Recent Advancement in Drug Technology1 Chabges

RECENT ADVANCEMENT IN DRUG TECHNOLOGY
INTRODUCTION
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances

and excipients, usually in powder form, pressed or compacted from a powder into a solid
dose. The excipients can include diluents, binders or granulating agents, glidants (flow
aids) and lubricants to ensure efficient tabletting disintegrants to promote tablet break-up
in the digestive tract sweeteners or flavours to enhance taste; and pigments to make the
tablets visually attractive. A polymer coating is often applied to make the tablet smoother
and easier to swallow, to control the release rate of the active ingredient, to make it more
resistant to the environment (extending its shelf life), or to enhance the tablet's
appearance.
The compressed tablet is the most popular dosage form in use today. About two-thirds of
all prescriptions are dispensed as solid dosage forms, and half of these are compressed
tablets. A tablet can be formulated to deliver an accurate dosage to a specific site; it is
usually taken orally, but can be administered sublingually, buccally, rectally or
intravaginally. The tablet is just one of the many forms that an oral drug can take such as
syrups, elixirs, suspensions and emulsions. Medicinal tablets were originally made in the
shape of a disk of whatever color their components determined, but are now made in
many shapes and colors to help distinguish different medicines. Tablets are often stamped
with symbols, letters and numbers, which enable them to be identified. Sizes of tablets to
be swallowed range from a few millimeters to about a centimeter.
Tabletting Formulations
In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered
or granular, somewhat uniform in particle size and freely flowing. Mixed particle sized
powders segregate during manufacturing operations due to different densities, which can
result in tablets with poor drug or active pharmaceutical ingredient (API) content
uniformity but granulation should prevent this. Content uniformity ensures that the same
API dose is delivered with each tablet.
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Some APIs may be tableted as pure substances, but this is rarely the case; most
formulations include excipients. Normally, a pharmacologically inactive ingredient
(excipient) termed a binder is added to help hold the tablet together and give it strength.
A wide variety of binders may be used, some common ones including lactose, dibasic
calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone
polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl
methylcellulose and hydroxyethylcellulose).
Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once
swallowed, releasing the API for absorption. Some binders, such as starch and cellulose,
are also excellent disintegrants.
Advantages and Disadvantages

Tablets are simple and convenient to use. They provide an accurately measured dosage of
the active ingredient in a convenient portable package and can be designed to protect
unstable medications or disguise unpalatable ingredients. Colored coatings, embossed
markings and printing can be used to aid tablet recognition. Manufacturing processes and
techniques can provide tablets special properties, for example, sustained release or fast
dissolving formulations.
Some drugs may be unsuitable for administration by the oral route. For example, protein
drugs such as insulin may be denatured by stomach acids. Such drugs cannot be made
into tablets. Some drugs may be deactivated by the liver when they are carried there from
the gastrointestinal tract by the hepatic portal vein (the "first pass effect"), making them
unsuitable for oral use. Drugs which can be taken sublingually are absorbed through the
oral mucosae, so that they bypass the liver and are less susceptible to the first pass effect.
The oral bioavailability of some drugs may be low due to poor absorption from the
gastrointestinal tract. Such drugs may need to be given in very high doses or by injection.
For drugs that need to have rapid onset, or that have severe side effects, the oral route
may not be suitable. For example salbutamol, used to treat problems in the pulmonary
system, can have effects on the heart and circulation if taken orally; these effects are
greatly reduced by inhaling smaller doses direct to the required site of action. A
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proportion of the population have difficulties swallowing tablets either because they just
don't like taking them or because their medical condition makes it difficult for them
(dysphagia, vomiting). In such instances it may be better to consider alternative dosage
form or administration route.
Tablet Properties
Tablets can be made in virtually any shape, although requirements of patients and
tableting machines mean that most are round, oval or capsule shaped. More unusual
shapes have been manufactured but patients find these harder to swallow and they are
more vulnerable to chipping or manufacturing problems.
Tablet diameter and shape are determined by the machine tooling used to produce them -
a die plus an upper and a lower punch are required. This is called a station of tooling. The
thickness is determined by the amount of tablet material and the position of the punches
in relation to each other during compression. Once this is done, we can measure the
corresponding pressure applied during compression. The shorter the distance between the
punches, thickness, and the greater the pressure applied during compression and
sometimes the harder the tablet. Tablets need to be hard enough that they don't break up
in the bottle, yet friable enough that they disintegrate in the gastric tract.
Tablets need to be strong enough to resist the stresses of packaging, shipping and
handling by the pharmacist and patient. The mechanical strength of tablets is assessed
using a combination of (i) simple failure and erosion tests and (ii) more sophisticated
engineering tests. The simpler tests are often used for quality control purposes, whereas
the more complex tests are used during the design of the formulation and manufacturing
process in the research and development phase. Standards for tablet properties are
published in the various International Pharmacopeias (USP/NF, EP, JP, etc.). The
hardness of tablets is the principle measure of mechanical strength. Hardness is tested
using a tablet hardness tester. The units for hardness have evolved since the 1930s, but
are commonly measured in kilograms per square centimeter. Models of tester include the
Monsanto (or Stokes) Hardness Tester from 1930, the Pfizer Hardness Tester from 1950,
the Strong Cob Hardness Tester and the Heberlain (or Schleeniger) Hardness Tester.
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Lubricants prevent ingredients from clumping together and from sticking to the tablet
punches or capsule filling machine. Lubricants also ensure that tablet formation and
ejection can occur with low friction between the solid and die wall, as well as between
granules, which helps in uniform filling of the die.
Common minerals like talc or silica and fats, e.g. vegetable stearin, magnesium stearate
or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsule.
Manufacture of the Tableting Blend

In the tablet pressing process, the main guideline is to ensure that the appropriate amount
of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a
sufficiently homogenous mix of the components cannot be obtained with simple blending
processes, the ingredients must be granulated prior to compression to assure an even
distribution of the active compound in the final tablet. Two basic techniques are used to
granulate powders for compression into a tablet: wet granulation and dry granulation.
Powders that can be mixed well do not require granulation and can be compressed into
tablets through direct compression.
Wet Granulation
Wet granulation is a process of using a liquid binder to lightly agglomerate the powder
mixture. The amount of liquid has to be properly controlled, as over-wetting will cause
the granules to be too hard and under-wetting will cause them to be too soft and friable.
Aqueous solutions have the advantage of being safer to deal with than solvent-based
systems but may not be suitable for drugs which are degraded by hydrolysis.
Procedure
1. The active ingredient and excipients are weighed and mixed.
2. The wet granulate is prepared by adding the liquid binderadhesive to the powder
blend and mixing thoroughly. Examples of binders/adhesives include aqueous
preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as
methyl cellulose, gelatin, and povidone.
3. Screening the damp mass through a mesh to form pellets or granules.
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4. Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most

commonly used.
5. After the granules are dried, they are passed through a screen of smaller size than the
one used for the wet mass to create granules of uniform size.
Low shear wet granulation processes use very simple mixing equipment and can take a
considerable time to achieve a uniformly mixed state. High shear wet granulation
processes use equipment that mixes the powder and liquid at a very fast rate, and thus
speeds up the manufacturing process. Fluid bed granulation is a multiple-step wet
granulation process performed in the same vessel to pre-heat, granulate and dry the
powders. It is used because it allows close control of the granulation process.
Advantages
(a) permits mechanical handling of powders without loss of mix quality:
(b) improves the flow of powders by increasing particle size and sphericity:
(c) increases and improves the uniformity of powder density:
(d) improves cohesion during and after compaction:
(e) reduces air entrapment:
(f) reduces the level of dust and cross-contamination:
(g) allows for the addition of a liquid phase to powders (wet process only): and
(h) Makes hydrophobic surfaces hydrophilic.
Limitation of Wet Granulation
i) The greatest disadvantage of wet granulation is its cost. It is an expensive process
because
of labor, time, equipment, energy and space requirements.
ii) Loss of material during various stages of processing.
iii) Stability may be major concern for moisture sensitive or thermo labile drugs.
iv) Multiple processing steps add complexity and make validation and control difficult.
v) An inherent limitation of wet granulation is that any incompatibility between
formulation
components is aggravated.
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Dry Granulation
Dry granulation processes create granules by light compaction of the powder blend under
low pressures. The compacts so-formed are broken up gently to produce granules
(agglomerates). This process is often used when the product to be granulated is sensitive
to moisture and heat. Dry granulation can be conducted on a tablet press using slugging
tooling or on a roll press called a roller compactor. Dry granulation equipment offers a
wide range of pressures to attain proper densification and granule formation. Dry
granulation is simpler than wet granulation, therefore the cost is reduced. It is the least
desirable of all methods of granulation. However, dry granulation often produces a higher
percentage of fine granules, which can compromise the quality or create yield problems
for the tablet. Dry granulation require drugs or excipients with cohesive properties and a
'dry binder' may need to be added to the formulation to facilitate the formation of
granules. The other method is to precompress the powder with pressure rolls using a
machine such as Chilosonator.
Granule Lubrication
After granulation, a final lubrication step is used to ensure that the tableting blend does
not stick to the equipment during the tableting process. This usually involves low shear
blending of the granules with a powdered lubricant, such as magnesium stearate or stearic
acid.
Roller Compaction
The compaction of powder by means of pressure roll can also be accomplished by a

machine called chilsonator. Unlike tablet machine, the chilsonator turns out a compacted
mass in a steady continuous flow. The powder is fed down between the rollers from the
hopper which contains a spiral auger to feed the powder into the compaction zone. Like
slugs, the aggregates are screened or milled for production into granules. Use: Use in the
production of directly compressible excipients, the compaction of drugs and drug
formulations, the granulation of inorganic materials, the granulation of dry herbal
material and the production of immediate/sustained release formulations.
Processing Step
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Weighing of raw material-screening-mixing-compression to slugs-milling-mixing-

compression to finished tablets.
Advantages
The main advantages of dry granulation or slugging are that it uses less equipments and
space. It eliminates the need for binder solution, heavy mixing ]equipment and the costly
and time consuming drying step required for wet granulation. Slugging can be used for
advantages in the following situations:
(i) For moisture sensitive material.

(ii) For heat sensitive material.
(iii) For improved disintegration since powder particles are not bonded together by
a binder.
Disadvantages
i) It requires a specialized heavy duty tablet press to form slug.
ii) It does not permit uniform colour distribution as can be.
iii) Achieved with wet granulation where the dye can be incorporated into binder
liquid.
iv) The process tends to create more dust than wet granulation, increasing the
potential
contamination.
The Direct Compression Process
This method is used when a group of ingredients can be blended and placed in a tablet
press to make a tablet without any of the ingredients having to be changed. This is not
very common because many tablets have active pharmaceutical ingredients which will
not allow for direct compression due to their concentration or the excipients used in
formulation are not conducive to direct compression. Granulation is the process of
collecting particles together by creating bonds between them. There are several different
methods of granulation. The most popular, which is used by over 70% of formulation in
tablet manufacture is wet granulation. Dry granulation is another method used to form
granules.
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Advantages of Direct Compression

1. Cost Effectiveness- The prime advantage of direct compression over wet granulation
is economic since the direct compression requires fewer unit operations. This means less
equipment, lower power consumption, less space, less time and less labor leading to
reduced production cost of tablets.
2. Stability- Direct compression is more suitable for moisture and heat sensitive APIs,
since it eliminates wetting and drying steps and increases the stability of active
ingredients by reducing detrimental effects. Changes in dissolution profiles are less likely
to occur in tablets made by direct compression on storage than in those made from
granulations. This is extremely important because the official compendium now requires
dissolution specifications in most solid dosage forms.
3. Faster Dissolution- Disintegration or dissolution is the rate limiting step in absorption

in the case of tablets of poorly soluble API prepared by wet granulation. The tablets
prepared by direct compression disintegrate into API particles instead of granules that
directly come into contact with dissolution fluid and exhibits comparatively faster
dissolution.
4. Less Wears and Tears of Punches- The high compaction pressure involved in the
production of tablets by slugging or roller compaction can be avoided by adopting direct
compression. The chances of wear and tear of punches and dies are less.
5. Simplified Validation- Materials are "in process" for a shorter period of time,
resulting in less chance for contamination or cross contamination, and making it easier to
meet the requirement of current good manufacturing practices. Due to fewer unit
operations, the validation and documentation requirements are reduced. Due to the
absence of water in granulation, chance of microbial growth is minimal in tablets
prepared by direct compression.
Limitations of Direct Compression
1. Segregation- Direct compression is more prone to segregation due to the difference in

density of the API and excipients. The dry state of the material during mixing may induce
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static charge and lead to segregation. This may lead to the problems like weight variation
and content uniformity.
2. Cost- Directly compressible excipients are the speciality products produced by

patented spray drying, fluid bed drying, roller drying or co-crystallization Hence, the
products are relatively costly than the respective raw materials.
3. Low Dilution Potential- Most of the directly compressible materials can

accommodate only 30-40 % of the poorly compressible active ingredients like
acetaminophen that means the weight of the final tablet to deliver the 500 mg of
acetaminophen would be more than 1300 mg. The large tablets may create difficulty in
swallowing.
4. Re-workability- All the spray-dried directly compressible adjutants show poor rework
ability since on preparation of tablets the original spherical nature of the excipient
particles is lost. API that has poor flow properties and/or low bulk density is difficult to
process by direct compression.
5. Lubricant Sensitivity- Lubricants have a more adverse effect on the filler, which
exhibit almost no fracture or shear on compression (e.g. starch 1500). The softening
effects as well as the hydrophobic effect of alkaline stearates can be controlled by
optimizing the length of blending time to as little as 2-5 min.
6. Variation in Functionality- There is a lack of awareness in some situations that the

excipient behave differently, depending upon the vendor so much so that substitution
from one source to that of another is not possible. Hence, there is a need for greater
quality control in purchasing of raw material to assure batch uniformity.
Manufacture of the Tablets
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Figure 1
Tablets that Failed due to Capping and Lamination Compared to a Normal Tablet
Whatever process is used to make the tableting blend, the process of making a tablet by
powder compaction is very similar. First, the powder is filled into the die from above.
The mass of powder is determined by the position of the lower punch in the die, the
cross-sectional area of the die and the powder density. At this stage, adjustments to the
tablet weight are normally made by repositioning the lower punch. After die filling, the
upper punch is lowered into the die and the powder is uniaxially compressed to a porosity
of between 5 and 20%. The compression can take place in one or two stages (main
compression and sometimes, pre-compression or tamping) and for commercial
production occurs very fast (50050 ms per tablet). Finally, the upper punch is pulled up
and out of the die (decompression) and the tablet is ejected from the die by lifting the
lower punch until its upper surface is flush with the top face of the die. This process is
repeated for each tablet.
Common problems encountered during tablet manufacturing operations include:
1. Fluctuations in tablet weight, usually caused by uneven powder flow into the die due
to poor powder flow properties.
2. Fluctuations in dosage of the active pharmaceutical ingredient, caused by uneven

distribution of the API in the tableting blend (either due to poor mixing or separation
in process.
3. Sticking of the powder blend to the tablet tooling, due to inadequate lubrication, worn
or dirty tooling, or a sticky powder formulation
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4. Capping, lamination or chipping. This is caused by air being compressed with the
tablet formulation and then expanding when the punch is released: if this breaks the
tablet apart, it can be due to incorrect machine settings, or due to incorrect
formulation: either because the tablet formulation is too brittle or not adhesive
enough, or because the powder being fed to the tablet press contains too much air (has
too low bulk density).
5. Capping can also occur due to high moisture content.
Tablet Compaction Simulator

Tablet formulations are designed and tested using a laboratory machine called a Tablet
Compaction Simulator or Powder Compaction Simulator. This is a computer controlled
device that can measure the punch positions, punch pressures, friction forces, die wall
pressures, and sometimes the tablet internal temperature during the compaction event.
Numerous experiments with small quantities of different mixtures can be performed to
optimize a formulation. Mathematically corrected punch motions can be programmed to
simulate any type and model of production tablet press. Initial quantities of active
pharmaceutical ingredients are very expensive to produce and using a Compaction
Simulator reduces the amount of powder required for product development.
Figure 2.The Tablet Pressing Operation
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Figure 3. An Old Cad mach Rotary Tablet Press
Tablet presses, also called tableting machines, range from small, inexpensive bench-top
models that make one tablet at a time (single-station presses), with only around a half-ton
pressure, to large, computerized, industrial models (multi-station rotary presses) that can
make hundreds of thousands to millions of tablets an hour with much greater pressure.
The tablet press is an essential piece of machinery for any pharmaceutical and
nutraceutical manufacturer. Common manufacturers of tablet presses include Stokes,
Fette Compacting, Korsch, Kikusui, Manesty, B&D, PTK, IMA and Courtoy. Tablet
presses must allow the operator to adjust the position of the lower and upper punches
accurately, so that the tablet weight, thickness and density can each be controlled. This is
achieved using a series of cams, rollers, and/or tracks that act on the tablet tooling
(punches). Mechanical systems are also incorporated for die filling and for ejecting and
removing the tablets from the press after compression. Pharmaceutical tablet presses are
required to be easy to clean and quick to reconfigure with different tooling, because they
are usually used to manufacture many different products. There are 2 main standards of
tablet tooling used in pharmaceutical industry: American standard TSM and European
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standard EU. TSM and EU configurations are similar to each other but cannot be
interchanged.
Tablet Coating
Many tablets today are coated after being pressed. Although sugar-coating was popular in
the past, the process has many drawbacks. Modern tablet coatings are polymer and
polysaccharide based, with plasticizers and pigments included. Tablet coatings must be
stable and strong enough to survive the handling of the tablet, must not make tablets stick
together during the coating process and must follow the fine contours of embossed
characters or logos on tablets. Coatings are necessary for tablets that have an unpleasant
taste and a smoother finish makes large tablets easier to swallow. Tablet coatings are also
useful to extend the shelf-life of components that are sensitive to moisture or oxidation.
Special coatings (for example with pearlescent effects) can enhance brand recognition.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining,
an enteric coating can be used, which is resistant to stomach acid and dissolves in the less
acidic area of the intestines. Enteric coatings are also used for medicines that can be
negatively affected by taking a long time to reach the small intestine, where they are
absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the
gastrointestinal tract. Some drugs will be absorbed better at different points in the
digestive system. If the highest percentage of absorption of a drug takes place in the
stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of
absorption is best in the large intestine or colon, then a coating that is acid resistant and
dissolves slowly would be used to ensure it reached that point before dispersing.
There are two types of coating machines used in the pharmaceutical industry: coating
pans and automatic coaters. Coating pans are used mostly for sugar coating of pellets.
Automatic coaters are used for all kinds of coatings; they can be equipped with remote
control panel, dehumidifier, and dust collectors. The explosion-proof design is required
for alcohol containing coatings.
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Figure 4 Second generation late 1970s model
A simple to operate machine had now been developed to accurately and quickly count
prescription medications. One of the first commercially available tablet counters in use
was the KL7. That first model was soon followed by technology advancements which
resulted in the more compact KL8 model. The price of such equipment in 1980 was
around 1,300. This substantial investment in new technology was a major consideration
for many pharmacies. Eventually the pharmacy community adopted the use of a counting
machine as a superior method to hand-counting medications. These devices became
known as tablet counter, capsule counter, pill counter, or drug counter.
The new counting technology replaced manual methods in many industries such as,
vitamin and diet supplement manufacturing. Technicians needed a small, affordable
device to count and bottle medications. In England and America, the 1980s and 1990s
saw new the development of high-speed machines for counting and bottle filling, such as
the KLX. Like their pharmacy-based counterparts, these industrial units were designed to
be fast and simple to operate, yet remain small and cost effective.
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Figure 5 Kirby Lester KL25 counter and prepackaging device
In America, in the late 1990s/early 2000s a new type of tablet counter appeared. The
KL15e was simple, small, inexpensive, and offered outstanding levels of counting
accuracy. At the turn of the millennium technical advances saw the design of a new breed
of counters with a verification system. With an onboard computer, displaying photo
images of medications to assist the pharmacist or pharmacy technician to verify that the
correct medication was being dispensed. In addition, a database for storing all
prescriptions that were counted on the device.
Pictured here is an early American type of integrated counter and packaging device. This
machine was a third generation step in the evolution of pharmacy automated devices.
Later models held pre-counted containers of commonly-prescribed medications.
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Global variations
Figure. 6 Tablets in a blister pack
In the EU member states legislation was introduced in 1998 which had a major effect on
UK Pharmacy operations. It effectively prohibited the use of tablet counters for counting
and dispensing bulk packaged tablets. Both usage and sales of the machines in the UK
declined rapidly as a result of the introduction of blister packaging for medicines.
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Recent Automation in Tablet Technology

Tablet Presses
Korsch XL 800 Tablet Press
Manufacturer: Korsch
Model: XL 800
Product Code: 249713
The Korsch XL 800 is the highest output tablet press in the world, offering a
single-layer and bi-layer capability.
Figure 7 Korsch XL 800 Tablet Press
Description
The Korsch XL 800 is the highest output tablet press in the world, offering a single-layer
and bi-layer capability. The exchangeable turret design permits the production of any
tablet size on a single machine. The unique mechanical design isolates vibration in the
compression zone to permit the lowest noise operation, even at the higher press speeds
and compression forces. The XL 800 is a proven, reliable workhorse for high volume,
24/7 operation
Make: Korsch
Model: XL 800
Serial # K1580006
Year: 2003
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Capacity Size: B
Includes:
Spare Turret
Control Panel
Specifications:
Number of punch stations: 71
Number of compression stations: 2
Execution EU/TSM B
Main compression force max.: Rolle 250 mm: 100kN
Pre-compression force variable max.: Roll 250 mm: 100kN
Pre-compression force, alternative: Roll 110 mm: 20kN
Bi-layer-capability optional
Tablet diameter (max.): 16mm
Filling depths, single-layer max.: 18mm
Press speed: 5-90 /min
Tablet output, single-layer max. : 766,800 tabs/h
Tablet output, bi-layer max. tabs/h: 383,400
Pitch circle diameter: 840mm
Maximum height of the tablet :8.5mm
Elite 800 Manesty 75 Station Tablet Press

Manufacturer: Manesty
Model: Elite 800
Used Manesty Elite 800, 75 station bi-layer tablet press. Available with several
change parts.
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Figure 8 Rated up to 801,000 tablets per hour.

Make: Manesty
Model: Elite 800
75 Station
BB Tooling
Bi-Layer
TTS-6 Controls
Keyed Upper Punch Bores
Power Feeders
10 kn pre-compression
65 kn main compression
11 mm max tablet diameter
17 mm max depth of fill
Keyed upper punch guides
Unit comes with several other change parts such as Osmotic bi-layer,
single layer, single layer P style and various size cams,etc....
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Stokes 328 Tablet Press, 33 Station
Manufacturer: Stokes
Model: 328
The model 328 is the leading heavy-duty, high-speed compacting press. It
produces large quality compacts and tablets in various shapes from a variety of
materials. The Stokes Model 328 has a reputation for dependable, long term
operation.
Figure 9 Stokes 328 Tablet Press, 33 Stations
The Stokes 328 produces large quality compacts and tablets in various shapes from a
variety of materials making it the leading heavy-duty, high-speed compacting
press. The model 328 is the leading heavy-duty, high-speed compacting press. It
produces large quality compacts and tablets in various shapes from a variety of
materials. The Stokes Model 328 has a reputation for dependable, long term operation
with very low maintenance costs.
Make: Stokes
Model: 328
Serial #: 694045
33 Station
Keyed. Able to run round and shaped tablets.
Specifications:
Type of Tooling: 328
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Maximum Tablet dia. (in): 1.187

Turret speed range (rpm): 18-50
Output of tablet (per min): 1200-3300
Fill depth - Standard (in): 0.6875
Fill depth - Maximum (in): 1.375
Max. compression force (tons): 10
Power (H.P): 7.5
Footprint (in.): 52 x 46
Overall height (in.): 67
Net weight (lbs): 5000
Design Features:
Extremely durable press due to rugged design
Easy to operate and maintain
Replacement parts are economical
Neck-less tool design allows machine to run difficult materials
Fette P3100 Tablet Press
Manufacturer: Fette
Model: P3100
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Figure 10 Fette P3100 Tablet Press
Description
Make: Fette
Model: P3100
Serial #: 23509
Year: 1986
Specifications:
45 station
With pre-compression
B tooled
With force feeder
DataControl 2 controls
PAC2 Tablet Press Weight Control & Reject System
A universal tablet press control unit, that is designed to provide automatic weight control
and reject capability. This system utilizes Digital Signal Processing & Allen- Bradley
ContolLogix PLC technology to meet rigid industry standards for compliance, ease of
use, reliability and performance
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Figure 11 PAC2 Tablet Press Weight Control & Reject System
Key features include:
Main compression trend
Individual tool pressure display
Tablet reject history
Product and press recipes
Automatic setup
Weight feedback
Hardness adjustment
Lot summary and event history reports
Global status menu
TCS Tablet Press

Control System
The TCS modular system incorporates Allen- Bradley ContolLogix PLC technology to
control tablet weight via force feedback and reject out of specication tablets on any
rotary tablet press. Key features include:
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Figure 12 TCS Tablet Press
Modular system
No electronic records
User friendly interface that is easy to navigate and operate
A detailed I/O and calibration screen enables operators to quickly

troubleshoot and/or calibrate the system
Pressure control for automatic weight adjustment rejected tablet
monitoring
Individual tool pressure display I/O diagnostics screen calibration
screen
Turret & feeder adjustment simple screen navigation no electronic
records
KL1 Kirby Lester's smallest, fastest tablet counter ever
From the same company that invented the pharmacy tablet counter comes the KL1, Kirby
Lester's smallest and fastest counter. Its compact size fits into even the most crowded
workspace. With the world-renowned Kirby Lester counting technology inside, the KL1
counts any tablet or capsule quickly, conveniently and accurately.
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Figure 13 KL1 Kirby Lester's smallest, fastest tablet counter ever
Compact design inspired by feedback and input
from our retail pharmacy advisory panel and customers
Fast operation with no calibration or adjustments needed for different products

(pour through at a rate of 15/18 tablets per second)
World-renowned counting technology inside
Inventory mode: keeps count when the tray is emptied
Ergonomically designed tray with left/right pouring
Simple cleaning
Unique vial size indicator displays the correct container size for every batch
counted
Full 1-year warranty
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KL1Plus Streamlined Counting Plus Verification Device
Think of a great tablet counter with a safety net...that's the KL1Plus. It is all a
retail/outpatient pharmacy needs to count medications while safeguarding against errors.
The KL1Plus combines the best-selling KL1 tablet counter with streamlined verification
software. It's small enough to fit into your hand, but it delivers so much value and peace
of mind. The KL1Plus ensures that all pharmacy orders (tablets, capsules and unit-of-use
items) are verified so the patient receives the right medication, dosage and quantity every
time. The pharmacy technician simply barcode-scans the patient's Rx label, then scans the
corresponding stock bottle or package to ensure there is a match. Eliminating dispensing
errors really is that simple with the KL1Plus.0
Figure 14 KL1Plus Streamlined Counting Plus Verification Device
For pharmacies that want more than just a tablet counter, but less than fully
loaded dispensing software or robotics.
Bar code scanning provides verification for all dispensed medications (tablets,
capsules and unit of use). The KL1Plus software alerts the technician to a
potential error.
Orders are verified and filled in less time than traditional hand-counting.
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Fits any crowded workspace about the same footprint as a counting tray (about
7" wide x 12" deep x 13" high)
Can interface with your pharmacy management system for real-time data
exchange, or operate stand-alone. Both modes include easy-to-use verification
software.
Filled orders can be retrieved quickly on the touch-screen to validate dispense

information.
Can operate as a simple KL1 tablet counter if desired.
Fast operation with no calibration or adjustments needed for different products

(pour through at a rate of 15/18 tablets per second)
World-renowned counting technology inside
Inventory mode: keeps count when the tray is emptied; ideal for 90-day fills
Ergonomically designed tray with left/right pouring
KL100 Streamlined robotic dispensing for medium to high volume pharmacies

with "FillSafe " security system
27
Figure 15 KL100
The KL100 brings a new level of efficiency and safety to busy retail/outpatient
pharmacies and central fill facilities. Fully 50 percent (or more) of a pharmacy's total
daily orders can be easily dispensed in a robot that's less than 5 feet deep. The
streamlined KL100 is smaller than most pharmacy robots and easily fits into an existing
floor plan without the need for renovation. But by automating 100 of a pharmacy's top-
moving tablets and capsules, the KL100 provides an elevated capacity for pharmacies
wanting to automate a higher number of SKUs. With the KL100 managing the bulk of
your prescriptions, your staff can then focus on important initiatives that drive your
pharmacy forward.
New! The exclusive "FillSafe " system elevates security levels in the KL100,
preventing any unapproved cassette replenishment. The KL100 is proof-positive that you
don't need an oversized, overpriced pharmacy robot to manage the majority of your daily
prescriptions quickly, safely and accurately.
28
Tour the KL100
Free up valuable time - The KL100 automatically dispenses the bulk of your
prescriptions automatically. Your pharmacy staff is freed up to concentrate on
important priorities like customer service, adherence, MTM or other initiatives
that help the pharmacy's efficiency, profitability and expansion.
Fully Automate 50% (or More) of Your Total Orders - The KL100 pharmacy
robot is perfectly sized for pharmacies wanting the next level of automation to
handle a higher volume of daily scripts.
"FillSafe ": Built-In Security for Peace of Mind During Refilling - The
foolproof FillSafe security system prevents dispensing from a cassette whose
refill or return-to-stock was not authorized by a pharmacist. Cassettes are
automatically deactivated when removed.
Safety First, Without Compromising Fast Operation - Along with the

FillSafe security system (above), the KL100 is equipped with multiple
safeguards, including user fingerprint tracking, NDC barcode verification, and
more. The KL100 balances the highest security standards with the fastest
dispensing and most hassle-free operation.
Small Footprint, Big Results - Less than 5' deep, the KL100's streamlined design
eliminates the need for costly renovation.
Industry-Best Speed and Accuracy - Orders are labeled, counted and presented
in about 30 seconds. Drug-specific cassettes provide superior accuracy and speed;
gravity-feed design and adjustable cassette speed avoid the pill-jamming and
miscounting frustrations of error-prone hand-calibrated cassettes.
Flexible Vial Type and Size - The KL100 can accommodate many common vial
types and two different vial sizes. Choose the vial that suits your business.
29
User-Friendly, Easy Installation - Maintaining the KL100 takes a few minutes a

day, and loading vials, labels and medications is easy. The KL100's intuitive
software guides the technician through the simple Rx filling process. Requires
standard 110v power. No compressed air, remodeling, special wiring or
engineering are needed.
30
KL50ic/icf Small- to mid-volume packing
The KL50 (ic and icf models) is ideal for pharmaceutical and supplement manufacturing
facilities, clinical trials, check counting and other specialty applications needing small- to
mid-capacity counting and filling. The KL50ic/icf also is well-suited for manufacturing
facilities that need absolute accuracy when batch-counting identical-shaped items (e.g.,
seeds, electronic components).
Figure 16 KL50ic/icf Small- to mid-volume packing
High-speed counting system for batch verification, packing tablets, or batch-

counting identical-shaped parts
Fast, accurate counting using Kirby Lester technology (up to 1,920 parts/minute,
adjustable)
No adjustments to count different products
Small footprint, simple operation and cleaning
31
Two versions: The KL50ic holds up to 500 size-0 capsules in the bowl; the
KL50icf accommodates an additional 1,800 capsules (2 liters) in the removable
rotating hopper
Operating the KL50ic/icf is simple. Fill either the vibratory bowl (KL50ic) or rotating
hopper (KL50icf). Enter the number of parts needed per container and the number of
containers. Start the KL50. The technology quickly counts each piece, and batches are
delivered to final bottles or vials beneath the left and right exits.
With the KL50, you can adjust the counting speed, depending on the shape of the unit
being counted and your operational needs.
KL15df The classic tablet coutner, direct fill

Fast, accurate counting without adjustments for different products
Always accurate
"Gold-Standard"
Transfers the counted batch directly to a final container

The KL15df counts all shapes and sizes of tablets and capsules without adjustments or
moving parts. A unique vial size indicator displays the correct container size for every
batch counted. The ergonomic design speeds counting, at a rate of 15-18 tablets per
second. With its direct fill chute, the KL15df transfers counted tablets directly into a vial
or bottle.
32
Figure 17KL15df The classic tablet coutner, direct fill
KL15e Technical Specifications

Weight: 20.4lb (9.3kg)
Size: 19.5"H x 17"D x 9"W (49.5cm x 43.2cm x 22.9cm)
Power: 110V, 60Hz and 220V, 50Hz (voltage internally switchable but factory set)
Throughput: 15-18 tablets/second
Maximum Tablet Size: 0.86" long (22mm) and 0.74" wide (19mm)
Minimum tablet size: 0.125" diameter (3.175mm)
Romaco Kilian KTP 180X Tablet Press
The KTP 180X is the ideal rotary tablet press for applications in the pharmaceutical
industry from R&D through clinical batches to small scale production.
The machine is available in two configurations:
KTP 180X (Production)

KTP 180X (Laboratory)
33
Figure 18 KILIAN KTP 180X
Benefits of the KTP 180X
Suitable for R&D applications or small scale production

Unique scale-up functionality
Extensive, user-tailored data capturing capabilities in the R&D configuration
Handling, operation and robust design equal to that of a large-volume production
machine
Operation via a 12" integrated touch panel (HMI)
Data acquisition system integrated in the operating software
Small footprint
Technical Highlights
Interchangeable die table

Mixed turrets available for B+D tooling
Easy access to all product-contacted parts
Patented, wear-free brake magnets
34
Individual tablet rejection system using compressed air

Fully automated machine including weight control
R&D machine version monitors upper and lower compression forces, ejection
force, pre-compression force, tablet scraping force, upper and lower punch
displacement
Magnesium stearate spraying system available (PKB)
Paddle force feeding with two paddles available as an option
35
KILIAN KTS1000
Kilian KTS1000
The KTS1000 is a versatile and powerful solution offering state-of-the-art performance in
pharmaceutical, cosmetics or food applications.
The machine is available in two configurations:
2L (Mono/bi-layer machine)
3L (Mono/bi-layer/triple-layer tabletpress)
Figure 19 KILIAN KTS1000

Applications
Chemicals (e.g. dishwasher tabs, detergent tabs, salt tablets, fertilisers, pesticides,
naphthalene, paint)
Food (e.g. soup cubes, sweeteners, sugar, dextrose, fructose, food tablets)
Sintered metals, ceramic, electrical components (e.g. carbide, thermoplastics,
airbags, coal products)
Cosmetics (e.g. denture cleaners, bath salts)
36
SPECIAL TABLET OUTLET

Benefits of the KTS1000 Tablet Press
Long service life due to the extremely robust machine design
High overall equipment effectiveness
Suitable for abrasive products
Minimal product loss after starting / stopping
Dedicated tooling for products that are difficult to compress
Technical Highlights
Three pressing stations allot triple-layer tableting

Large 840 mm pitch circle, designed for high output
Hydraulic overpressure protection
Patented, wear-free punch brake magnets for constant re-dosing
Different fill shoe systems enable optimal powder feeding
Special product feeding system for poorly flowing products
Optimized product feeding system suitable for sticky products
37
38
Review of Literature
Bhanja S et al., (2010), formulated and evaluated of mucoadhesive buccal tablets
containing promethazine to circumvent the first pass effect and to improve its
bioavailability with reduction in dosing frequency and dose related side effects. The
tablets were prepared by direct compression method. Eight formulations were developed
with varying concentrations of polymers like carbopol 934, polyethylene oxide and
hydroxy propyl methyl cellulose. The tablets were tested for weight variation, hardness,
surface pH, drug content uniformity, swelling index and bio adhesive strength and in-
vitro drug dissolution study. The in vitro release kinetics studies reveal that all
formulations fits well with zero order kinetics followed by korsmeyer-peppas, first order
and then higuchis model and the mechanism of drug release was non-fickian diffusion.
Argemi A et al., (2010), prepared and characterized of transdermal patches of

promethazine. A mixture of ethylene vinyl acetate and Eudragit ( E100) (80:20, w/w) was
used as a polymeric matrix to obtain a thin membrane. Patches synthesized in this way
were loaded with about 1% promethazine. The drug release and diffusion process through
a membrane have been studied chromatographically using a Franz diffusion cell. Results
have shown that a sustained delivery for more than 24 h was obtained.
Adhikari SN et al., (2010), developed buccal patches for the delivery of

promethazine using sodium alginate with various hydrophilic polymers like carbopol 934
P, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose in various
proportions and combinations were fabricated by solvent casting technique. Various
physicomechanical parameters like weight variation, thickness, folding endurance, drug
content, moisture content, moisture absorption, and various ex vivo mucoadhesion
parameters like mucoadhesive strength, force of adhesion and bond strength were
evaluated. An in vitro drug release study was designed and it was carried out using
39
commercial semipermeable membrane. All these fabricated patches were sustained for 24
h and obeyed first-order release kinetics.
Patel RS and Poddar SS, (2009), prepared and evaluated of mucoadhesive buccal
patches for the controlled systemic delivery of promethazine theoclate to avoid first pass
hepatic metabolism. The developed patches were evaluated for the physicochemical,
mechanical and drug release characteristics. The patches showed desired mechanical and
physicochemical properties to withstand environment of oral cavity. The in vitro release
study showed that patches could deliver drug to the oral mucosa for a period of 7 h. The
patches exhibited adequate stability when tested under accelerated conditions.
Sekhar K et al., (2008), described buccal permeation of promethazine theoclate and its
transbuccal delivery using mucoadhesive buccal patches. Permeation of drug was
calculated in vitro using porcine buccal membrane and in vivo in healthy humans. Buccal
formulations were developed with hydroxyethylcellulose and evaluated for in vitro
release, moisture absorption, mechanical properties and bioadhesion. Optimized
formulation was subjected for bioavailability studies in healthy human volunteers.
Khankari et al., (2001), formulated a rapidly dissolving robust dosage form. The
invention was directed to a hard tablet that can be stored, packaged and processed in
bulk. The tablet dissolved rapidly in the mouth of the patient with a minimum of grit. The
tablet was created from an active ingredient mixed into a matrix of no direct compression
filler and a relatively high lubricant content
40
Future Prospective
Various companies are currently developing a range of remote tablet counters,
verification systems and pharmacy automation components to improve the accuracy,
safety, speed and efficiency of medication dispensing. Products that are used in retail,
mail order, hospital outpatient and specialty pharmacies as well as industrial settings such
as manufacturing and component factories. These advanced systems will continue to
provide accurate counting without the need for adjustment or calibration when counting
in different production environments.
Pictured here is a modern (2010) remote controlled tablet hopper mechanism for use with
bulk packaged individual tablets or capsules. In the UK these items are more suited to
Hospital Pharmacies, where the issue of E.U. blister packaging regulations relating to
medicine packaging does not apply. Also pictured is another version of an automated
machine that does not allow unauthorised interference to the internal store of drugs (A
useful security feature in a large pharmacy with public access).
41
Figure 20 Remote tablet counter / dispenser Figure 21 Remote dispensing Unit
Repackaging Process and Stability Data

The transient or definitive displacement of the solid oral form from the original
atmosphere to enter a repackaging process, sometimes automated, is likely to play a
primary role in the pharmaceutical controversy in some countries. However, the solid oral
dose is to be repackaged in materials with defined quality. Considering these data, a
review of the literature for determination of conditions for repackaged drug stability
according to different international guidelines is presented by F Lagrange.
42
Conclusion:
Recent Advances in tableting technology are a vast area for discussion. Tablet formula,
the excipients used, the production process starting from receipt of raw material through
the intermediate processing steps to the finished product at high speeds; the entire
documentation too is seeing automation. Reproducibility, accuracy and consistency are
being achieved due to the development in tableting science. Contribution to quality by
design is being made possible ultimately contributing to quality, safety and efficacy of the
drug product.
Recently RDFs have gained popularity as dosage forms for the mouth fresheners.
Meanwhile pharmaceutical industries have recognized their potential for delivering
medicinal products and has launched several products for the OTC market using this
technology. The fast dissolving thin film are hardly described and investigated in
literature, but seem to be an ideal dosage form for use in young children, especially in
geriatric and pediatric patients. They combine the greater stability of a solid dosage form
and the good applicability of a liquid. Due to lack of standar.
43
References
1. United States Pharmacopeia, United States Pharmacopeia / National
Formulary (USP25/NF20). 2002, Rockville, MD: United States Pharmacopeia
Convention Inc.
2. Hiestand, E.N., 2003. Mechanics and physical principles for powders and
compacts, SSCI Inc., West Lafayette, In, USA
3. Kibbe, A.H., ed. Handbook of Pharmaceutical Excipients. 3rd Edition ed.

2000, American Pharmaceutical Association & Pharmaceutical Press:
Washington, DC & London, UK.
4. Melissa Elder (January 2008). "Pharmacy Automation: Technologies and

Global Markets BCC00098". Report. Business Communications Company.
Retrieved 6 March 2010.
5. Jordans Business Information Services (2008). "Basic company details

for KIRBY DEVON LIMITED:". Jordans Ltd. Retrieved 6 March 2010.
6. Christopher J Thomsen (9 November 2004). "Pharmacy Automation-

Practical Technology Solutions for the Pharmacy". Business briefing : US
Pharmacy review 2004. The Thompson Group. Retrieved 5 March 2010.
7. John Kirby Filed 8 September 1970 (3 July 1974). "Patent 1358378".

COUNTING MACHINES - Patent GB1358378(A). DTI Data Networks LLC.
Retrieved 18 March 2010.
8. United States Patent Office (29 January 1974). "Patent 3789194".

RELATING TO COUNTING MACHINES. Freepatentsonline.com. Retrieved 6
March 2010.
44
9. Occupational medicine-New Products Occup Med (Lond).1981; 31: 40".

Oxford University Press-Oxford Journals. 1981. Retrieved 5 March 2010.
10. Liz Parks (November/December 2003 issue). "Market Survey of

Pharmacy Technology and Automation in Retail and Outpatient Pharmacy".
Retail Pharmacy Management. The Thomsen group. Retrieved 6 March 2010.
Check date values in
11. An Efficiency Analysis of the Kirby Lester KL16df Automatic Tablet and
Capsule Counting System". Pharmacy Automation. The ThomsenGroup Inc.
2004. Retrieved 5 March 2010.
12. "Labels, patient information leaflets and packaging for medicines". The
Medicines and Healthcare products Regulatory Agency (MHRA). 2010. Retrieved
8 March 2010.
13. Melissa Elder (March 2008). "Pharmacy Automation: Technologies and

Global Markets IAS026A". BCC Research. Retrieved 6 March 2010.
14. American Capital exited its investment in Kirby Lester, LLC in the third
quarter of 2007". American Capital Limited. 19 September 2005. Retrieved 12
March 2010.
15. Kevin Welch (November/December 2009 Vol. 29, No. 6). "Looking
Ahead: What's Coming in 2010". Pharmacy Delivery Technology A Primer.
Computer Talk for the Pharmacist. Retrieved 5 March 2010. Check date values in:
|date= (help)
16. Flynn EA, Barker KN, Carnahan BJ (2003). "National observational

study of prescription dispensing accuracy and safety in 50 pharmacies". Journal
of the American Pharmaceutical Association 43 (2):
17. Lagrange F: [Current perspectives on the repackaging and stability of

solid oral doses].
45

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RECENT ADVANCEMENT IN DRUG TECHNOLOGY

A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances

Advantages and Disadvantages

Manufacture of the Tableting Blend

4. Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most

The compaction of powder by means of pressure roll can also be accomplished by a

Weighing of raw material-screening-mixing-compression to slugs-milling-mixing-

(i) For moisture sensitive material.

The Direct Compression Process

Advantages of Direct Compression

3. Faster Dissolution- Disintegration or dissolution is the rate limiting step in absorption

Limitations of Direct Compression

1. Segregation- Direct compression is more prone to segregation due to the difference in

2. Cost- Directly compressible excipients are the speciality products produced by

3. Low Dilution Potential- Most of the directly compressible materials can

6. Variation in Functionality- There is a lack of awareness in some situations that the

Manufacture of the Tablets

Common problems encountered during tablet manufacturing operations include:

2. Fluctuations in dosage of the active pharmaceutical ingredient, caused by uneven

5. Capping can also occur due to high moisture content.

Tablet Compaction Simulator

Figure 2.The Tablet Pressing Operation

Figure 3. An Old Cad mach Rotary Tablet Press

Figure 4 Second generation late 1970s model

Figure 5 Kirby Lester KL25 counter and prepackaging device

Figure. 6 Tablets in a blister pack

Recent Automation in Tablet Technology

Figure 7 Korsch XL 800 Tablet Press

Elite 800 Manesty 75 Station Tablet Press

Figure 8 Rated up to 801,000 tablets per hour.

Stokes 328 Tablet Press, 33 Station

Figure 9 Stokes 328 Tablet Press, 33 Stations

Maximum Tablet dia. (in): 1.187

Figure 10 Fette P3100 Tablet Press

PAC2 Tablet Press Weight Control & Reject System

Figure 11 PAC2 Tablet Press Weight Control & Reject System

Key features include:

Main compression trend

Individual tool pressure display

Tablet reject history

Product and press recipes

Lot summary and event history reports

Global status menu

TCS Tablet Press

Figure 12 TCS Tablet Press

User friendly interface that is easy to navigate and operate

A detailed I/O and calibration screen enables operators to quickly

KL1 Kirby Lester's smallest, fastest tablet counter ever

Figure 13 KL1 Kirby Lester's smallest, fastest tablet counter ever

Compact design inspired by feedback and input

from our retail pharmacy advisory panel and customers

Fast operation with no calibration or adjustments needed for different products

World-renowned counting technology inside

Inventory mode: keeps count when the tray is emptied

Ergonomically designed tray with left/right pouring

Full 1-year warranty

KL1Plus Streamlined Counting Plus Verification Device

Figure 14 KL1Plus Streamlined Counting Plus Verification Device

Filled orders can be retrieved quickly on the touch-screen to validate dispense

Can operate as a simple KL1 tablet counter if desired.

Fast operation with no calibration or adjustments needed for different products

World-renowned counting technology inside

Ergonomically designed tray with left/right pouring

KL100 Streamlined robotic dispensing for medium to high volume pharmacies