Understanding Tablet Coating ProcessPrint
Tablets that are compressed are coated with sugar layer and may be colored or uncolored depending on the tablet’s purpose. The sugar coating is water soluble making it easier to dissolve quickly when it comes into contact with any liquid matter. One purpose for the sugar coating is to protect and act as barrier for the drug inside the tablet from outside conditions as well as enclose the unsavory taste of the drug that some patients may find unpalatable. Aside from this, the coating is also used to improve the tablet’s appearance as well as allows the pharmaceutical companies to imprint information on the tablet’s surface. Sugar coating insulates, smooths out the tablet’s core, and colors; it also modifies the release of the drug in the system.
There are a variety of benefits with Sugar coating; however, one disadvantage with it is that it requires additional time and specialization or expertise when it comes to the coating process thus increasing the expenses associated with it.
Four Processes of Sugar Coating
- Sealing (Water proofing) – sealing involves hardening the surface area of the tablet by providing a moisture barrier.
- Grossing (Smoothing) – this involves smoothing out the coated area while increasing the size of the tablet to the required size.
- Coloring – provides the tablet the appropriate color and finished look.
- Polishing – finishes the tablet piece by polishing and making the tablet glossy
Sealing (Water Proofing)
Before any sugar or syrup is added to the tablet, the core must be sealed and thoroughly dried first as well as be free from any leftover solvents. Once the core is dry, a coat is applied to protect the core from any moisture and also hardens the surface area to prevent any undesirable effects. The core of the tablet is usually weak and has high disintegration and as such would likely be the first to disintegrate during the coating process. The sealants used are usually water soluble and formulated from organic solutions.
The sealing coat formulation depends on the porosity of the tablet since highly porous ones would likely soak up the solution preventing this from coating other areas of the tablet. That said, a second coating or more would be applied to ensure that the core is effectively sealed.
Sealants that are commonly used includes:
- Cellulose acetate phthalate
- Polyvinylacetate phthalate
The sugar coating process actually starts in the Subcoating stage whereby the tablet’s sides are rounded up to the desired look. This is also where smoothing and color is added to the tablet.
2 ways of Subcoating:
- A gum based solution is applied to the tablet followed by application of dust powder and drying the tablet. The process is repeatedly done until the desired shape is reached.
- Dry powder is applied followed by gum/sucrose solution and then drying of the tablet
Subcoating therefore involves alternating gum solution with dusting powder until the desired shape and consistency is achieved. Excess water is removed after every syrup application.
Typical Binder Solution Formulation For Subcoating
|Gum acacia (powdered)||8||8.7|
|Distilled water||to 100||to 100|
Typical Dusting Powder Formulation For Subcoating
|Talc, asbestos free||25.0||61.0|
|Gum acacia (powdered)||2.0||-|
Typical Suspension Subcoating Formulation
|Talc, asbestos free||12.0|
The Grossing or smoothing process involves refinishing the tablet so that a smooth and finished look is achieved; this is done by smoothing and filing out the irregular patterns or areas of the tablet. This process would also increase the size of the tablet to a predetermined size.
If there are high level of irregularities on the tablet, the worker would use grossing syrup which contains suspended solids ensuring a better result. An application of approximately 60-70% of sugar solid is enough to smooth the tablet. The solution usually contains a mixture of starch, pigments, acacia, gelatin and opacifier if needed.
In certain instances, colour may be added in order to attain the desired hue if there are any differences in the coating.
Color coating is the most crucial stage in the process as multiple sugar solution is added to ensure that the predetermined color is achieved. Soluble dyes are used to achieve the color needed and are preferred as these stick to the surface of the tablet during the drying process. Nowadays however, pharmaceutical companies make use of insoluble certified lakes to replace the soluble dyes. The most useful one would be the use of predispersed opacified lake suspension in the color coating process.
To achieve the final look of the tablet, companies polish the tablet to make it look ideal. An application of wax such as carnuba wax, candelila wax, beeswax and hard paraffin is used to polish the tablets inside the pan
In other pharmaceutical companies, film coating is more favorable than sugar coating.
Comparison Between Film Coating And Sugar Coating
|FEATURES||FILM COATING||SUGAR COATING|
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 starts with enveloping the tablet’s core with a thin film of polymer. Traditional pans are used in the process, although recent innovations make use of more sophisticated equipment that have a higher automatic coating level. The polymer film is liquefied into solvent, and additives such as pigments and plasticizers are also mixed into the solvent. Once these are mixed together, it is then sprayed into a rotating bed. The drying process helps remove the excess solvent leaving behind a thin coating of the solvent around the core of the tablet.
Spray process is the preferred medium in coating the tablets with the film polymer. Accela cota is the perforated cylindrical drum used in assisting the drying of the tablets. The fluidized bed which is incorporated in the process makes it easier for the tablets to pass through the stream of air through the cylindrical bottom. The smaller cylindrical insert helps the tablets to move upwards while being exposed to spray mist being applied in the middle area. When using the fluidized bed coating, tablets with hardness >20N is used.
Film Coating Requirements:
The basic requirements are separated from the actual equipment being used and includes the right means of atomizing the spray liquid during application, proper mixing and agitation of the tablet bed, enough drying heat air to evaporate the solvent. This is crucial especially for liquid based sprays. Exhaust efficiency is also important to remove the solvent laden air and dust as well.
Developing the Coating Formulation:
The following questions should first be answered in order to determine if film coating is applicable:
- Is it important to mask the taste, odor or color of the tablet?
- Is it important to control the release of the drug?
- What are the specifications that need to be fulfilled during the developmental stage? (size, color, shape)
The size, color and even the shape of the tablet is important especially when it comes to marketing the final product and can have an impact on the marketing strategies of the company. An experienced formulator may consider the coating formulations that have been proven successful in the past. The use of spraying or casting is the first step in screening the film formulation. Cast film cabs are prepared by spreading the solution into several surfaces such as Teflon, aluminum foil or glass using a spreading bar to achieve the preferred thickness. Sprayed films on the other hand can be used by mounting a plastic coated surface in the coating pan.
The base formula for every coating is achieved by using previous formulas and modifications are added to the formula to improve the bond of the coating to the tablet’s core, reduce bridging of installations and increase the hardness of the coating among others. The amount or concentration level of the color and opaquant are fixed at a certain level to ensure the predetermined shade. Common alterations include the polymer to plasticizer ratio as well as the addition of different polymers to the coating formula.
- Film Formers (enteric or non-enteric)
- Opaquant Extenders
- Other components
Materials used in the film coating include:
- Solubility of the solvent
- pH-dependent solubility
- Capacity for an well-designed end product
- Constancy against outside conditions such as light, heat, moisture and substrate
- No changes in taste, color and smell
- Compatibility with other coating additives
- Nontoxic with no pharmacological actions
- Resistance to cracks
- Film formers should not result to bridging or filling
- Ideally compatible with imprints
Commonly Used Film Formers:
- HPMC - Hydroxy Propyl Methyl Cellulose
- The HPMC is a polymer that is ideal for processes such as air suspension and pan spray coating due to its solubility in organic, gastric fluid and other liquid solvent matter. It is available in different viscosity levels.
- Advantages – the HPMC is cheap, heat, light and moisture resistant, flexible, has no inherent smell or taste, does not affect the tablet’s disintegration and drug availability and colors and other additives can easily be added.
- Disadvantages – A mixture of the HPMC with other polymers is recommended as when use exclusively, it has the inclination to bridge or fill up the debossed tablet’s surface.
- MHEC - Methyl Hydroxy Ethyl Cellulose
- The MHEC is not as often used as the HPMC because of its few organic solvents. It is also available in different viscosity levels.
- EC - Ethyl Cellulose
- The EC is completely insoluble in liquid such as water and gastric and as such, it must be used in combination with other water soluble additives such as the HPMC. The EC viscosity level depends on the level of ethoxy used. The unplasticized EC films are often brittle and require modifiers in order to become pliable and be used in the film formulation. The aqua coat, for example, is an aqueous polymeric that utilizes EC. The pseudolatex system has low viscosity, high solids that have different properties making them different than the regular EC solution.
- HPC - Hydroxy Propyl Cellulose
- The HPC is water soluble when it is below 40C but insoluble above 45C and is soluble in other fluids such as gastric and other organic solvents. The HPC is flexible; however it becomes tacky while drying and is used only as sub-coats and not for glass or color coating.
- The Povidone’s polymerization depends on the molecular weight of the item. It is available in 4 viscosity level – K-15, K-30, K-60 and K-90. The average molecular weight is – 10,000, 40,000, 160,000 and 360,000 respectively. The K-30 is commonly used as a binder and coating for tablet as it has an excellent solubility when it is exposed to liquid components such as water, intestinal fluid, gastric and even organic solvents. Povidone can also be cross-linked with other materials to form films that have enteric properties. Povidone can also be used to disperse colors to coat tablets.
- Sodium Carboxy Methyl Cellulose
- This agent is only ideal when dispersed in water in order to form colloidal solutions but is not the right choice as a coating for tablets that are based on organic solvents. Although the solution adheres to the tablet’s surface, the tablet becomes brittle when exposed to the solution. Partially dried films are considered as tacky and as such other additives are used to modify the composition. Viscosity levels range from medium, high and extra high
- PEG - Polyethylene glycol
- The PEG comes in two forms – 1. PEG with low molecular weight about 200-600 and is liquid at room temperature. These are used as plasticizers. 2. PEG with high molecular weights ranging from 900-8000S. The higher molecular weights PEG are whitish and often appear as wax at room temperature. Formulators mix the two forms to produce a film that is soluble when it comes in contact with gastric fluids.
- Acrylate polymers
- Acrylate polymers are marketed under the EudragitO with EudragitO as a cationic polymer. It is freely soluble when exposed to gastric fluids with up to 5 pH and becomes permeable and expandable when above the pH5. The polymers are available as organic solution for isopropanol (12.5%) and as solid or 30% as aqueous dispersion. The EudragitORL & RS are co-polymers that have low content of quaternary ammonium. The co-polymers are only available as solid materials or as organic solutions. They produce the films that are pH dependent (delayed in action).
Solvents are used to dissolve the polymers and other additives and transfer them to the surface area.
- Solvents should be able to disperse the polymer
- It should easily dissolve other additives added to the system
- Small concentration level of the polymer should not cause any problems for exceedingly viscous solution
- It should be non-toxic and non-flammable
- It should be odorless, colorless and tasteless
- Does not cause any environmental problems
- Have high drying rate
Most of the solvents used are by themselves; however some are combined with other solvents such as ethanol, chloroform, water, methanol, isopropanol, acetone and methylene chloride. Due to environmental and health concerns, water is the most commonly used additive; however for drugs that hydrolyze when they come into contact with water, other non-aqueous solvents are added.
Once the solvents are removed, the polymers tend to stick together creating a 3D honeycomb look. Plasticizing techniques – internal and external are used to change the film quality and a combination of the plasticizers maybe used to get the look desired. The concentrated level of plasticizer depends on the polymer that is being plasticized where the recommended level ranges from 1-50% depending on the film’s weight.
Castor oil, PG, glycerin, 200-400 series low molecular weight are the commonly used plasticizer. Castor oil is primarily used as a base for organic solvent solution; on the other hand, PEG and PG are commonly used for aqueous coating. The external plasticizers must be soluble in the solvent that is used to dissolve the plasticizer and film. The film former and the plasticizer must however be soluble even partially together.
The colourants used are available in solution and suspension form. In order to distribute the suspended colourant equally, the coating solution requires the use of powdered colourants. Certified FD, C and D/C colourants are the common ones used which are lakes and synthetic dyes. For sugar or film coating, lakes are ideal because these produce reproducible results.
The color shape, dye type and opaquant extender are some of the features needed to ensure the concentration of the coating solution. Concentration of < 0.01% will result in a lighter shade whereas 2.0% concentration level result in a darker color. Other additives include inorganic materials such as iron oxide and natural coloring such as carotenoids and anthrocyanins are used to prepare the coating solution. The color magenta red dye is non-absorbable in the biologic system and resistant to degradation when it approaches the gastro intestinal tract. To achieve less lot-to-lot color variations, OpasrayO and OpadryO are used.
These extenders are fine inorganic powder used to increase the fil coverage and provide more pastel color to the tablet. The white coat covers the core of the tablet. The colourants are expensive and a high level is needed; however the inorganic materials are more affordable. In the presence of the inorganic matters, the level of colourants decreases. Common materials used include:
- Titanium dioxide
- Silicate (talc/aluminum silicates)
- Carbonates (magnesium carbonates)
- Oxides (magnesium oxide)
- Hydroxides (aluminum hydroxides)
The pigments have excellent hiding power and intagliations for film-coated tablets.
Other solutions added include surfactants, flavors, antimicrobials, antioxidant and sweeteners.
Enteric coating involves coating the core of the tablet to protect the drug against the stomach acid including:
- Preventing the degradation of acid sensitivity
- Prevention of stomach irritation cause by sodium salicylate
- Delivery of the API into the intestine
- Delaying the release of the components for tablets
Enteric layering system:
- 1-Layer System – the formulation is coated in one consistent layer either in color or white-opaqued coloring. The benefits of the first layer is that only one application is needed.
- 2-Layer System – the enteric formulation is applied first after which the coloured film is applied next. Both of the layers can be of enteric layer, the basic layer can include the enteric polymer while the top layer can disintegrate and can be water-soluble.
Properties of Enteric Coating:
- Gastric fluid resistance
- Susceptible to permeable fluid
- Compatible to different coating solution components
- Development of uninterrupted film
- Non-toxic, affordable and can easily be applied
- Easily be imprinted
Enteric Coating Polymers
CAP - Cellulose acetate phthalate
CAP is commonly used in the industry. Aquateric is reconstructed colloidal diffusion of latex particles composed of solid or semisolid polymer spheres of CAP that range from 0.05 – 3 microns. CAT or Cellulose acetate trimellitate developed as ammoniated aqueous formulation showed a quicker dissolution than the same formulation of CAP.
- Dissolves < pH 6
- Delays drug absorption
- Permeable to moisture compared with other enteric polymer
- Susceptible to hydrolytic removal of phthalic
- Acetic acid changes film properties
- CAP films are fragile and usually used with other hydrophobic film
There are 2 forms of commercially available enteric acrylic resins - Eudragit(r)L & Eudragit(r)S which produce films that are resistant to gastric liquid. Both of them are soluble in intestinal fluid at pH 6 and 7. The L is available in organic, solid or aqueous distribution. The S on the other hand is only available as an organic and solid solution.
Hydroxy Propyl Methyl Cellulose Phthalate
Commonly used - HPMCP 50, 55 & 55-s - the 55 is also recommended for enteric preparation whereas the 50 and the 55-s are for distinct cases. The polymers dissolve at a pH of 5-5.5.
Polyvinyl acetate phthalate
The PAP is the same as that of the HP-55 in terms of stability and pH dependent solubility.
Enteric Sugar Coating
Enteric sugar coating involves the sealing coat being tailored to add one of the enteric polymers to pass the enteric test for disintegration. The sub and subsequent coating steps are for the traditional sugar coating process.
Enteric Film Coating
The enteric polymers are capable of forming a direct film in the coating process. To ensure an effective and efficient effect, sufficient weight of the polymer is needed. The coating can be mixed with polysaccharides which can degrade in the colon.
Controlled Released Coating
Controlled released coatings are polymers such as modified acrylates and water insoluble cellulose.
- Compressed coating – the coating requires a specialized tablet press machine. This type of coating is not popular but has some advantages including coating the tablet to mask the taste and protect the core from organic solvent or water. Other advantages include delaying the enteric properties and preventing the separation of the incompatible ingredients.
- Electrostatic coating – this is a method whereby coats are applied to the conductive substrates. A strong electrostatic charge is then applied to the substrate. The materials in the coating process contain conductive ionic species that are of opposite charge and then sprayed on the charged substrate. The comprehensive and constant coating of all the corners as well as the adaptability of the electrostatic coating to the nonconductive substrate is limited.
- Dip coating – this method involves the tablet’s core being dipped into the coating liquid. Once dipped in the solution, the tablets are then placed in a traditional coating pan to dry. The steps are repeated until the desired coating is achieved. Disadvantages for this process include the lack of versatility, speed as well as reliability that the spray technique is known for. Although specialized equipment has been developed for dip coating, no commercial application for it has been attained.
- Vacuum film coating – This procedure uses a specially designed baffled pan, whereby the pan is hot water jacketed and then sealed to achieve the vacuum state. The tablets are then placed in the sealed pan and the air is displaced by nitrogen before the vacuum level needed is achieved. Once the vacuum level is achieved, the coating solution is then applied to the tablets via airless spray system. The evaporation of the water is caused by the heated pan whereas the vapors are removed via the vacuum system. As there are no high velocity heated air, the energy needed is low but the coating efficiency is higher. The organic solvent is effective and ideal for the coating system as there are minimal safety and environmental concerns.
3 Equipment Types:
- Regular coating pan – Pelegrin, Immersion sword and Immersion tube
- Perforated pan – Accela cota, Hicoater, Glattcoater, Driacoated system
- Fluidized bed coater
- Air Capacity – this parameter denotes the water quantity or the solvent that is removed during the coating process. It depends on the air quantity that is flowing through the bed, air temperature and the water quantity that the inlet air contains.
- Coating Composition – the coating comprises the ingredients that have to be added to the surface of the tablet and the solvent used to act as the ingredient’s carrier.
- Tablet Surface Area – plays an important part in the uniform coating of the tablet. The total area for the unit decreases considerably depending on the size of the tablet. Film application of the same thickness needs less coating. During the coating process only a part of the total surface is coated. The continuous partial coating and recycling will eventually result in the tablet to be fully coated.
- Equipment Efficiency – coating efficiency is achieved by dividing the net increase in the weight by the total of the nonvolatile coating applied to the tablet. The ideal coating should be at 90-95%. An acceptable rate for conventional sugar coating is less with 60% as an acceptable rate. The important difference in coating efficiency between the film and the sugar depends on the amount of coating material that collects on the wall.
- The sugar coating process involves several steps including – sealing, color coating, subcoating and printing
- The sugar coating process produces highly glossed and distinct looking tablets
- Latest techniques make use of spray system and automation to increase coating efficiency and uniformity of the end product.
- The film coating involves coating the tablet core with thin film of polymer
- The film coating process is highly favored because the weight increases to 2-3%, only takes a single stage process, can be controlled with ease, easily retains the color of the original core, automation is possible and adaptability to GMP
- Film coating makes use of Accela cota and fluidized bed equipment
- The base formula makes use of old formulas and then modified to adapt to the current requirement. Common alterations include the ratio of polymer and plasticizer.
- Materials used include film formers, solvents, colourants, plasticizer, opaquant-extenders, anti-oxidant and even surfactant.
- Film formers that are widely used include HPMC, MHEC, EC, HPC, and organic solution, solid and aqueous dispersion.
- The quality of the film can be modified by using plasticizers such as PG, low molecular weight PEG, castor oil, spans and glycerins. The spans and castor oil is used for organic solvent based solution whereas the PEG and PE are for aqueous coating solution.
- Certified colourants such as FD & C or D & C are used. Lakes are preferred as they show viable results.
- Since colourants are expensive and a high concentration amount is needed, other materials are used such as silicates, carbonates and titanium dioxides are to increase the tablet coverage and as well as give the tablet a pastel color look.
- The enteric coating is used to protect the core of the tablet from disintegrating when exposed to the stomach acid, prevent acid sensitive API degradation, and stomach irritation, delivery of the API to the intestine tract and to provide a timed release of the components.
- There are 2 kinds of layering - 1 layer and 2 layer system. Polymers that are used include but are not limited to - CAP, HPMC, acrylates and polyvinyl acetate phthalate.
Enteric Sugar Coating
- The sealing coat is altered by adding one of the enteric polymers in sufficient number in order for it to pass the enteric test for dissolution. The sub-coating and succeeding coating steps are for conventional sugar coating.
- The enteric polymer has the ability to form a direct film during the film coating process. Sufficient weight must be used in order to have an efficient enteric effect.
- The enteric coating can be mixed with other compounds such as polysaccharides which can dissolve in the colon.
Controlled Release Coating
- Polymers such as ethyl cellulose and altered acrylates are used.