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Next Page: Problems in tablet manufacturingPrevious Page: Tablet Manufacturing methods
2 Aspects of tablet coating
3 Basic principle of tablet coating
4 Type of tablet coating process
4.1 Sugar coating
4.1.1 Sealing/Water proofing
4.1.3 Grossing/ smoothing
4.1.4 Colour coating
4.2 Film Coating
4.2.1 Process description
4.2.2 Process details
4.2.3 Basic process requirements for film coating
4.2.4 Coating formula optimization
4.2.5 Materials used in film coating
4.3 Enteric coating
4.3.1 = Enteric sugar coating
4.3.2 Enteric film coating
4.3.3 Controlled release coating
4.4 Specialized coating
4.4.1 Compressed coating
4.4.2 Electrostatic coating
4.4.3 Dip coating
4.4.4 Vacuum film coating
6 Process parameters
6.1 Air capacity
6.2 Coating composition
6.3 Tablet surface area
6.4 Equipment efficiency
7 Key Phrases
Coated tablets are defined as “tablets covered with one or more layers of mixture of various substances such as natural or synthetic resins ,gums ,inactive and insoluble filler, sugar, plasticizer, polyhydric alcohol ,waxes ,authorized colouring material and some times flavoring material .
Coating may also contain active ingredient. Substances used for coating are usually applied as solution or suspension under conditions where vehicle evaporates.
Aspects of tablet coating
i) Avoid irritation of oesophagus and stomach
ii) Avoid bad taste
iii) Avoid inactivation of drug in the stomach
iv) Improve drug effectiveness
v) Prolong dosing interval
vi) Improve dosing interval
vii) Improve patient compliance
i) Reduce influence of moisture
ii) Avoid dust formation
iii) Reduce influence of atmosphere
iv) Improve drug stability
v) Prolong shelve life
i) Avoid bad taste
ii) Improve product identity
iii) Improve appearance and acceptability
Basic principle of tablet coating
The principle of tablet coating is relatively simple. Tablet coating is the application of coating composition to moving bed of tablets with concurrent use of heated air to facilitate evaporation of solvent.
Basic principles involve
i) Insulation which influences the release pattern as little as possible and does not markedly change the appearance.
ii) Modified release with specific requirement and release mechanism adapted to body function in the digestive tract.
iii) Colour coating which provides insulation or is combined with modified release coating.
Type of tablet coating process
Compressed tablets may be coated with coloured or uncoloured sugar layer. The coating is water soluble and quickly dissolves after swallowing. The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or order. The sugar coat also enhances the appearance of the compressed tablet and permit imprinting manufacturing’s information. Sugar coating provides a combination of insulation, taste masking, smoothing the tablet core, colouring and modified release. The disadvantages of sugar coating are the time and expertise required in the coating process and thus increases size, weight and shipping costs.
Sugar coating process involves five separate operations:
I. Sealing/Water proofing: provides a moisture barrier and harden the tablet surface.
II. Subcoating: causes a rapid buildup to round off the tablet edges.
III. Grossing/Smoothing: smoothes out the subcoated surface and increases the tablet size to predetermine dimension.
IV. Colouring: gives the tablet its colour and finished size.
V. Polishing: produces the characteristics gloss.
Prior to applying any sugar/water syrup, the tablet cores must be sealed, thoroughly dried and free of all residual solvents.
The seal coat provides a moisture barrier and hardness the surface of the tablet in order to minimize attritional effects. Core tablets having very rapid disintegration rates conceivably could start the disintegration process during the initial phase of sugar coating. The sealants are generally water-insoluble polymers/film formers applied from an organic solvent solution. The quantities of material applied as a sealing coat will depend primarily on the tablet porosity, since highly porous tablets will tend to soak up the first application of solution, thus preventing it from spreading uniformly across the surface of every tablet in the batch. Hence, one or more further application of resin solution may be required to ensure that the tablet cores are sealed effectively.
Common materials used as a sealant include Shellac, Zine, Cellulose acetate phthalate (CAP), Polyvinylacetate phthalate, Hyroxylpropylcellulose, Hyroxypropylmethylcellulose etc.
Subcoating is the actual start of the sugar coating process and provides the rapid buildup necessary to round up the tablet edge. It also acts as the foundation for the smoothing and colour coats.
Generally two methods are used for subcoating:
i)The application of gum based solution followed by dusting with powder and then drying. This routine is repeated until the desired shape is achieved.
ii)The application of a suspension of dry powder in gum/sucrose solution followed by drying.
Thus subcoating is a sandwich of alternate layer of gum and powder. It is necessary to remove the bulk o the water after each application of coating syrup.
TABLE.23. TYPICAL BINDER SOLUTION FORMULATION FOR SUBCOATING(1)
Gum acacia (powdered)
TABLE.24. TYPICAL DUSTING POWDER FORMULATION FOR SUBCOATING(1)
Talc, asbestos free
Sucrose( powdered )
Gum acacia (powdered)
TABLE.25. TYPICAL SUSPENSION SUBCOATING FORMULATION(1)
Talc, asbestos free
The grossing/smoothing process is specifically for smoothing and filing the irregularity on the surface generated during subcoating. It also increases the tablet size to a predetermined dimension.
If the subcoating is rough with high amount of irregularities then the use of grossing syrup containing suspended solids will provide more rapid buildup and better filling qualities. Smoothing usually can be accomplished by the application of a simple syrup solution (approximately 60-70 % sugar solid). This syrup generally contains pigments, starch, gelatin, acacia or opacifier if required.
Small quantities of colour suspension can be applied to impart a tint of the desired colour when there are irregularities in coating.
This stage is often critical in the successful completion of a sugar coating process and involves the multiple application of syrup solution (60-70 % sugar solid) containing the requisite colouring matter. Mainly soluble dyes were used in the sugar coating to achieve the desired colour, since the soluble dye will migrate to the surface during drying. But now a days the insoluble certified lakes have virtually replaced the soluble dyes in pharmaceutical tablet coating. The most efficient process for colour coating involves the use of a predispersed opacified lake suspension.
Sugar-coated tablets needs to be polished to achieve a final elegance. Polishing is achieved by applying the mixture of waxes like beeswax, carnubawax, candelila wax or hard paraffin wax to tablets in polishing pan.
Film coating is more favored over sugar coating.
TABLE.26. COMPARISON BETWEEN FILM COATING AND SUGAR COATING(1)
Weight increase because of coating material
Logo or ‘break lines’
Retain contour of original core. Usually not as shiny as sugar coat type
Rounded with high degree of polish
Operator training required
Adaptability to GMP
Process tends itself to automation and easy training of operator
Usually single stage
Easily adaptable for controlled release
Difficulty may arise
Not usually possible apart from enteric coating
Film coating is deposition of a thin film of polymer surrounding the tablet core. Conventional pan equipments may be used but now a day’s more sophisticated equipments are employed to have a high degree of automation and coating time. The polymer is solubilized into solvent. Other additives like plasticizers and pigments are added. Resulting solution is sprayed onto a rotated tablet bed. The drying conditions cause removal of the solvent, giving thin deposition of coating material around each tablet core.
Usually spray process is employed in preparation of film coated tablets. Accela cota is the prototype of perforated cylindrical drum providing high drying air capacity. Fluidized bed equipment has made considerable impact where tablets are moving in a stream of air passing through the perforated bottom of a cylindrical column. With a smaller cylindrical insert, the stream of cores is rising in the center of the device together with a spray mist applied in the middle of the bottom. For fluidized bed coating, very hard tablets (hardness > 20 N) have to be used.
Basic process requirements for film coating
The fundamental requirements are independent of the actual type of equipments being used and include adequate means of atomizing the spray liquid for application to the tablet core, adequate mixing and agitation of tablet bed, sufficient heat input in the form of drying air to provide the latent heat of evaporation of the solvent. This is particularly important with aqueous-based spraying and good exhaust facilities to remove dust and solvent laden air.
Development of film coating formulations (1)
If the following questions are answered concomitantly then one can go for film coating:
i) Is it necessary to mask objectionable taste, colour and odor?
ii) Is it necessary to control drug release?
iii) What tablets size, shape, or colour constrains must be placed on the developmental work?
Colour, shape and size of final coated tablet are important for marketing and these properties have a significant influence on the marketing strategies. An experienced formulator usually takes the pragmatic approach and develops a coating formulations modification of one that has performed well in the past. Spraying or casting films can preliminarily screen film formulations. Cast films cab is prepared by spreading the coating composition on teflon, glass or aluminum foil surface using a spreading bar to get a uniform film thickness. Sprayed films can be obtained by mounting a plastic-coated surface in a spray hood or coating pan.
Coating formula optimization
Basic formula is obtained from past experience or from various sources in the literature. Modifications are required to improve adhesion of the coating to the core, to decrease bridging of installations, to increase coating hardness, etc. Usually concentration of colorant and opaquant are fixed to get predetermined shade. Common modification is to alter polymer-to-plasticizer ratio or addition of different plasticizer/ polymer. Experimentation of this type can be best achieved by fractional factorial study.
Materials used in film coating
I.Film formers, which may be enteric or nonenteric
VI. Miscellaneous coating solution components
I.Film formers (1)
Ideal requirements of film coating materials are summarized below:
i) Solubility in solvent of choice for coating preparation
ii) Solubility requirement for the intended use e.g. free water-solubility, slow water-solubility or pH -dependent solubility
iii) Capacity to produce an elegant looking product
iv) High stability against heat, light, moisture, air and the substrate being coated
v) No inherent colour, taste or odor
vi) High compatibility with other coating solution additives
vii) Nontoxic with no pharmacological activity
viii) High resistance to cracking
ix) Film former should not give bridging or filling of the debossed tablet
x) Compatible to printing procedure
Commonly used film formers are as follow
i.Hydroxy Propyl Methyl Cellulose (HPMC)
It is available in different viscosity grades. It is a polymer of choice for air suspension and pan spray coating systems because of solubility characteristic in gastric fluid, organic and aqueous solvent system. Advantages include: it does not affect tablet disintegration and drug availability, it is cheap, flexible, highly resistant to heat, light and moisture, it has no taste and odor, colour and other additives can be easily incorporated.
Disadvantage includes: 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.
ii.Methyl Hydroxy Ethyl Cellulose (MHEC)
It is available in wide variety of viscosity grades. It is not frequently used as HPMC because soluble in fewer organic solvents.
iii. Ethyl Cellulose (EC)
Depending on the degree of ethoxy substitution, different viscosity grades are available. It is completely insoluble in water and gastric fluids. Hence it is used in combination with water-soluble additives like HPMC and not alone. Unplasticized ethyl cellulose films are brittle and require film modifiers to obtain an acceptable film formulation. Aqua coat is aqueous polymeric dispersion utilizing ethyl cellulose. These pseudolatex systems contain high solids, low viscosity compositions that have coating properties quite different from regular ethyl cellulose solution.
iv.Hydroxy Propyl Cellulose (HPC)
It is soluble in water below 40oc (insoluble above 45 oC), gastric fluid and many polar organic solvents. HPC is extremely tacky as it dries from solution system. It is used for sub coat and not for colour or glass coat. It gives very flexible film.
Degree of polymerization decides molecular weight of material. It is available in four viscosity grades i.e. K-15, K-30, K-60 and K-90. Average molecular weight of these grades is 10000, 40000, 160000 and 360000 respectively. K-30 is widely used as tablet binder and in tablet coating. It has excellent solubility in wide variety of organic solvents, water, gastric and intestinal fluids. Povidone can be cross-linked with other materials to produce films with enteric properties. It is used to improve dispersion of colourants in coating solution.
vi. Sodium carboxy methyl cellulose
It is available in medium, high and extra high viscosity grades. It is easily dispersed in water to form colloidal solutions but it is insoluble in most organic solvents and hence not a material of choice for coating solution based on organic solvents. Films prepared by it are brittle but adhere well to tablets. Partially dried films of are tacky. So coating compositions must be modified with additives.
viii. Polyethylene glycols (PEG)
Lower molecular weights PEG (200-600) are liquid at room temperature and are used as plasticizers. High molecular weights PEG (900-8000series) are white, waxy solids at room temperature. Combination of PEG waxes with CAP gives films that are soluble in gastric fluids.
ix. Acrylate polymers
It is marketed under the name of Eudragit. EudragitE is cationic co-polymer. Only EudragitE is freely soluble in gastric fluid up to pH 5 and expandable and permeable above pH 5. This material is available as organic solution (12.5% in isopropanol/acetone), solid material or 30% aqueous dispersion. EudragitRL & RS are co-polymers with low content of quaternary ammonium groups. These are available only as organic solutions and solid materials. They produce films for delayed action (pH dependent).
Solvents are used to dissolve or disperse the polymers and other additives and convey them to substrate surface.
Ideal requirement are summarized below:
i) Should be either dissolve/disperse polymer system
ii) Should easily disperse other additives into solvent system
iii) Small concentration of polymers (2-10%) should not in an extremely viscous solution system creating processing problems
iv) Should be colourless, tasteless, odorless, inexpensive, inert, nontoxic and nonflammable
v) Rapid drying rate
vi) No environmental pollution
Mostly solvents are used either alone or in combination with water, ethanol, methanol, isopropanol, chloroform, acetone, methylene chloride, etc. Water is more used because no environmental and economic considerations. For drugs that readily hydrolyze in presence of water, non aqueous solvents are used.
III. Plasticizers (1)
As solvent is removed, most polymeric materials tend to pack together in 3-D honey comb arrangement. “Internal” or “External” plasticizing technique is used to modify quality of film. Combination of plasticizer may be used to get desired effect. Concentration of plasticizer is expressed in relation to the polymer being plasticized. Recommended levels of plasticizers range from 1-50 % by weight of the film former. Commonly used plasticizers are castor oil, PG, glycerin, lower molecular weight (200-400 series), PEG, surfactants, etc. For aqueous coating PEG and PG are more used while castor oil and spans are primarily used for organic-solvent based coating solution. External plasticizer should be soluble in the solvent system used for dissolving the film former and plasticizer. The plasticizer and the film former must be at least partially soluble or miscible in each other.
Colourants can be used in solution form or in suspension form. To achieve proper distribution of suspended colourants in the coating solution requires the use of the powdered colourants (<10 microns). Most common colourants in use are certified FD & C or D & C colourants. These are synthetic dyes or lakes. Lakes are choice for sugar or film coating as they give reproducible results. Concentration of colourants in the coating solutions depends on the colour shade desired, the type of dye, and the concentration of opaquant-extenders. If very light shade is desired, concentration of less than 0.01 % may be adequate on the other hand, if a dark colour is desired a concentration of more than 2.0 % may be required. The inorganic materials (e.g. iron oxide) and the natural colouring materials (e.g. anthrocyanins, carotenoids, etc) are also used to prepare coating solution. Magenta red dye is non absorbable in biologic system and resistant to degradation in the gastro intestinal track. Opasray (opaque colour concentrate for film coating) and Opadry (complete film coating concentrate) are promoted as achieving less lot-to-lot colour variation.
These are very fine inorganic powder used to provide more pastel colours and increase film coverage. These inorganic materials provide white coat or mask colour of the tablet core. Colourants are very expensive and higher concentration is required. These inorganic materials are cheap. In presence of these inorganic materials, amount of colourants required decreases. Most commonly used materials are titanium dioxide, silicate (talc &aluminum silicates), carbonates (magnesium carbonates), oxides (magnesium oxide) & hydroxides (aluminum hydroxides). Pigments were investigated in the production of opaque films and it was found that they have good hiding power and film-coated tablets have highlighted intagliations.
VI. Miscellaneous coating solution component (1)
Flavors, sweeteners, surfactants, antioxidants, antimicrobials, etc. may be incorporated into the coating solution.
(1, 2, 13)
This type of coating is used to protect tablet core from disintegration in the acid environment of the stomach for one or more of the following reasons:
i) To prevent degradation of acid sensitive API
ii) To prevent irritation of stomach by certain drugs like sodium salicylate
iii) Delivery of API into intestine
iv) To provide a delayed release component for repeat action tablet
Several kinds of enteric layer systems are now available
One layer system - The coating formulation is applied in one homogeneous layer, which can be whites-opaque or coloured. Benefit is only one application needed.
Two layer system - To prepare enteric tablets of high quality and pleasing appearance the enteric formulation is applied first, followed by coloured film. Both layers can be of enteric polymer or only the basic layer contains enteric polymer while top layer is fast disintegrating & water-soluble polymer
Ideal properties of enteric coating material are summarized as below
i) Resistance to gastric fluids
ii) Susceptible/permeable to intestinal fluid
iii) Compatibility with most coating solution components and the drug substrate
iv) Formation of continuous film
v) Nontoxic, cheap and ease of application
vi) Ability to be readily printed
Polymers used for enteric coating are as follow
i.Cellulose acetate phthalate (CAP)
It is widely used in industry. Aquateric is reconstituted colloidal dispersion of latex particles. It is composed of solid or semisolid polymer spheres of CAP ranging in size from 0.05 - 3 microns. Cellulose acetate trimellitate (CAT) developed as an ammoniated aqueous formulation showed faster dissolution than a similar formulation of CAP. Disadvantages include: It dissolves above pH 6 only, delays absorption of drugs, it is hygroscopic and permeable to moisture in comparison with other enteric polymer, it is susceptible to hydrolytic removal of phthalic and acetic acid changing film properties. CAP films are brittle and usually used with other hydrophobic film forming materials.
ii. Acrylate polymers
Eudragit®L & Eudragit®S are two forms of commercially available enteric acrylic resins. Both of them produce films resistant to gastric fluid. Eudragit®L & S are soluble in intestinal fluid at pH 6 & 7 respectively. Eudragit®L is available as an organic solution (Isopropanol), solid or aqueous dispersion. Eudragit®S is available only as an organic solution (Isopropanol) and solid.
iii Hydroxy propyl methyl cellulose phthalate
HPMCP 50, 55 & 55-s (also called HP-50, HP-55 & HP-55-s) is widely used. HP-55 is recommended for general enteric preparation while HP-50 & HP-55-s for special cases. These polymers dissolve at a pH 5-5.5.
iii. Polyvinyl acetate phthalate
It is similar to HP-55 in stability and pH dependent solubility.
= Enteric sugar coating
Here the sealing coat is tailored to include one of the enteric polymers in sufficient quantity to pass the enteric test for disintegration. The sub coating and subsequent coating steps are then as for conventional sugar coating.
Enteric film coating
Enteric polymers are capable of forming a direct film in a film coating process. Sufficient weight of enteric polymer has to be used to ensure an efficient enteric effect. Enteric coating can be combined with polysaccharides, which are enzyme degraded in colon e.g. Cyclodextrin & galactomannan.
Controlled release coating
Polymers like modified acrylates, water insoluble cellulose (ethyl cellulose), etc. used for control release coating.
This type of coating requires a specialization tablet machine. Compression coating is not widely used but it has advantages in some cases in which the tablet core cannot tolerate organic solvent or water and yet needs to be coated for taste masking or to provide delayed or enteric properties to the finished product and also to avoid incompatibility by separating incompatible ingredients.
Electrostatic coating is an efficient method of applying coating to conductive substrates. A strong electrostatic charge is applied to the substrate. The coating material containing conductive ionic species of opposite charge is sprayed onto the charged substrate. Complete and uniform coating of corners and adaptability of this method to such relatively nonconductive substrate as pharmaceutical is limited.
Coating is applied to the tablet cores by dipping them into the coating liquid. The wet tablets are dried in a conventional manner in coating pan. Alternative dipping and drying steps may be repeated several times to obtain the desired coating. This process lacks the speed, versatility, and reliability of spray-coating techniques. Specialized equipment has been developed to dip-coat tablets, but no commercial pharmaceutical application has been obtained.
Vacuum film coating
Vacuum film coating is a new coating procedure that employs a specially designed baffled pan. The pan is hot water jacketed, and it can be sealed to achieve a vacuum system. The tablets are placed in the sealed pan, and the air in the pan is displaced by nitrogen before the desired vacuum level is obtained. The coating solution is then applied with airless spray system. The evaporation is caused by the heated pan, and the vapour is removed by the vacuum system. Because there is no high-velocity heated air, the energy requirement is low and coating efficiency is high. Organic solvent can be effectively used with this coating system with minimum environmental or safety concerns.
Three general types of equipments are available
1.Standard coating pan
e.g., Pellegrin pan system
Immersion sword system
Immersion tube system
2.Perforated pan system e.g.,Accela cota system
3.Fluidized bed coater
This value represents the quantity of water or solvent that can be removed during the coating process which depends on the quantity of air flowing through the tablet bed, temperature of the air and quantity of water that the inlet air contains.
The coating contains the ingredients that are to be applied on the tablet surface and solvents which act as carrier for the ingredients.
Tablet surface area
It plays an important role for uniform coating. The total surface area for unit weight decreases significantly from smaller to larger tablets. Application of a film with the same thickness requires less coating composition. In the coating process only a portion of the total surface is coated. Continuous partial coating and recycling eventually results in fully coated tablets.
Tablet coaters use the expression “coating efficiency” a value obtained by dividing the net increase in coated tablet weight by the total nonvolatile coating weight applied to the tablet. Ideally 90-95 % of the applied film coating should be on the tablet surface. Coating efficiency for conventional sugar coating is much less and 60% would be acceptable. The significant difference in coating efficiency between film and sugar coating relates to the quantity of coating material that collects on the wall.
The sugar coating involves several steps like, sealing, subcoating, colour coating and printing.
Sugar coating process yields elegant and highly glossed tablet.
Newer techniques utilize spraying systems and varying degree of automation to improve coating efficiency and product uniformity.
Film coating is deposition of a thin film of polymer surrounding the tablet core.
Film coating is more favored than sugar coating because weight increase is 2-3%, single stage process, easily adaptable to controlled release, it retains colour of original core, high adaptability to GMP, automation is possible, etc.
Accela cota and fluidized bed equipments are widely used for film coating.
Basic formula is obtained from past experience or from literature and modifications are made accordingly. Common modifications are to alter polymer-to-plasticizer ratio or addition of different plasticizer/polymer. Experimentation of this type can be best achieved by fractional factorial study.
Materials used in film coating include film formers, solvents, plasticizers, colourants, opaquant-extenders, surfactant, anti oxidant, etc.
Widely used film formers are Hydroxy Propyl Methyl Cellulose (HPMC),Methyl Hydroxy Ethyl Cellulose (MHEC), Ethyl Cellulose (EC), Hydroxy Propyl Cellulose (HPC), Povidone (four grades available i.e. K-15, K-30, K-60and K-90), Sodium carboxy methyl cellulose, Polyethylene glycols (PEG) and Acrylate polymers (Eudragit®, Eudragit®RL, Eudragit®RS, Eudragit®E) are used for film coating. Eudragit®L & S are used for enteric coating. Eudragit®RL, Eudragit®RS, Eudragit®S are available as organic solution and solid while Eudragit®L and Eudragit®E are available as organic, solid or aqueous dispersion.
Quality of film can be modified by plasticizer. Commonly used plasticizers include PG, glycerin, low molecular weight PEG, castor oils, etc. Castor oil and spans are more used for organic-solvent based coating solution while PE and PEG are used for aqueous coating.
FD & C or D & C certified colourants are used. Lakes are choice for film coating as they give reproducible results. Opaspray® (opaque colour concentrate for film coating) and Opadry® (complete film coating concentrate) are promoted as achieving less lot-to-lot variation.
Colourants are expensive and higher concentration is required. So materials like titanium dioxides, silicates, and carbonates are used to provide more pastel colours and increase film coverage.
Enteric coating is used to protect tablet core from disintegration in the acid environment of stomach to prevent degradation of acid sensitive API, prevent irritation to stomach by certain drugs, delivery of API into intestine, to provide a delayed release components for repeat action, etc.
Several kinds of enteric layer systems are available like one layer system and two-layer system. Polymers used for enteric coating are cellulose Acetate Phthalate (CAP), Acrylates (Eudragit®L and Eudragit®S, Hydroxy Propyl Methyl Cellulose Phthalate (HPMCP50, HPMCP55 & HPMCP 55s) and polyvinyl acetate phthalate
Enteric sugar coating:
Here sealing coat is modified to comprise one of the enteric polymers in sufficient quantity to pass the enteric test for disintegration. The sub coating and subsequent coating steps are then as for conventional sugar coating.
Enteric polymers are capable of forming a direct film in a film coating process. Sufficient weight of enteric polymer has to be used to ensure an efficient enteric effect.
Enteric coating can be combined with polysaccharides, which are enzymatically degraded in colon. For example, Cyclodextrin & Galactomannan.
Controlled release coating: