Coating of Solid Dosage Form

KLEUS College of Pharmacy JNMC Campus Belgaum, Karnataka.

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SCHEME OF PRESENTATION
Introduction
- Why Coating is Required?

Key Factors - Tablet Properties Coating techniques

- Film Coating Introduction Reasons for film Coating Film Coating materials Process controls Coating Equipment

Pelletization
Introduction Preparation

INTRODUCTION

Tablet coating

is the application of coating material to the

exterior of a tablet with the intention of conferring benefits and properties to dosage form over the uncoated variety.

Why Tablet Coating is Required?

A number of reasons can be suggested:

The core contains a material which has a bitter taste in the

mouth or has an unpleasant odor.

Coating will protect the drug from the surroundings with a view to improve its stability. Coating will increase the ease by which a tablet can be ingested by the patient. 3

CONT.

The core contains a substance which is incompatible in the presence of light and subject to atmospheric oxidation, i.e. a coating is added to improve stability. The core alone is inelegant. The active substance is colored and migrates easily to stain hands

and clothes.
The coated tablet is packed on high-speed packaging machine. Coating reduces friction and increases packaging rate. Coating can modify the drug release profile, e.g., enteric coating, osmotic pump, pulsatile delivery. 4

KEY FACTORS

Tablet Properties
Core design is extremely important!! Mechanical integrity (hardness, friability, etc.) Physico-chemical stability of the core when exposed to coating conditions (expansion or contraction, release rate, etc.)
Shape Effect!!

Coating illustrates areas on the tablet that have the highest erosion potential. Therefore, normal concave is the preferred shape for film coating.

Areas prone to surface erosion for flat, shallow concave, caplet shaped and deep concave tablets respectively as shown in fig 1. 5

CONT.

Fig 1

Twining Occurs

fig 2

Twinning less likely

TECHNIQUES

Coating Techniques
Sugar Coating Film Coating Compression Coating

Why not sugar coating?

Reasons are: Skilled manipulative process Long and vigorous Operator must be highly skilled for such coating.

COMPARISON

FILM COATING

Film coating is a process whereby a polymer based coating is

applied to the substrate such that:

- The rate of application of the coating fluid and the drying rate are carefully controlled. - The coating material is uniformly applied to the surface of the substrate. - The quality and the functionality of the applied coating are both

maximized and reproducible.

- The thickness of such a coating is usually between 20-100 m.

SCHEMETIC REPRESENTATION

10

CONT.
Film coatings are applied for the following reasons:

- Their aesthetic qualities

- Improving product stability and robustness - Enhancing flavor attributes - Facilitating ingestion and modifying drug release

characteristics.

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CONT.
Film coating is performed by two types,

1. Aqueous film coating (generally water is used as a solvent)

High quality aqueous film coating must be smooth, uniform and adhere satisfactorily to the tablet surface and ensure chemical stability of a drug.

Non-functional Coating

12

CONT.

2. Non aqueous film coating (generally organic solvent are used.)

(Functional Coating) (Modified-Release Coating)

Some problems are associated with the non aqueous film coating like employee safety (its dangerous, it smells, and its not good to breathe.) atmosphere pollution etc. But key problem is with the approval of the regulatory authority.

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FILM COATING MATERIALS

An ideal film coating material should have the Following

attributes:

Solubility in solvent of choice for coating Preparation

Capacity to produce an elegant looking product

Essentially no color, taste or odor Compatibility with common coating solution additives Ease of printing procedure on high speed equipment No toxicity and no pharmacological activity

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Polymer
Capable of forming smooth thin films reproducible under conventional coating conditions and applicable to variety of tablet shapes (7-18%)

Non-enteric Polymers
Hypromellose Hydroxyethyl cellulose Hydroxyethylmethyl Cellulose Carboxymethylcellulose sodium Hydroxypropyl Cellulose Ethyl Cellulose Polyethylene Glycol

Enteric Polymers
Hypromellose phthalate Polyvinyl acetate phthalate Cellulose acetate phthalate Polymethacrylates Shellac

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IDEAL CHARACTERISTICS OF A FILM COATING POLYMER

Solubility
For conventional film coating the polymer should have good solubility in aqueous fluids to facilitate the dissolution of the active ingredient from the finished dosage form. However, where a modified-release action is required then a polymer system of low water solubility or permeability will be chosen.

16

16

CONT.
Viscosity
polymers should have a low viscosity for a given concentration. This will permit the easy, trouble- free spraying of their solutions in industrial film coating equipment.

Permeability
Film coating can be used to optimize the shelf-life of a tablet preparation, as some polymers are efficient barriers against the permeability of water vapor or other atmospheric gases. These properties vary widely between the individual polymers

17

17

CONT.
Mechanical properties polymer chosen for a film coat formulation must be: one with adequate strength to withstand the impact and abrasion

encountered in normal handling. Insufficient coating strength will be demonstrated by the development of cracks and other imperfections in the coating. It should be mentioned that the polymer chosen must also comply with the relevant regulatory and pharmacopoeial requirements current in the intended marketing area.

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CONT

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Plasticizer
Plasticizers are simply relatively low molecular weight materials which have the capacity to alter the physical properties of the polymer to render it more useful in performing its function as a film-coating material. Concentration (0.5-2.0 %)

Polyols
Glycerol Propylene glycol Polyethylene glycol (PEG)

Organic Esters
Phthalate esters Citrate esters Triacetin

Oils/Glycerides
Castor oil Fractionated Coconut oil Acetylated Monoglycerides 20

CONT

21

Solvent/Vehicles

The key function of a solvent system is to dissolve or disperse the polymers and other additives. The major classes of solvents being used are, Water Alcohols Ketones Esters Chlorinated hydrocarbons

Because of environmental and economic considerations, water is the solvent of choice; however organic coating is totally cannot be avoided
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Colorants/Opacquents
These materials are generally used as ingredients in film-coating formulae to contribute to the visual appeal of the product, but they also improve the product in other ways. Colorants for film coating are having, in more or less amount, property of Opacifiers. So they would give protection to active ingredients in presence of light. Concentration (2.5-8%)

Organic dyes and Inorganic colors their lakes

Sunset yellow Ion oxide red, Black

Natural colors
Carmine

Erythrosine
Tartrazine

Titanium dioxide

Anthrocyanine
Ribofloavine

23

Miscellaneous coating solution components

To provide a dosage form with a single characteristic,

special materials may be incorporated into a solution. Flavors and sweeteners are added to mask unpleasant odors or to develop the desired taste. For example, aspartame, various fruit spirits (organic solvent), water soluble pineapple flavor (aqueous solvent) etc. Surfactants are supplementary to solubilise immiscible or

insoluble ingredients in the coating. For example: Spans,

Tweens etc. 24

CONT

Antioxidants are incorporated to stabilize a dye system to

oxidation and color change. For example: oxides, phenols etc.

Antimicrobials are added to put off microbial growth in the coating composition. Some aqueous cellulosic coating solutions are mainly prone to microbial growth, and longlasting storage of the coating composition should be avoided. For example: alkylisothiazloinone, carbamates,

benzothiazoles etc.

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PROCESS CONTROLS

Pan Variables

Rotating speed of pan

Tablet motion, a factor influenced greatly by pan speed, can be a

major issue in the following cases:

Tablet breakage Edge wear, Surface erosion. The uniformity of distribution of the applied coating i.e. higher the pan speeds being better in this regard.

26

CONT
It is well documented that increasing the rotating speed of the pan improves the mixing of tablets. The pan speed affects the time the tablets spend on the spraying zone and, subsequently, the homogeneous distribution of the coating solution on the surface of each tablet throughout the batch.

Increasing the pan speed decreases the thickness variation and

increase the uniformity of coatings.

Too much rotating speed of the pan will cause the tablet to undergo unnecessary attrition and breakage. 27

Pan loading
Pan loadings are usually defined in terms of volume fill, rather

than by weight. Thus, the optimum pan loading by weight will

vary from product to product, depending on the apparent density of that product.

The difficulty arises for the following reasons:

On the laboratory scale, it is not too difficult to ensure that a pan is

appropriately loaded. Even when only a very small amount of

product is available, this problem can be dealt with by bulking up active tablets with placebos to make a full charge. 28

CONT.

On the production scale, total batch weight of the compressed

tablets, can be divided into a whole number of pan loads. For

example, if the total batch weight is 500kg, and these tablets are to be coated in a pan that optimally holds 120kg per run, then the instructions will call for five pan loads of 100kg each to be coated. The result is that each coating run will have each pan under loaded by about 16%. In the example shown, a 16% under loading may not seem to be too much of a problem, but potentially critical issues

that may arise include:

29

CONT.

When pan is under loaded, the side walls of the coating pan, or

even baffles, become more exposed to the spray, causing

coating liquid to build up on exposed metal surfaces, often with the result that tablets will stick to these surfaces.

This can be minimized by the following ways,

Changing the gun-to-bed distances

Gun spacing
The number of guns used can minimize this problem.

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SPRAY VARIABLES

Gun-to-tablet-bed distance:
With the help of rudimentary positioning tools, such as a ruler, the operator is left to set up gun position. Gun positioning needs to be optimized to: Ensure that optimal and reproducible bed coverage is achieved. Facilitate broad coverage while providing maximum surface drying time.

Achieve reproducible spray droplet characteristics as they

arrive at the tablet surface

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Spray gun dynamics

Quality attributes of film-coated tablets that can be associated with spray-gun performance include; Appearance - Coating gloss - Coating roughness - Existence of defects ("picking," edge chipping/edge wear, filling in of logos) - Colour uniformity Functional - Uniformity of distribution of coating - coating porosity (which influences film permeability) -Solvent (water) penetration into the tablet cores, and hence

product stability.
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Spray rate

The spray rate is a significant parameter since it impacts the moisture content of the formed coating and, subsequently, the quality and uniformity of the film. A low coating liquid spray rate causes incomplete

coalescence of polymer due to insufficient wetting, which

could effect in brittle films. A high coating liquid spray rate may result in over wetting of the tablet surface and subsequent problems such as picking and sticking.

33

CONT

If the spray rate is high and the tablet surface temperature is

low, films are not formed during the spraying but the post
drying phase, and rapid drying often produces cracks in the films.

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PROCESS AIR VARIABLES

Atomizing air pressure

In general, increasing the spraying air pressure decreases the surface roughness of coated tablets and produces denser and thinner films.

If spraying air pressure is excessive, the spray loss is great, the formed droplets are very fine and could spray-dry before

reaching the tablet bed, resulting in inadequate droplet

spreading and coalescence.

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CONT

If spraying air pressure is inadequate, the film thickness and

thickness variation are greater possibly due to change in the

film density and smaller spray loss.

In addition, with low spraying air pressure big droplets could locally over wet the tablet surface and cause tablets to stick to each other.

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Inlet air temperature

The inlet air temperature affects the drying efficiency (i.e.

water evaporation) of the coating pan and the uniformity of

coatings.

High inlet air temperature increases the drying efficiency of the aqueous film coating process and a decrease in the water penetration into the tablet core decreases the core tablet porosity, tensile strength and residual moisture content of

coated tablets.

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CONT

Too much air temperature increases the premature drying of

the spray during application and, subsequently, decreases the

coating efficiency.

Measuring the pan air temperature helps to manage the optimum conditions during the coating process and, consequently, enables predicting possible drying or over wetting problems which may result in poor appearance of the

film or may have unfavorable effects on the moisture and

heat sensitive tablet cores.

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Drying-air volume

Drying-air volume is selected based on,

1. The recommendations of the vendor of the equipment 2. On the basis of the optimum conditions designed for the airhandling system that has been installed.

- The supply and exhaust air fan speeds should be set, based on the equipment used, to meet the negative pressure pan

settings that are usually recommended.

39

CONT
Once the appropriate drying air volume has been established, this setting becomes a driver for other key processing variables, such as spray rate.

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COATING EQUIPMENT

Most commonly used equipments are,

The standard coating pan

The perforated coating pan The Fluidized bed coater

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Conventional Pan System

It consists of a circular metal pan mounted somewhat angularly

on a stand and is rotated on its horizontal axis by a motor.

Heated air is directed into the pan and onto the tablet bed surface , and is exhausted by means of ducts positioned through the front of the pan.

Conventional Coating Pan

Upgraded Conventional Coating Pan

Side Vented Coating Pan 42

43

CONT

A significant improvement in the particle movement & drying

efficiency of the standard coating pan is achieved by the,

Pellegrini pan Immersion sword Immersion tube systems

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IMPROVEMENT IN THE PARTICLE MOVEMENT

Mixing of the core bed is important for a uniform application of

the coating material as well as for effective drying.

The most basic approach to improve the core bed movement in pans rotating on inclined or horizontal axes was to introduce baffles and blades in the pan. One of the first pans with a single baffle was invented by Keil in 1965 The first coating pan rotating on a horizontal axis equipped with tapered side walls and an integral baffle system was introduced by Pellegrini and is well-known as the Pellegrini pan.

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PELEGRINI PAN

The side walls of this pan are shaped with a pronounced taper,

which increases the efficiency of particle movement by forcing the

cores into an additional lateral movement. This results in a composite core movement yielding improved exposure of the core to the coating material.

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CONT

USING BAFFLES AND BLADES INCREASES RISK of

friction between the core material and the pans, potentially
resulting in increased amounts of dust formed during the coating process. Hence, FOCUS was on the IMPLEMENTATION OF

PERFORATED PANS to improve the air transport in the core bed and consequently to increase the mixing and drying efficiency.

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IMPLEMENTATION OF PERFORATED PANS

Hostetler, for instance, has modified the peripheral wall with
perforations and positioned an air supplying inlet at the lower peripheral area, forming the so-called side-vented pan. The shape of the pan, the perforations in the peripheral wall, and the side positioned air supplying inlet were not only intended to increase core movement and air transfer, but also to increase the contact area of the cores with the coating material.

Side-vented pan of Hostetler

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IMPROVEMENT IN THE DRYING EFFICIENCY

Generally, the energy required for evaporating the

moisture

from the coating layers is derived from the drying air.

The duration of the coating process as well as the quality of the end product thus crucially depend on the efficiency of heat and mass transfer. Increasing the heat and mass transfer either directly (for example by increasing temperature and rotation speed or implementation of perforations) or indirectly by improving the drying air supply can improve drying efficiency.

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CONT.

With the conventional drying method, the drying air is blown

across the surface of the core bed. As only the surface of the core
bed is exposed to the drying air, insufficient drying of core materials and impaired spraying processes might occur. Hence, different drying gadgets have been developed, of which the two conventional ones are the immersion tube and the immersion sword.

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IMMERSION SWORD SYSTEM

With the immersion sword system, drying air is introduced

through a perforated metal sword device that is immersed in the

tablet bed. The drying air flows upward from the sword through the bed. Since the air is more intimately mixed with the wetted tablets, a more efficient drying environment is provided. As shown in figure.

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CONT

Immersion Sword system 52

IMMERSION TUBE SYSTEM

In this type of system the immersed tube delivers the heated air, and a spray nozzle is built in the tip of the tube. During this operation , the coating solution is applied simultaneously with the heated air from the immersed tube . The drying air flows upward through the tablet bed and is exhausted by a conventional duct.

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CONT

Both the immersion sword and immersion tube systems are

adaptable to conventional coating pans.

Relatively rapid processing times have been reported for both film and sugar coating with this system.

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Pan Coaters Rotating on Vertical Axis

Represents another approach towards the improvement of pan

coating.
Designed to overcome the problem of mechanical abrasion of cores encountered in horizontally rotating pans with baffles or blades. Generally, in coaters that rotate around vertical axes, the feed material to be coated is placed in a container which is moved by a driving motor. This causes the circulation of particles on the axis of rotation.

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CONT.
The centrifugal force first pushes the particles outwards from the centre to the pan wall and then upwards following the curve of the wall. Particles then drop down back into the middle of the container due to gravity. Usually, such equipments include a return device at the upper part of the wall which assists the feed material to roll back into the container.

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PERFORATED PAN SYSTEM

In Accela-cota and Hi-coater systems, drying air is directed into

the drum, is then passed through the tablet bed, and is exhausted
through perforation in the drum.

Accela-cota 57

Hi-coater

Stretched" Design Provides Shorter Process Times

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CONT
An increased spray zone is accomplished by lengthening the coating pan while maintaining the same diameter

CONT

59

CONT.

The most effective method to increase spray rates for any tablet

coating process is to increase the number of spray guns within

the coating pan.

The Stretched coating pan can incorporate as many as ten spray guns doubling the amount of spray guns in a typical batch coating system. The Stretched design also minimizes tablet attrition by reducing the tablet bed depth when

compared to a similar batch size in a larger pan diameter.

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CONT
Manifold Spray Bar Provides Cleaning Advantages
manifold spray bar eliminates the external nozzle air and solution lines on the exterior of the spray bar. Instead, nozzle air and solution is delivered within the interior of the spray bar.

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CONT
one-gasket design allows for quick assembly of the spray bar.

Changing the number of spray guns has never been easier.

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CONT
Fully Perforated or Integrated Plenum

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Driacoater

The Driacoater introduces drying air through hollow perforated ribs located on inside periphery of the drum. As coating pan rotates the ribs dip into the tablet bed, and dying air passes through and fluidizes the tablet bed. Air is exhausted from back of the pan.

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CONT.

For hard sugar coating, DRIACOATERS with perforated multisided drums are used. The machines are capable to handle

sugar and sugar free solutions, (Sorbitol, Xylitol, Malitol, Isomalt, etc.), glazing and polishing solutions as well as aqueous suspensions. Automatic loading and unloading, inside pan cleaning and fully automatic process capabilities characterize this DRIACOATER with batch sizes from 625 ltr to 3750 ltr.
Complete production units including: Dosing and spraying systems for solutions, flavor and polishing Dosing/distribution for solid powdery materials Supply and exhaust air installations with air conditioning

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FLUIDIZED BED SYSTEM

Process advantages
Uniform, continuous product coating. Aqueous or organic coatings can be applied. Coating and drying take place in one machine. In terms of Total Containment, the coating process and the filling

and emptying of the machine can be carried out in complete

isolation and without product spreading into the environment. When using organic solvents, the process machines can also be made inert and used with a solvent recovery system.

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CONT

Principle of operation
With fluid bed coating, particles are fluidized and the coating
fluid sprayed on and dried. Small droplets and a low viscosity of the spray medium ensure an even product coating.

Glatt offers Batch Fluid Bed Systems in different batch sizes with: Top Spray Coating Bottom Spray Coating (Wurster Coating) Tangential Spray Coating (Rotor Pellet Coating)

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CONT

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CONT
Top Spray Coating
This process is used for general coatings right up to enteric coating. With top spray coating in the fluid bed (batch and continuous), particles are fluidized in the flow of heated air, which is introduced into the product container via a base plate. .

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CONT
The coating liquid is sprayed into the fluid bed from above against the air flow (countercurrent) by means of a nozzle. Drying takes place as the particles continue to move upwards in the air flow. Small droplets and a low viscosity of the spray medium ensure that the distribution is uniform. Coating in the continuous fluid bed is particularly suitable for protective coatings/colour coatings where the product throughput rates are high. The product is continuously fed into one side of the machine and is transported onwards via the sieve bottom by means of the air flow. Depending on the application, the system is sub-divided into pre-heating zones, spray zones and drying zones. The dry, coated particles are continuously extracted. 70

CONT.
Bottom Spray Coating (Continuous fluid bed) Particularly suitable for protective coatings/colour coatings
where the product throughput rates are high. The product is continuously fed into one side of the machine and is transported onwards via the sieve bottom by means of the air flow.

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CONT.
Depending on the application, the system is sub-divided into preheating zones, spray zones and drying zones whereby spraying can take place from below in the form of a bottom spray. The dry, coated particles are continuously extracted.

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CONT.
Tangential Spray Coating (Rotor pellet coating)
Ideal for coatings with high solid content. The product is set into a spiral motion by means of a rotating base plate, which has air fed into the powder bed at its edge. The spray nozzle is arranged tangentially to the rotor disc and also sprays concurrently into the powder bed. Very thick film layers can be applied by means of the rotor

method.

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Spouted Bed Coaters

An effective alternative to fluidized beds for handling

coarse particles over 2 mm diameter.

Main parts of spouted bed equipment can be defined as,

Air/gas inlet chamber Opening device

Process chamber
Spraying system Exhaust chamber. 74

CONT

Main parts of a spouted bed equipment with different processing systems

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CONT
The air/gas inlet chamber comprises the lower part of the apparatus and - like in the fluidized bed system can be implemented in single or divided form. Unlike the fluidized bed processes, the spouting air/gas does not enter the processing chamber through the air distribution base plate, but through an opening device with relatively high velocities, typically between 1 and 30 m/s. The opening device can be constructed as a central orifice or a longitudinal slot at the bottom. The process chamber is usually cylindrical with a conical base, in the centre of which the opening device is installed. In general, the spraying system and the exhaust chamber are similar to those of fluidized bed systems. 76

Enteric Film Coatings

By definition, enteric coatings are those which remain intact in the stomach (and exhibit low permeability to gastric fluids). but break down readily. once the dosage form reaches the small intestine. The prime uses of such coatings are:

To maintain the activity of drugs that are unstable when exposed to the gastric milieu (e. g., erythromycin and pancreatin).
To minimize either nausea or bleeding that occurs with those drugs that irritate the gastric mucosa (e.g. aspirin and certainsteroids).
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PELLETISATION
Pelletisation is an agglomeration process that converts fine powder blend of drugs and excipients into small, free flowing, spherical units, referred to as pellets.

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WHY PELLETS ?

Excellent Stability Dust free round pellets Easy to dose Compact structure Very low hygroscopicity High bulk density Dense, Uniform surface Narrow grain size distribution Low abrasion High active ingredient content possible Controlled release application

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PREPARATION OF PELLETS

Drum/pan pelletization

Extrusion- spheronization
Centrifugal drug-layering Fluidized-bed pelletization High-shear melt pelletization

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Extrusion-spheronization

Pelletization by forming and spheronizing extrudates Features: Continuous process Fast process Easy to up-scale Stand alone units but also fully integrated systems available Very high drug loads possible due to special extruder design Integration with up-and downstream equipment possible. Applications Forming of pellets between 0.5 and 3 mm diameter.

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POWDER LAYERING PROCESS (ROTO SYSTEM)

PRINCIPLE OF OPERATION
With fluid bed coating, particles are fluidized and the coating/ Binder fluid sprayed on and dried. Small droplets and a low viscosity of the spray medium ensure an even product coating.

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Liquid layering of pellets

A starting grain or a pellet can be presented as the starting material. The pellet is built up to the required grain size by adding the layering substance one layer at a time. Powder and binders, suspensions or solutions make suitable layering substances. Thick layers can be applied to the starting grains, which, in the case of layers containing active ingredients, allow large amounts of active ingredient to be incorporated

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Melt granulation pelletization

The active and binder powders are mixed and heated to a temperature above the melting point of the binder. Granulation and pelletization are then carried out in a single operation. Features:
Very fast process True One-Pot operation Special polymer liners to minimize sticking For melting a heated jacket or optional 'microwave energy' can be used

Applications Forming of pellets between 0.5 and 2 mm diameter. By selection of the binder material it is possible to form sustained release forms without additional coating.

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CONCLUSION
In recent decades, coating of pharmaceutical dosage forms has been subject of remarkable developmental efforts aiming to ensure and enhance end product quality.
Improvements regarding particle movement, heat and energy transfer, film distribution, drying efficiency and continuous processing have contributed to significantly develop this technology. However, evaluation and success of further constructional improvements in coating methods appear to depend on accurate analytical tools and advanced methods for process modeling and control. In this regard, achieving optimal manufacturing efficiency and high end product quality still remains a key challenge for future research efforts. 85

POLYMERS USED IN FILM COATING

POLYMERS FOR MODIFIED RELEASE APPLICATION Methacrylate Ester Copolymers Ethyl cellulose (EC)

CONVENTIONAL COATING POLYMERS

ENTERIC POLYMERS Cellulose acetate phthalate (CAP) Polyvinyl Acetate Phthalate (PVAP) Shellac Methacrylic Acid Copolymers Cellulose Acetate Trimellitate (CAT) Hydroxypropyl methylcellulose phthalate (HPMCP)

Cellulose ethers HPMC (Hypromellose, Pharmacoat) Methylcellulose (MC) Hydroxyethyl cellulose (HEC) Hydroxypropyl cellulose (HPC) Acrylic polymers Methacrylate Amino Ester Copolymer

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CONVENTIONAL COATING POLYMERS CELLULOSE ETHERS

The structure of cellulose permits three hydroxyl groups per repeating anhydro-glucose unit to be replaced.

If all three hydroxyl groups are replaced the degree of

substitution (DS) is designated as 3, and so on for lower degrees of substitution. The term molar substitution (MS) covers the situation where a side chain carries hydroxyl groups capable of substitution and takes into account the total moles of a group whether on the backbone or side chain.

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CONT
Both DS and MS profoundly affect the polymer properties with respect to solubility and thermal gel point. The polymer chain length, together with the size and extent of branching, will of course determine the viscosity of the polymer solution. As a generality, film coating demands polymers at the lower end of the viscosity scale. It is soluble in both aqueous media and the organic solvent systems normally used for film coating

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CELLULOSE ETHERS (HPMC) (Hypromellose, Pharmacoat)

Provides aqueously soluble films which can be colored by the use of pigments or used in the absence of pigments to form clear films. Non-tacky

Typical low-viscosity polymer can be sprayed from an aqueous

solution containing around 1015%w/w polymer solids

89

(HPMC) (Hypromellose, Pharmacoat) Cont..

Advantages:

It does not affect tablet disintegration and drug availability,

It is cheap, flexible, and highly resistant to heat, light and moisture, it has no taste and odor, color and other additives can be easily incorporated. Disadvantage: When it is used alone, the polymer has tendency to bridge or fill the debossed tablet surfaces. So mixture of HPMC and other polymers/ plasticizers is used

90

Different available grades of HPMC

Available in a number of viscosity designations defined as the

nominal viscosity of a 2%w/w aqueous solution at 20C.

Thus a 5mPa s grade will have a nominal viscosity of 5 mPa-s in 2% aqueous solution in water at 20C and similarly with 6 mPa-s, 15 mPa-s and 50 mPa-s grades.

Commercial nomenclature for these grades may still describe them as 5 cP.
91

 Commercial designations such as E5 (Methocel) or 606

(Pharmacoat) also correspond with the viscosity designation,

such that for example Methocel E5 has a nominal viscosity of 5mPa s under the previously described standard conditions. While Pharmacoat 606 would have a nominal viscosity of 6 mPa s under the same conditions. The first two digits of the four-digit designation specify the nominal percentage of methoxyl groups while the final two

specify the nominal percentage of hydroxypropoxyl groups.

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93

PHARMACOAT

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PHARMACOAT Cont.

PHARMACOAT

film

has

the

hardness

and

strength

characteristic of cellulose derivatives.

Although PHARMACOAT film is not brittle, as acrylic polymers, addition of a plasticizer such as polyethylene glycol (PEG 6,000) is effective when highly flexible film is required. Moreover, addition of a water-insoluble polymer such as Ethylcellulose (EC) or Hydroxypropyl methylcellulose phthalate (HPMCP) to PHARMACOAT delays dissolution of the film, which is useful for the masking of bitter taste or unacceptable texture, as well as delaying drug dissolution.

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SOLUBILITY OF MIXED FILM IN SIMULATED GASTRIC FLUID AND SIMULATED

96

Methylcellulose (MC) Substituent group: CH3

This polymer is used rarely in film coating possibly because of

the lack of commercial availability of low viscosity material

meeting the appropriate compendial requirements.

It is not frequently used as HPMC because soluble in fewer organic solvents.

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DIFFERENT AVAILABLE GRADES

98

Hydroxyethyl cellulose (HEC) Substituent group: CH (OH)CH3

This water-soluble cellulose ether is generally insoluble in

organic solvents.
The USNF is the sole pharmacopoeial specification; there is no requirement on the quantity of hydroxyethyl groups to be present. The USNF allows the presence of additives to promote dispersion of the powder in water and to prevent caking on

storage.

99

Hydroxypropyl cellulose (HPC) Substituent group: CH2 CH (OH)CH3

HPC has the property of being soluble in aqueous below 40oc

(insoluble above 45 C), gastric fluid and many polar organic

solvents.

Its films unfortunately tend to be rather tacky, which possess restraints on rapid coating; HPC films also suffer from being weak.

Currently this polymer is very often used in combination with other polymers to provide additional adhesion to the substrate. 100

Hydroxypropyl cellulose (HPC) Cont.

The EB/BP has no requirements on hydroxypropoxyl content.

The USNF states this must be less than 80.5% while the JP has
two monographs differing in substitution requirements. The monograph most closely corresponding to the USNF material has a substitution specification of 53.477.5%.

101

ACRYLIC POLYMERS Methacrylate Amino Ester Copolymer

This polymer is basically insoluble in water but dissolves in acidic media below pH 4. In neutral or alkaline environments, its films achieve solubility by swelling and increased permeability to aqueous media. Talc, magnesium stearate or similar materials are useful additions to the coating formula as they assist in decreasing the sticky or tacky nature of the polymer. In general, the polymer does not require the addition of a plasticizer. 102

POLYMERS FOR MODIFIED RELEASE APPLICATION Methacrylate Ester Copolymers

These materials are insoluble over the entire physiological pH

range. However they do possess the ability to swell and

become permeable to water and dissolved substances so that they find application in the coating of modified release dosage forms. The two polymers Eudragit RS and RL can be mixed and blended to achieve a desired release profile. The addition of hydrophilic materials such as the soluble cellulose ethers,

polyethylene glycol (PEG), etc., will also enable modifications to

be achieved with the final formulation.

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 The polymer Eudragit RL is strongly permeable and thus only

slightly retardant. Its films are therefore also indicated for use in
quickly disintegrating coatings

For aqueous spraying a latex form of each polymer is available. In addition the polymer Eudragit NE30D has been made for this purpose. This material is also used as an immediate-release nonfunctional

coating in film coat formulations where relatively large quantities

of water-soluble materials are added to ensure efficient disruption of the coat. 104

Ethyl cellulose (EC) Substituent groupCH2CH3

It possesses good solubility in common solvents used for film

coating.

Apart from its extensive use in controlled release coatings, ethyl cellulose has found a use in organic solvent-based coatings in a mixture with other cellulosic polymers, notably HPMC.

Ethyl cellulose also conveys additional gloss and shine to the tablet surface.

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 In many ways ethyl cellulose is an ideal polymer for modified

release coatings.
It is odorless, tasteless and it exhibits a high degree of stability not only under physiological conditions but also under normal storage conditions, being stable to light and heat at least up to its softening point of c. 135c

Only the USNF contains a monograph, an ethoxy group content of between 44.0 and 51.0% is specified.

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 The USNF also contains a monograph Ethyl cellulose Aqueous

Dispersion which defines one type of such material which finds

a use in aqueous processing. The monograph permits the presence of cetyl alcohol and sodium lauryl sulphate which are necessary to stabilize the dispersion.

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ENTERIC POLYMERS Cellulose acetate phthalate (CAP)

Enteric polymers are designed to resist the acidic nature of the

stomach contents, yet dissolve readily in the duodenum.

Of the generally accepted solvents used for tablet coating, CAP is insoluble in water, alcohols and chlorinated hydrocarbons

A pseudo latex version of CAP is available (Aquateric) as a dry powder for reconstitution in water and offers the convenience of aqueous-based processing

.
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 CAP is a white free-flowing powder usually with a slightly

odor of acetic acid.

The JP has requirements for the content of acetyl and phthalyl to be respectively 1722 and 3040% while the USNF requires 21.526 and 3036% respectively. CAP is somewhat prone to hydrolysis. Aquacoat CPD Sepifilm LP Klucel Aquacoat ECD Metolose Enteric Coatings Taste masking Sustained release coating Sub coat moisture and barrier sealant pellet coating 109

Polyvinyl Acetate Phthalate (PVAP)

Polyvinyl acetate phthalate possesses the following solubility

characteristics, with the extent of solubility given in parentheses:

methanol (50%) methanol/methylene chloride (30%) ethanol 95% (25%) ethanol/water 85:15 (30%) An aqueous dispersible form (Sureteric) is available for waterbased spraying.

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Shellac

Shellac is insoluble in water but shows solubility in aqueous

alkalis; it is moderately soluble in warm ethanol.

Shellac suffers from the general drawback that it is a material of natural origin and consequently suffers from occasional supply problems and quality variation

EmCoat 120 N Marcoat 125

Enteric Coatings Taste/Odor Masking

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Methacrylic Acid Copolymers

Because these polymers possess free carboxylic acid groups they

find use as enteric-coating materials, forming salts with alkalis

and having an appreciable solubility at pH in excess of 5.5.

Of the two organic solvent soluble polymers, Eudragit S100 has a lower degree of substitution with carboxyl groups and consequently dissolves at higher pH than Eudragit L100. Used in combination, these materials are capable of providing films with a useful range of pH over which solubility will occur.

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 Polyethylene glycols are frequently added as they provide a

measure of gloss to the final product. They also assist in

stabilizing the water-dispersible form, Eudragit L30D

Both Eudragit L100 and S100 are available in powder form and for convenience purposes they are also available as concentrates in organic solvent solution, which are capable of further dilution in the common processing solvents used in organic solvent-

based film coating.

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Cellulose Acetate Trimellitate (CAT) Substituent Groups (COCH3, COC6H3 (COOH) 2

The useful property of this polymer is its ability to start to

dissolve at the relatively low pH of 5.5, which would help

ensure efficient dissolution of the coated dosage form in the upper small intestine. Chemically this polymer bears a strong resemblance to cellulose acetate phthalate but possesses an additional carboxylic acid group on the aromatic ring. Typical values for timellityl and acetyl percentages are 29 and 22% respectively

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Hydroxypropyl methylcellulose phthalate (HPMCP)

HPMCP is insoluble in water but soluble in aqueous alkalis

and acetone/water 95:5 mixtures.

The degree of substitution of the three possible substituents determines the polymer characteristics, in particular the pH of dissolution. HPMCP may be plasticized with diethyl phthalate, acetylated monoglyceride or triacetin. Mechanically it is a more flexible polymer and on a weight basis will not require as much plasticizer as CAP or CAT.

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 HPMCP is a white powder or granular material. USNF and JP

describe two substitution types, namely HPMCP 200731 and

220824. The six digit nomenclature refers to the percentages of the respective Substituent methoxyl, hydroxypropoxyl and carboxy-benzoyl groups. For example, HPMCP 200731 has a nominal methoxyl content of 20% and so on for the other two substituents. Fine particle size grades designated with a suffix F are intended for suspension in aqueous systems, with suitable plasticizers prior to spray application.

116

 Commercial designations such as 50 or 55 refer to the pH (10)

of the aqueous buffer solubility.

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TRUE LATEXES

These are very fine dispersions of polymer in an aqueous phase and particle size is crucial in the stability and use of these materials. They are characterized by a particle size range of between 10 and 1000 nm.

At the other end of the size range the characteristic of colloidal particles is approached where such dispersions are barely opaque to light and are almost clear.
One of the chief ways of producing latex dispersions is by emulsion polymerization. The reaction is quenched when the particle size is in the range 50200 nm. Using this process the following acrylate polymers are produced: Eudragit L10055 and NE30D. 118

PSEUDO LATEXES
Commercially there are two main products which fall into this category, both of them utilize ethyl cellulose as the film former but are manufactured in quite a different way and their method of application also differs significantly. Characteristically pseudo latexes are manufactured starting with the polymer itself and not the monomer. By a physical process the polymer particle size is reduced thereby producing dispersion in water; the characteristics of this dispersion need not differ significantly from true latex, including particle size considerations. The pseudo latex is also free of monomer residue and traces of initiator, etc. Aqueous dispersions have significant advantages, enabling processing of water-insoluble polymers from an aqueous media. 119

CONT..
Mechanism Minimum film-forming temperature (MFT) this is the minimum temperature above which film formation will take place using individual defined conditions. It is largely dependent on the glass transition temperature (Tg) of the polymer. With aqueous dispersions Lehmann recommends to keep the coating temperature 1020C above the MFT to ensure that optimal conditions for film formation are achieved.

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COATING DEFECTS

Picking and sticking: This is when the coating removes a piece of

the tablet from the core.

Caused by over-wetting the tablets, by under-drying, or by poor tablet quality. Solution A reduction in the liquid application rate Increase in drying air temperature or air volume Bridging: This occurs when the coating fills in the lettering or logo on the tablet.
.

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 Is typically caused by , improper application of the solution, poor design of the tablet embossing, high coating viscosity, high percentage of solids in the solution, or improper atomization pressure Increasing the plasticizer content or changing the plasticizer can solve this problem.

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Capping: This is when the tablet separates in laminar fashion.

The problem stems from

improper tablet compression How you operate the coating system, however, can

exacerbate the Problem

over-dry the tablets in the preheating stage. That can make the tablets brittle and promote capping. Erosion: This can be the result of soft tablets, an over-wetted tablet surface, Inadequate drying or lack of tablet surface strength.

123

Peeling and frosting: This is a defect where the coating peels away

from the tablet surface in a sheet

This could be due to a defect in the , coating solution, over-wetting or high moisture content in the tablet core

Chipping: This is the result of high pan speed, a friable tablet core, or a coating solution that lacks a good plasticizer. 124

Mottled color: This can happen when the ,

coating solution is improperly prepared

the actual spray rate differs from the target rate the tablet cores are cold, or the drying rate is out of spec.

Use of lake dye may eliminate the problem.

Orange peel: This refers to a coating texture that resembles the surface of an orange. It is usually the result of high atomization pressure in combination with spray rates that are too high. Thinning the solution with additional solvent can solve the problem 125

 Twinning: This is the term for two tablets that stick together,

and its a common problem with capsule shaped tablets.

We can solve this problem by balancing the pan speed and spray rate. Try reducing the spray rate or increasing the pan speed.

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EVALUATION OF COATING SYSTEMS

Evaluating coating systems requires evaluation of both the

coatings and the coated tablets.

Physical characterization of the coating system should include particle size, preparation time and viscosity because each affects the handling and use of the powdered on step coating systems. Large particles minimizes dust and short process time have obvious advantages. Low viscosity enables to create a coating with high ration of solids, which leads to faster tablet coating.

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Once coated tablet should be evaluated for the,

Gloss
Opacity Color uniformity

Disintegration
Adhesion time Logo bridging Film strength and flexibility Edge wear

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