Sugar coating of pharmaceutical dosage form

Tablet Coating Process: Sugar Coating

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Sugar coating has long been the traditional method of coating pharmaceutical dosage forms. The process has its origin in the confectionery industry and has been used in the pharmaceutical industry since the late 19th century. The process of sugar coating involves the successive deposition of aqueous sugar solution on the tablet cores as they are rotated and tumbled in a revolving pan by spraying sugar solution or suspensions into pans and drying off the solvent.

Sugar coating is used in immediate release applications to mask unpleasant taste and odour of some drugs or to improve aesthetic qualities of the product. It should be understood that the coating process will add some time to the overall disintegration of the tablet and may impact drug dissolution. This effect should be considered when formulating the core to ensure that the product meets disintegration and dissolution requirements stated in official compendia. For an enteric or sustained-release sugar-coated product, the formulation problem may become more complex to meet USP tablet disintegration and dissolution specifications. The selection of the core tablet and coating materials becomes more important for these applications and requires proper evaluation to assure long-term chemical and physical stability.

Sugar coatings are essentially aqueous based, unless a seal coat (e.g., alcoholic confectioners glaze) is required to protect the core tablet from water used in the sugar-coating process. Although the sugar-coating process is lengthy and labour intensive, coating materials are inexpensive and readily available.

Ideal characteristics of sugar-coated tablets

  • Sugar-coated tablets should have a smooth, rounded contour, with even colour coverage and a high degree of gloss.
  • Sugar-coated tablets must meet requirements as specified in official compendia.
  • Those tablets that have been imprinted should show distinct print with no smudging or broken print.

Raw materials used in sugar coating

Because sugar-coating process consists of various steps, a variety of additives may be incorporated into each type of formulation to achieve a particular function. These include:

i. Sucrose, other sugars, and sugar alcohols

As expected, the major ingredient used in sugar-coating process is sugar (primarily sucrose), although this may be substituted by other sugars and sugar alcohols (such as glucose, lactose, maltitol, mannitol, isomalt, sorbitol, xylitol, and sugar mixtures such as invert sugar and starch sugars) for low calorie diabetic products (typically in the candy industry) and for the fact that sucrose cause dental caries.

Sucrose is used in concentrations ranging between 50-60%, since syrups with a sugar content of less than 65% are stable at room temperature without crystallization occurring.

ii. Binders

Binders increase the strength and elasticity of the coating by forming bonds and thus a coherent matrix. Examples of binders used in sugar coating include polyvinyl acetate (PVA), polyvinyl pyrrolidone (PVP), carboxymethyl starch, dextrin, acacia gum, gelatin, agar-agar, sodium alginate, cellulose ethers, and starches.

iii. Fillers

Fillers build up the structure and adds mass to the coatings. E.g., precipitated calcium carbonate, talc, kaolin, dextrin, powdered acacia, corn starch, and calcium sulfate.

iv. Colourants

They add colour to the coatings and covers imperfections which may appear in the tablet core. Examples include dyes, lakes (aluminum lakes) and pigments (titanium dioxide or other inorganic colouring agents).

v. Antiadhesives, Lubricants and Glidants

These materials reduce friction between coated tablets and thus prevent dust formation during drying. Examples include talc and colloidal silicon dioxide.

vi. Flavouring agents

Flavours improve and enhance the acceptability and palatability of the dosage form in order to maximize patient compliance. E.g., cinnamon, fruit flavours etc.

vii. Suspension stabilizers

They prevent phase separation or sedimentation of the coating suspension while it is being applied during the coating process. Examples include surface active agents (emulsifying agents, bentonite) or thickening agents.

viii. Smoothing agents

These materials smoothen out the surface of the coatings by lubricating and binding the fines that may be created during the coating process. Example include a combination of syrup and acacia gum.

ix. Polishing agents

Polishing agents enhance the reflectivity and intensity of the colour of the coatings. Beeswax and carnauba wax are good examples of polishing agents used in sugar coating process.

Techniques involved in sugar coating

The three techniques commonly used in sugar-coating process include:

a.        Plain sugar coating

This technique involves the application of syrup at room temperature. This coating technique includes 3 steps:

  1. Application of coating formulation onto the tablet cores
  2. Distribution of formulation on the core surfaces, and
  3. Drying to increase the strength of each coating layer.

Note that the time required for distribution and drying is critical to obtain a smooth even coating.

b.      Lamination process/ Two-component coating process

Compared to the plain sugar-coating technique, the lamination coating is a more complicated technique involving two steps:

  1. Application of a syrup or binder solution first in a slight excess amount, and
  2. Dusting with a powder to bind the excess solution

In order to obtain a reasonable weight increase within a short period of time, adjustment must be made between powder and liquid quantities and process performed by skillful operators.

c.       Hot sugar coating

As suggested by the name, hot sugar coating simply involves the application of heated syrup on tablet core. The syrup is heated above room temperature to reduce the viscosity of the syrup.  Attempts to prevent crystallization of sugar during processing may make this technique more complicated and more expensive since all equipment parts used must be insulated and heated.

Steps involved in sugar coating

Sugar-coating process consists of various steps, each designed to achieve a particular function. A typical sugar-coating process encompasses six stages:

  1. Sealing of the tablet core
  2. Subcoating
  3. Smoothing
  4. Colour coating`
  5. Polishing
  6. Printing

1. Sealing of the tablet core (Waterproofing/ Protective coating)

Seal coating involves the application of specialized polymer-based coating (either by ladle or spray techniques) directly to the tablet core. It is an optional step but is usually required to prevent the tablet core and its contents from absorbing water, softening, and initiating disintegration during the subsequent steps of the sugar-coating process. Sealing also prevents certain types of materials (e.g. oils, acids, etc.) from migrating to the tablet surface and spoiling the appearance.

In a manual seal-coating operation, the sealant which usually consist of alcoholic solutions of resins (approximately 10–30% solids) is evenly and gently poured or sprayed over the tumbling tablet bed (preheated to 40oC). Warm air is then blown into the pan during the coating to hasten the drying and to prevent tablets from sticking together.

The quantities of material applied as a sealing coat will depend primarily on tablet and batch size. Another variable is tablet porosity because 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 properly sealed.

Because most sealing coats develop a degree of tack (stickiness) at some time during the drying process, detackifiers, such as asbestos-free talc, are often used to minimize the risk of “twinning” or clumping.

Excessive use of talc may cause problems, firstly, by imparting a high degree of slip to the tablets, thus preventing them from rolling properly in the pan, and secondly by creating a surface that, at the beginning of the subsequent subcoating stage, is very difficult to wet. Such poor wetting often results in uneven subcoat buildup, particularly on the tablet edges. If there is a tendency for either of these problems to occur, one solution is to replace part or all of the talc with some other material such as terra alba, which will form a slightly rougher surface.

Common materials used as sealants include shellac, zein, hydroxypropyl methylcellulose (HPMC), cellulose acetate phthalate (CAP), or polyvinyl acetate phthalate (PVAP). While use of shellac has been universal, this natural polymer can undergo further polymerization on storage, causing the seal coat to become completely insoluble to the point where bioavailability of the active drug substance may be compromised. This problem can be minimized either by incorporating small amount of PVP into the shellac-based seal coat formulation or by using one of the other more stable polymers (such as PVAP). If the final product is to have enteric properties, this result can be achieved using one of the enteric polymers (such as PVAP or CAP) as the basis for the seal coat and ensuring that sufficient coating material is applied.

2. Subcoating

This step is regarded as the first major step in sugar-coating process. It involves the application of large quantities of sugar-coatings to the tablet core, significantly increasing the tablet weight by 50 – 100 %. Subcoating provides the rapid buildup necessary to round up the tablet edge. It also provides the foundation for smoothing and colour coating with any weakness in the final sugar coat often being attributable to weaknesses in the subcoat.

There are two techniques for the subcoating application; lamination process and suspension subcoating process; each with its distinct features and advantages.

i. Lamination process

The lamination process is perhaps the older of the two techniques used, and involves application of a “glue” (in the form of an aqueous solution of a suitable gum, such as gum acacia, or even gelatin) in quite substantial quantities to the sealed tablet cores. Once this solution has been distributed uniformly throughout the tablet mass, it is followed by a liberal dusting of powder (which serves to reduce tack and facilitate tablet buildup) and drying. This process of application of gum solution, spreading, dusting, and drying is repeated until a satisfactory coating is achieved.

While this method has proved to be very effective, particularly where there is difficulty in covering edges, it is important to ensure that a careful balance is achieved between the relative amounts of gum solution and dusting powders used. The use of inadequate dusting powders increases the risk of sticking and twinning, whereas its excessive use can create tablets that have brittle coatings. While achievement of quality results with the lamination process typically requires employment of skilled operators, there is no doubt that this type of process can permit rapid buildup of the coating. On the downside, the lamination process can be messy, more difficult to use by less-skilled operators, and more difficult to automate (as both powders and liquids are involved).

Table showing binder solution formulation used in lamination subcoating process
Examples of binder solution used in lamination subcoating process
Table showing dusting powder formulations used in lamination subcoating process
Examples of dusting powder formulations used in lamination subcoating process

ii. Suspension subcoating process

This is an alternative approach used particularly when using an automated dosing system.  The process involves the application of a suspension subcoat formulation (essentially a coating formulation where the powdered materials used in the more traditional lamination process are dispersed into the gum-based solution). Employing suspension subcoating approach not only reduces the complexity of the process, but also enables the less-experienced operator to achieve satisfactory results.

Table showing typical suspension subcoating formulation
Examples of Suspension Subcoating Formulations

3. Smoothing or Grossing

In order to manufacture quality sugar-coated tablets, it may be necessary to smooth out the tablet surface and fill the irregularities generated during subcoating. Smoothing usually can be accomplished by applying sucrose-based solution with or without additional components such as starch and calcium carbonate. This is followed by drying until the tablets are properly rounded and smooth. Drying may last up to 20 minutes or more depending on the scale of operation. In some operations, 5 to 25 applications may be required to achieve smooth tablets that are suitable for the next stage.

Depending on the degree of smoothing required, the smoothing coating may simply consist of a 60-70% sucrose syrup, that is often coloured with titanium dioxide (an opacifier/whitening agent) to achieve the desired level of whiteness, and possibly tinted with other colourants to provide a good base for subsequent application of the colour coat.

4. Colour coating/ Colouring

This is one of the most important steps in the sugar-coating process as it has immediate visual impact that is associated with overall quality. It involves the multiple application of syrup solutions (60–70% sugar solids) containing the requisite colouring materials necessary to achieve the desired shade. As with film coating colours, sugar-coating colourants may be subdivided into either water-soluble dyes or water-insoluble pigments. The nature of the colourant selected often defines the type of colour-coating procedure to be used.

Traditionally, water-soluble dyes have been used because they produce the most elegant sugar-coated tablets but in order to speed up the coating process, minimize colour migration problems, and ensure colour reproducibility from batch-to-batch, water-soluble dyes have gradually been replaced with water-insoluble pigments in pharmaceutical tablet coating. Tablet colour coating with water-insoluble pigments have demonstrable advantages over water-soluble dyes, two important ones being:

  1. Lack of solubility in aqueous media which eliminates colour migration during drying
  2. Superior light stability.

Although water-insoluble pigment-based colour coatings are by no means foolproof, they will permit more abuse than a water-soluble dye colour-coating process and are easier to use by less-skilled coating operators.

Note: The actual colourants used must comply with regulations promulgated by the national legislation of the country where the products are to be marketed.

5. Polishing/ Glossing

Sugar-coated tablets are, by nature very dull in appearance (i.e., they have a matte surface finish), and thus requires a separate polishing step to give them the high degree of gloss that typifies finished sugar-coated tablets. Polishing is accomplished by applying mixtures of waxes either as powders (usually in a finely milled form) or as solutions/dispersions in various organic solvents to the coated tablets in a polishing pan.

Some polishing systems which are currently in use include:

  • Organic-solvent-based solutions of waxes (beeswax, carnauba wax, candelilla wax, hard paraffin wax)
  • Alcoholic slurries of waxes                                
  • Finely powdered mixtures of dry waxes
  • Pharmaceutical glazes (typically alcohol solutions of various forms of shellac, often containing additional waxes).
  • Mineral oil.

While methods to achieve a desirable gloss tend to vary considerably, it is generally recommended that tablets should be trayed overnight in a suitable atmosphere (prior to polishing) to ensure that they are sufficiently dry. Excessively high moisture levels in tablets submitted for polishing will not only make achievement of a good gloss difficult but will also increase the risk of “blooming” and “sweating” of the coated tablet on standing.

6. Printing

It is common practice to identify all oral solid dosage forms with a product name, company name or logo, dosage strength or other distinctive symbol. For sugar-coated tablets, such identification involves the application of special edible inks to the coated tablet surface by means of a printing process known as offset rotogravure.

Printing prior to polishing enables the ink to adhere more strongly to the tablet surface, but any legend may subsequently be removed by either friction or as a result of contact with organic solvents during the polishing process. Printing after polishing avoids the problem of print rub-off during polishing, but branding inks do not always adhere well to the waxed tablet surface. Adhesion of printing inks can be enhanced by application of a modified shellac, preprint base solution prior to printing.

Note: Alternative printing processes, such as ink-jet and pad-printing processes, have also gained acceptance.

Sugar coating defects, causes and remedies

In any coating process, a variety of problems may be encountered. Often such problems may be related to formulation issues that have been compounded by those associated with processing.

a. Chipping of coatings

This is caused by excessive use of insoluble fillers and pigments. It can be resolved by addition of small quantities of polymers (such as cellulosics, PVP, acacia or gelatin) to one or more of the various coating formulations.

b. Cracking of the coatings

Tablet cores that expand, either during or after coating, are likely to cause the coating to crack. Such expansion may result from stress-relaxation of the core after compaction (a phenomenon which is known to occur, for example, with ibuprofen) or moisture absorption by the tablet core. Expansion due to post compaction stress relaxation can be resolved by extending the time between the compaction event and commencement of sugar coating, whereas moisture sorption can be minimized by appropriate use of a seal coat.

c. Non-drying of the coating

This is the inability of sugar coatings (especially those based on sucrose) to dry properly. It is often an indicator that excessive levels (greater than 5%) of invert sugar is present. Inversion of sucrose is worsened by maintaining sucrose syrups at too high a temperature under acidic conditions for a long period of time. Such conditions occur when sugar-coating solutions containing aluminum lakes are kept hot for too long; or such sugar-coating formulations are constantly being reheated to redissolve sugar that is beginning to crystallize out. The remedy, of course, is to avoid the excess heating of the sucrose syrup under acidic conditions.

d. Twinning (buildup of multiples)

By their very nature, sugar-coating formulations are very sticky, particularly as they begin to dry, and allow adjacent tablets to stick together. Buildup of multiples really becomes a problem when the tablets being coated have flat surfaces which can easily come into contact with one another. This can be particularly troublesome with high-dose, capsule-shaped tablets that have high edge walls. Appropriate choice in tablet punch design can be effectively used to minimize the problem.

e. Uneven colouring

Because colour-coating stage of the sugar-coating process has a major impact on final tablet appearance, the process is critical to ultimate tablet quality. Uneven distribution of colour particularly with the darker colours, is often visually apparent and thus a major cause of batch rejection. Many factors may contribute to this type of problem, including:

  1. Poor distribution of coating liquids during application – This may be caused by poor mixing of tablets in the coating process, or failure to add sufficient liquid to coat completely the surface of every tablet in the batch. This can be resolved by adding sufficient coating liquid and ensuring that it is properly mixed.
  2. Colour migration of water-soluble dyes while the coating is drying – This can be minimized by changing the solvent system or optimizing the drying condition.
  3. Unevenness of the surface of the subcoat when using dye-coloured coatings – This unevenness causes a variation in thickness of the transparent colour layer that is perceived as different colour intensities. It can be resolved by achieving the required smoothness during the subcoat application.
  4. Washing back” of pigment-coloured colour coatings – While pigments do not migrate on drying, if excessive quantities of coating liquid are applied during the colouring process, there is a tendency for the previously applied (and dried) colour layers to be redissolved and distributed nonuniformly; thus, giving rise to nonuniform appearance. This problem is particularly noticeable for formulations predominantly coloured with aluminum lakes where the level of opacifying pigments (such as titanium dioxide) is low (i.e., dark colours). This can be prevented by avoiding excessive use of coating liquid, replacing aluminum lake or using a combination of dyes and pigments.
  5. Excessive drying between colour applications – This can cause erosion of the colour layer and contributes to unevenness in the colour coat. It can be corrected by reducing drying rate or temperature.

f. Blooming and Sweating

Residual moisture (in finished sugar-coated tablets) can often be a problem. Over a period of time, this moisture can diffuse out and affect the quality of the product. Moderate levels of moisture egress cause the polish of the product to take on a fogged appearance, a phenomenon often termed blooming. At higher levels (of moisture egress), the moisture may appear like beads of perspiration on the tablet surface. This second phenomenon, often called sweating, can be much more serious since tablets stored in closed containers will ultimately stick together.

Obtaining appropriate levels of moisture in the sugar coating is conducive to good polish characteristics and avoidance of sweating and blooming. Thus, great care has to be taken with the drying stage at the end of each application of coating liquid as well as to selection of appropriate racking/ drying of tablets prior to polishing.

g. Marbling

One of the secrets to achieving a high-quality sugarcoated product is to ensure that colour is uniformly distributed in the colour layer, and that a smooth coating surface is obtained at the end of the application of the colour coating prior to polishing. Failure to achieve the requisite smoothness often results in a marbled appearance on polishing. This problem occurs as the result of the collection of wax in the small surface depressions of a rough coating and is particularly evident with darker colours. It can be resolved by ensuring that a smooth surface is achieved at the end of colour coating.

Recovery of reject sugar-coated tablets

Owing to the amount of material applied as a coating in the sugar-coating process, it is not appropriate to grind up reject sugar-coated tablets for recompaction. One potentially viable recovery procedure (although one not without its difficulties because of handling problems) is to wash off the sugar coating by carefully dipping the coated tablets (held on a screen) into a water bath until sufficient coating is removed such that on subsequent refinishing, the desired quality is achievable. Once the requisite quantity of coating is removed, the tablets can be dried by tumbling in a coating pan under a warm air stream (50°C). Such a procedure must obviously be validated to ensure that overall product quality is not compromised.

Differences between sugar coating and film coating

Table Showing the differences between Sugar coating and Film coating

Examples of sugar-coated tablets

  • Brufen – Ibuprofen 400 mg (Mylan Products Limited)
  • Reasulf tablets – dried ferrous sulphate BP 200 mg (Reagan Remedies Ltd.)
  • Premarin – Conjugated oestrogens 625 mcg (maroon) and 1.25 mcg (yellow) (Pfizer Limited)
  • Advil – Ibuprofen tablet BP 200 mg (Pfizer Consumer Healthcare)
  • Colofac tablets – Mebeverine HCl 135 mg  (Mylan Laboratories SAS)
  • Ebu-200 – Ibuprofen tablet BP 200 mg (Me cure Industries Ltd)

Advantages of sugar coating

  • Sugar coating process utilizes inexpensive and readily available raw materials.
  • Constituent raw materials used are widely accepted with few regulatory problems (with the exception of perhaps colours)
  • The process is easily documented and controlled to meet modern GMP standards.
  • Inexpensive, simple equipment can be used.
  • Sugar coating process is generally not as critical (as film coating) and recovery (or rework) procedures are more readily accomplished.
  • Products are usually aesthetically appealing and have wide consumer acceptability.
  • Advancement in science and technology have greatly reduced the variability in coating obtained with manually operated coating pans.

Disadvantages of sugar coating

  • The process is tedious and time consuming.
  • The achievement of high esthetic quality often requires the expertise of highly skilled technicians.
  • The size and weight of the coated tablets results in increased packaging and shipping costs.
  • Finished products may vary slightly in size from batch to batch and within a batch.

Conclusion

While the popularity of sugar coating has certainly declined due to the advent of film-coated tablets (as a result of the improved mechanical properties of the latter coating), this process is still used by many companies that have invested in the complete modernization of the process.

References

  • Allen L. V and Ansel H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.
  • Aulton, M. E and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
  • Avis, K. E., Shukla, A. J. and Chang, R. (1998). Pharmaceutical Unit Operations: Coating London, Taylor & Francis Group, LLC.
  • Coating from http://cosarpharm.com/fa/wp-content/uploads/2015/12/Coating.pdf [accessed Jan 7 2019]
  • Cole, G. (2002). Pharmaceutical Coating Technology. UK,Taylor & Francis Ltd.
  • Felton, L.A. (2012). Remington Essentials of Pharmaceutics. UK: Pharmaceutical Press.
  • Lieberman, H. A., Lachman, L. and Schwartz, J. B. (1990). Pharmaceutical Dosage Forms: Tablets. New York: Marcel Dekker, Inc.
  • Ofoefule, S. I. (2002). Textbook of Pharmaceutical Technology and Industrial Pharmacy. Nigeria: Samakin (Nig.) Enterprise.


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