metal defects that
have occurred during manufacture, and the resulting coating is less prone to showing
fingerprints.
There are very specialized operations where powder coatings of less than 30 micrometres or with
a TG below 40°C are used in order to produce smooth thin films. One variation of the dry
powder coating process, the "Powder Slurry" process, combines the advantages of powder
coatings and liquid coatings by dispersing very fine powders of 1–5 micrometre particle size into
water, which then allows very smooth, low film thickness coatings to be produced
METHODS AND PRINCIPLE OF DRY COATING
Powder coating technology are termed as dry coating technologies, in which powdered coating
materials are directly coated on to solid dosage forms with no using any solvent, and then
heated and cured to form a coat. Solid dosage forms are dissimilar in numerous aspects from
those metal substrates. Solid dosage forms are with weak electrical conductivity whereas metal
substrates are very electrically conductive. Moreover, film-forming polymers for solid dosage
forms are completely thermoplastic other than thermosetting which is a common case for metal
substrates. For thermoplastic film-forming polymers, plasticizers are often added to lower the
softening temperature (Ts) or glass transition temperature (Tg) of the polymers, allowing film
formation at a reduced temperature and improving the flexibility and tensile strength of the
obtained coat. The majority of plasticizers are liquid organic chemicals with small molecular
weight and low volatility. Generally, Ts or Tg reduces with the increase of plasticizer polymer
ratio. When plasticizer polymer ratio is increased to an extent that the reduced Ts or Tg is close
to or below the room temperature, the polymer film will become soft and sticky, having no
practical values.
Plasticizer-dry-coating
The first dry coating technology is mainly based on the usage of plasticizers. Here, this
technology is referred to as “plasticizer-dry coating”. For solid dosage coating, low Ts or Tg of
the film-forming polymer is essential to protect active pharmaceutical ingredients (APIs) in the
dosages from being damaged at a high temperature. This necessitates the use of plasticizers. For
example, cellulose derivatives such as hydroxypropyl methylcellulose acetate succinate
(HPMCAS), a commercial cellulosic enteric coating polymer, and ethylcellulose, an extended
release agent, depend on plasticizers of acetylated monoglyceride (AMG), acetyltributyl citrate
(ATBC) or triethyl citrate (TEC) to bring their Tg or film-forming temperature from more than
100 ◦C down to 60◦C or less4. In plasticizer-dry-coating technology, powdered materials are
sprayed onto dosage surface simultaneously with the plasticizer spraying from separate spraying
nozzle. The sprayed liquid plasticizer would wet the powder particles and the dosage surface,
promoting the adhesion of particles to dosage surfaces. The coated dosages are then cured for a
predetermined time above the Tg of the polymer, forming a continuous film. The adhesion of
particles to dosage surface is mainly the result of the said wetting of particles and dosage
surfaces by plasticizers, and the film formation is the combined response of improved viscous
flow and particle deformation resulted from plasticizer and heat. In addition, capillary forces
exerted by liquid plasticizer prior to its uptake into the polymer particles may also contribute to
the particle deformation in the interstitial capillary system between particles and thus to the film
formation7-8. Obara et al. reported that, in their plasticizer-dry coating process, spraying a small
amount of water or hydroxypropyl methylcellulose (HPMC) solution to their HPMCAS-coated
spheres could obviously improve the film quality; it is also been suggested that moisture would
significantly accelerate the film formation and optimize the film smoothness and integrity of
ethylcellulose-coated pellets during the heat curing phase9. These phenomena are similar to those
observations for film formation of aqueous dispersions. For these cases, water or water in the
polymer solution plays a role of coalescing solvent or plasticizer promoting the inter diffusion of
polymer chain, and the evaporation of water may also provide a driving force to fuse the
polymeric particles based on the film formation mechanism proposed for aqueous latex
systems10, 11.
Electrostatic-dry-coating
Another dry coating technology is based on the electrostatic powder coating technology, here
called “electrostatic-dry-coating”. Electrostatic coating of solid dosages with powdered materials
is more difficult than coating of metals due to the much weaker electrical conductivity of solid
dosages than metal substrates. For metal substrates, the sufficiently strong electrostatic attraction
between the charged particles and the grounded metal substrate makes particles to firmly adhere
to the substrate surface, producing a coat with a desirable thickness. For solid dosage forms,
however, the electrostatic attraction between the charged particles and the solid dosages with
weak conductivity or high electric resistance is typically weak, leading to difficulty in producing
a thick coat. Despite this difficulty, the benefits of electrostatic-dry-coating including more
uniform coat and more accurate control of coat thickness in comparison with the “plasticizerdry-coating” have been encouraging researchers to devote efforts to surmount this difficulty of
the electrostatic-dry-coating. Phoqus Pharmaceuticals Limited, an oral drug delivery and
development company located in Kent, the United Kingdom, has been devoting great efforts in
designing both apparatus and formulations of powdered coating materials in order to fulfill
electrostatic coating of solid dosage forms, and many patents in this field have been produced.
Phoqus has applied electrostatic-dry-coating technology for the preparation of its lead product
Chronocort, a once-daily modified release hydrocortisone tablet for the treatment of adrenal
insufficiency, and successfully completed the phase I clinical trials in 2006
12
. The shinning
features of the electrostaticdry- coating technology include uniform coating surfaces with
controllable thickness and, if needed, with different color or formulation. So far, the published
electrostatic-dry-coating technologies mainly focused on coating tablets. Endeavors are being
made aiming to coat smaller solid dosage forms such as pellets or beads by means of the
electrostatic-dry-coating.
Heat-dry-coating
The third dry coating technique was developed by Cerea et al. This technique is also called as
“heat-dry-coating” since only heat was used as a “binding force” to realize the dry coating of
tablets. In this coating technology, Eudragit E PO (a copolymer based on dimethylaminoethyl
methacrylate and methacrylates) particles were continuously spread onto the tablets contained in
a lab-scale spheronizer by way of a motorized single screw powder feeder, with an infrared lamp
positioned on the top of the spheronizer as a heating source, without using any solvent and
plasticizer. Powder adhesion onto the tablet surface is promoted only by the partially melted
polymer that generates binding forces between particles, and between particles and tablet
surfaces13.
RESEARCH AND APPLICATION OF DRY COATING
Flow improvement:
Some study indicates that it is possible to change the properties of silica gel particles by coating
with hydrophobic magnesium stearate using both the Hybridizer and Cyclomix as dry coating
devices. The ESEM images of the uncoated and coated particles in the two devices show that
magnesium stearate was softened and smeared over host particles. But the silica gel treated alone
in the Cyclomix was crushed whereas no difference was observed after processing in the
Hybridizer. The coating of silica gel particles seems to be more uniform and the magnesium
stearate is much more softened and smeared over the surface of silica gel particles processed in
the Hybridizer than the surface coverage obtained after treatment in the Turbula mixer. The
flowability of the silica gel powder was not strongly affected by coating in the Hybridizer and
remains good. The flow properties of silica gel are more significantly decreased after treatment in
the Turbula mixer than in the Cyclomix mixer. This is probably due to the quality difference in
the particle coating. It is also found that the coating by hydrophobic magnesium stearate in both
the Hybridizer and Cyclomix can also reduce the high affinity between silica gel and water 14.
The treatment of silica gel powder with 5% and 15 % of magnesium stearate in the Turbula
mixer also reduce its affinity with water. To summarize, it has been demonstrated that a dry
particle coating technique can be used to modify the properties of silica gel powder by coating
with small quantities of hydrophobic magnesium stearate in both the Hybridizer and the
Cyclomix. The more uniform coating is obtained after treatment in the Hybridizer device.
Some study of the ageing of the coated silica gel powder has demonstrated the influence of
storage conditions, in particular, the relative humidity on the stability of the coated surfaces.
Indeed, for relative humidities varying between 30 % and 50 %, the surface coverage by
magnesium stearate disappears after only 36 days storage. The surface of silica gel particles finds
its initial hydrophilic characteristic. Under these conditions of relative humidity, the silica gel
powder absorbs water vapor and silanol groups (Si–OH) are formed onto the surface
15
. On the
other hand, the storage under drier air (relative humidity below t o 12%) preserves the coated
surfaces. Some thermo gravimetric analysis evidence that the magnesium stearate material is still
in the silica gel particles. To explain the disappearance of magnesium stearate from the surface
of silica gel, the mechanism of diffusion of magnesium stearate from the surface into the pores of
silica gel particles may be considered. This ageing mechanism is enhanced by high relative
humidity. Finely, it is important to confirm by other analysis techniques the validity of this
hypothesis of diffusion and what are the major mechanisms to explain the rapid ageing of the
coated silica gel powder under humid atmospheres.
Dry enteric coating
S Obara et al examined dry coating for tablets using a commercially available coating machine.
In order to deliver the powder uniformly onto the tablets in the pan, compressed air was used to
force the powder out of the tube, like a liquid spray under a controlled condition. The outlet
temperature was controlled at approximately 420 C during the coating process, as in the other
experiments. During the process, no blocking was observed in the powder feed line. Before the
curing process, the coated surface was rough, and film formation was not observed, but after it,
the surface layer formed a continuous film. Surprisingly, the film formed within a very short
time, approximately 10 min, after the addition of a small amount of water (3% of dry core). They
also have studied that the required coating level for sufficient gastric resistance was 8% with
respect to the core weight. Uptake of the gastric fluid was 2.1%, which was almost the same
level as that of tablets with aqueous coating. The disintegration time at pH 6.8 was 10 min, again
similar to that of tablets with the conventional coating. The appearance of the tablet surface is
important for pharmaceutical products, and the surface of the tablets obtained by dry coating was
slightly rougher than that of the samples with conventional coating, but was regarded as being in
the acceptable range. The surface appearance depended on the oily additive used, and was
smoothest when acetylated monoglyceride was used. In this study, the core tablets were coated
with HPMC prior to dry coating. Without the sub-coating, the gastric resistance after dry coating
was not satisfactory. This may be because the sub-coating layer prevents from the penetration of
plasticizer into the core, or because the uncoated surface was damaged and became rougher
during the curing process. The beads did not require sub-coating4.
Dry powder coating to provide extended drug release
N Pearnchob et al deliberate that Micronized ethyl cellulose powder can be coated on pellets by a
dry powder coating technique to provide extended drug release. The process has many
advantages when compared to classical coating techniques (e.g. coating with organic polymer
solutions or aqueous dispersions), such as shorter processing times. A novel coating technique
with ethyl cellulose based on the coating with micronized ethyl cellulose powder was
investigated in order to achieve extended drug release. Ethyl cellulose has a high glass transition
temperature of approximately 130oC. A plasticizer therefore had to be sprayed in parallel to the
feeding of the polymer powder into the coating chamber in order for the micronized polymer
particles to coalesce into a film. The plasticizer was added to an aqueous HPMC solution, which
also assisted in the adhesion of the polymer particles to the surface of the pellets prior to film
formation16.
Immediate release coatings
Qiao M at al. studied novel electrostatic dry powder coating technique based on liquid pan coater
was developed and applied form immediate release coatings with Opadry, AMB and Eudragit
EPO. Liquid plasticizer was used to decrease Tg of coating polymers and to promote powder
deposition on the tablet surface by increasing electrical conductivity of tablets. Even though the
enhanced electrical conductivity of tablets met the requirements for electrostatic coating, it is still
necessary to further improve the electrical conductivity in order to make full use of electrical
attractive force. The dry coating particles fused into a complete film on the tablet surface after
curing at elevated temperatures. The electrostatic powder coating technique is able to produce
smooth and uniform coating film and has been demonstrated as a promising alternative to
traditional aqueous-based coating process. However, the electrostatic dry powder coating process
is still new and requires further validation through more experiments17.
Humidity resistance dry particle coating
Dry particle coating is used to enhance the moisture resistance of ground magnesium powder
(primary size 75 Am) by coating its surface with carnuba wax (primary size 15 Am). Coating
was done using magnetically assisted impact coating (MAIC), and two high-speed impactioncoating devices, the hybridizer and mechanofusion. In this study, a cost-effective,
environmentally benign method has been developed which improves the moisture resistance of
ground magnesium and hence its shelf life by delaying the formation of magnesium hydroxide.
This was accomplished using various dry particle-coating devices to coat ground magnesium
powder with carnuba wax or fumed silica. The wax-coated magnesium samples were tested
(fired) at Picatinny Arsenal and the coating showed no adverse effect on their pyrotechnic
properties, other than a slight loss of bulk density that directly relates to the loss of energy
density 18.
Dry powder-coating technique Enhanced oral bioavailability
In this study, novel mucoadhesive polymer-coated pellets with enhanced bioavailability were
successfully designed for VAL by using a dry powder-coating technique. The core pellets
containing poloxamer 188 as a solubilizer and NaOH as a pH modulator showed significantly
higher drug release rate than common pellets or drug powder in vitro. The coating of
mucoadhesive polymers, i.e. HPMC and CB, did not alter the drug release pattern from the
coated pellets, which showed almost identical release profiles as the core pellets. Strong
molecular interactions between the drug and the carriers were demonstrated by FI-IR analysis.
The powder-coated pellets coated with a mixture of HPMC and CB (1:2) showed desirable
swelling performance and mucoadhesive property in vitro, as well as extended GI transit in vivo.
In addition, this dry powder-coated pellets gave the significantly higher AUC and Cmax
compared to the core pellets (1.9 and 1.7 fold) or drug suspension (3.5 and 1.8 fold) in rats19.
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