Defects in film coating process

Common Defects in Film Coating Process: Causes and Possible Solutions

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Polymeric film coating, in the formal sense, is a process that has been extensively used in pharmaceutical companies for over half a century. In spite of its relative longevity, it remains a complex process in which all technical issues and their impact are not always fully appreciated with the result that potential problems continue to arise with all too frequent regularity.

This article will focus on identifying the most common defects in film coating process, along with typical causes and possible solutions.

Characterizing problems encountered in film coating

Although problems encountered during film coating process can fall into a broad range of categories, by far the largest category is that associated with visual defects, often purely cosmetic in nature, which rarely impact the efficacy of the finished dosage form, except in the sense that they might lead to reduced patient confi­dence.

Defects associated with ­film-coated products can generally be classi­fied in this manner, namely those affecting:

  • Visual coated product quality
  • Coated product performance and functionality
  • Coated product stability
  • Processing ef­ficiencies and manufacturing costs

Defects in film-coated tablets

A number of technical problems can arise during film coating procedure, among which the most important are

1. Tablet Picking

 

Defects in film coating: Tablet Picking

Tablet picking results when two adjacent tablets stick together and subsequently break apart (as a result of the constant motion within the coating equipment) leaving defects in the surface of the coating where pieces of coating have been removed. Depending on whether the defect occurs early or late in the coating process, the affected area may be partially obscured as coating proceeds.

Picking is primarily an over wetting issue and it occurs when the fluid delivery rate exceeds the drying capacity of the process. This process-related problem may be resolved by reducing liquid application rate or increasing drying air temperature and air volume.

Other possible cause of picking may include inadequate atomization, poor product movement or poor distribution of spray. These problems can be avoided by increasing the nozzle air pressure (or the atomization air volume), increasing pan speed and optimizing the uniformity of solution delivery through the spray gun respectively. Additional resolution with respect to changing tablet shape may also include increasing face curvatures to minimize points of contact.




2. Orange Peel/ Roughness

defects in film coating: Orange peel (Excessive roughness)

This condition relates to inadequate spreading of coating solution before drying thereby causing a bumpy or orange peel effects on the coating. Process conditions such as low spray rates coupled with excessive drying conditions (high processing temperatures and airflows) and use of excessive atomizing air pressures (for air-spray systems) which accentuate premature drying of the droplets of coating liquid are likely to cause this inherent roughness to become visible. The problem may also be a consequence of spraying coating liquids with excessively high viscosities such that effective atomization is difficult to achieve. Although some degree of roughness is always evident with film-coated tablets, coating process adjustments that might allow this characteristic to be kept to a minimum such that it is not readily visible to the naked eye include:

  • Optimizing spray rate and/or drying air temperatures and volumes to achieve better atomization of the coating liquid and improve drying
  • Thinning of coating solution with additional solvent to reduce viscosity and thus improve atomization
  • Adjusting the speed of the coating pan to reduce dwell time in the spray zone.

Although the adjustments listed above may fall outside compliance with the registered process, they likely should be considered to be part of the original process design process.

3. Tablet Edge Chipping/ Erosion

Defects in film coating: Tablet Edge Chipping

The attritional effects in the typical film-coating process cannot be overemphasized. Because tablet edges are often exposed most to these attritional effects, fracture at this point is not uncommon and results in parts of the tablet surface being chipped and dented. Tablet cores having high friability values, worn or damaged tablet tooling (that produce “flashing” on the tablet edges), minor lamination problems (with the tablet cores) that exacerbate edge erosion problems, brittle film coatings that offer insufficient protection to tablet edges, excessive mechanical stress imparted in the coating process, excessive pan speed and inadequate tablet design (shape) all contribute to this overall problem.

To reduce tablet edge chipping, coating process adjustments that might be considered include:

  • Reformulating tablet core to reduce brittleness and increase robustness.
  • Increasing compaction forces to reduce tablet friability.
  • Refurbishing or replacement of damaged/worn tooling.
  • Eliminating the tendencies for lamination to occur.
  • Selecting coating formulations with increased mechanical strength and/or increased film flexibility.
  • Spraying coating formulations once the required inlet temperature has been reached instead of prewarming the tablets (a process that usually involves some tablet motion without any coating being applied).
  • Reducing pan speed throughout the coating process (or at least until sufficient coating has been applied so that the tablets receive some protection from the applied coating).
  • Selection of different tablet core design/ surface profile.

4. Bridging of Logos (Intagliations)

Defects in film coating: Bridging of Logos (Intagliations)

Logo bridging of pharmaceutical tablets occurs when a component of the internal stress becomes sufficiently high so as to cause partial or complete detachment of the coating from the tablet surface within the region of the logo. As a result of such detachment, the film is able to “shorten” and thus partially relieve the stress within the film. In doing so, legibility of the logo can be significantly reduced. Because the stress increases with increasing coating thickness, logo bridging of pharmaceutical tablets becomes progressively worse as more coating is gradually applied.

Solutions to bridging involve improving film adhesion and/or reducing stress within the film, and usually require some reformation of either the tablet core or the film coating solution. In addition, appropriate design of tablet punches (especially with respect to the logo) may help to alleviate the problem, whereas adjustment of process conditions may also prove beneficial.

5. Cracking of film coatings

Defects in film coating: Cracking of film coatings

Cracking is the term used to describe a condition in which the continuity of the film is disrupted. It occurs when the internal stress (that develops within the film as it dries) exceeds the tensile strength of the film. Cracking of applied film coating can be microscopic or macroscopic in nature. Although such problems may under many circumstances be purely cosmetic, cohesive failure of the coating certainly detracts from many of the functional qualities of the coating. These problems are, of course, totally unacceptable for products where the applied coating is a major factor in modifying drug-release characteristics.

While cohesive failure is often associated with brittleness of the coating, the problem is certainly exacerbated by thermal expansion effects particularly when significant differences exist between the thermal expansion coefficients for the core and coating, respectively. Because of the catastrophic nature of film cracking, the most effective approaches involve designing tablet core formulations that minimize or eliminate the risk of significant expansion behaviour occurring and creating film-coating formulations that are flexible enough to withstand any tablet core expansion that might occur.



6. Film Peeling and Flaking

Defects in film coating: Film Peeling and Flaking

On occasion (particularly during application of aqueous-coating formulations), if cohesive failure (cracking) of the coating occurs, that coating may subsequently peel back from the surface of the substrate. While both cohesive and adhesive failure are implicated here (both phenomena being linked to internal stress), appropriate solutions typically involve addressing the initial cracking problem by increasing the mechanical strength of the coating.

7. Infilling of Logos

Defects in film coating: Infilling of Logos

While visually similar to logo bridging, infilling of logos typically occur during the spray application of aerated aqueous film-coating solutions. Unlike logo bridging, infilling is caused by a buildup of dried coating solution within the logo. This may be as a result of partially spray-dried material gradually building up within the logo or, the buildup of dried foamy material within the logo.

Normally, dried material that is deposited on the tablet surfaces would breakdown as tablets slide over each other but because the intagliation form a protected area, this will not occur for material that resides in the logo. Once the foam/material has accumulated to a level approaching the outer contour of the tablet surface, normal attrition can occur, allowing the structure to be covered with a continuous film.

The general buildup of prematurely dried material can be corrected by optimizing the atomization process to give a more uniform distribution of droplet sizes. Once this has been achieved, further improvement can be achieved by adjusting coating process conditions (from the thermodynamic standpoint to balance spray rates and drying rates) to ensure that most droplets arrive at the tablet surface in a suitably solvated state to facilitate droplet spreading.

In the case in which foamy material tends to build up within the logo, it is interesting to note that the addition of conventional antifoam agents does not decrease the incidence of this defect. However, the addition of alcohol, the use of spray nozzles capable of finer atomization, optimizing the mixing process either by setting mixer height correctly, choosing mixer blade of correct size (about 30% of tank diameter), choosing optimal mixer speed and incorporation powder into water as fast as possible to avoid excessive viscosity build-up before all powder has been wetted out have been found to be effective.

Read Also: Common defects in sugar-coated tablets

8. Tablet Surface Erosion

Defects in film coating: Tablet Surface erosion

This is another mechanical defect that occurs as tablets tumble during the coating process. In addition to unsuitable punch design, core surface erosion can be facilitated by over-wetting (which causes the tablet surface to soften and hence become less resistant to attritional effects), presence of centrally placed logo, insufficient film strength (to provide resistance to edge damage) and too high pan speed.

This problem can be eliminated by simply addressing over-wetting conditions (reducing spray rates, increasing processing temperatures, or both). Additional solutions might include:

  • Reformulating tablet core
  • Increasing compaction forces
  • Optimizing pan speed
  • Changing punch design to reduce curvature on upper and lower faces and
  • Changing logo location from the centre of the tablet faces to the periphery.




9. Tablet Pitting

Defects in film coating: Tablet Pitting

Tablet pitting is the presence of small pits (indentations) in the surface of the coated substrate. This problem is caused when agglomerates of lubricants such as stearic acid and polyethylene glycol melt under the influence of the coating process conditions used. Although this defect does not interrupt the film coat, it does diminish the pharmaceutical elegance of the dosage form.

Tablet pitting can also occur when large particles of super-disintegrant present in the tablet surface on contact with water from the film coating solution being applied swell to an extent at which they become loosened from the tablet surface, again leaving pits in the tablet surface so that, after the coating has been applied, they still remain visible.

In both cases, the remedies are relatively simple and include:

  • optimizing blending process (prior to tabletting) to minimize the chance of producing agglomerates.
  • optimizing coating process conditions to minimize use of excessively high temperatures (the key factor here will be tablet bed temperatures) when low melting point ingredients are used in the tablet core and
  • preventing over-wetting conditions (potentially offset by reducing spray rates and/or increasing process temperatures) when the core contains very hydrophilic materials, especially super-disintegrants.

10. Tablet Breakage

Defects in film coating: Tablet Breakage

This is one of the most troublesome defects caused by mechanical stress, primarily because it cannot be easily resolved by minor adjustment of the coating process. In this type of defect, tablets break apart during loading of coating pans, during the coating process, or during unloading of coating pan.

Tablet breakage is primarily caused by

  • Mechanical deficiencies in the tablet cores (tablets are not robust enough to withstand film coating process)
  • Variations in die fill uniformity during the tabletting process, possibly due to variations in hopper fill.
  • Mishandling of tablets during loading/ emptying of coating pans.
  • Excessive attritional conditions used during application of the applied coating.

Problems of this nature may be alleviated by

  • Improving tablet core robustness, either by addressing the core formulation or examining the tabletting process (slowing down press speeds to increase dwell time, increasing compaction forces, and possible use of precompression).
  • Ensuring that the coating process is optimized with respect to
    1. Spray rate (increased spray rate provides protection for tablets)
    2. Pan loading (underloaded pans potentially create more attritional problems, especially because tablets can strike the exposed edges of baffles)
    3. Pan speed, which can be reduced to minimize mechanical stress

11. Tablet-to-Tablet Colour Variability

Defects in film coating: Tablet-to-Tablet Colour Variability

Tablet-to-tablet colour variability corresponds to inter-tablet variation of coating. Although variation in the amount of coating applied on each tablet within the batch will, on a weight basis, always exist, the challenge is to ensure that enough coating is applied to prevent visible differences in amount of coating applied or even affecting fi­nal product functionality.

Excessive tablet-to-tablet colour variability may be attributed to;

  • Inadequate uniformity of coating distribution
  • Inadequate hiding power

These problems can be solved by

  • Increasing pan speed to increase the number of presentations to the spray zone during the coating process.
  • Increasing the number of spray guns to expand the spray zone and give better surface coverage.
  • Optimizing pan loading to make sure the tablets are tumbling effectively, with no intermittent stalling of the tablet bed, and to ensure that a consistent gun-to-bed distance is maintained.
  • Balancing both spray rates and drying conditions to achieve good coating process efficiency (typically > 90% and ideally > 95%).
  • Reducing coating solids to facilitate more even coating distribution.
  • Increasing the amount of coating applied to allow better and more consistent tablet coverage.
  • Optimizing spray gun setup so that there is no mis-spraying, that all spray guns are spraying at the same rate, and that each is providing the same area of coverage over the tablet bed surface.
  • Selecting a film coating formulation with increased hiding power (lighter colours tend to exhibit better “hiding power” than darker ones).




12. Tablet Twinning

Defects in film coating: Tablet Twinning

This is the term for two tablets that stuck together, usually after becoming aligned along flat surfaces. Twinning of tablets during coating operation is commonly seen with capsule-shaped tablets and may be due to use of excessively tacky coating formulation or poor suspension evaporation.

While there are certain coating process changes that can be made to obviate this problem, including increasing pan speed to reduce the dwell time in the spray zone (thus reducing over-wetting), improving the drying conditions (such as increasing process air temperatures or volumes and/or decreasing spray rates) or expanding the spray zone (either by increasing gun-to-bed difference, pattern air pressure or the number of spray guns) to minimize the risk of localized over-wetting, proactively dealing with the issue during product development provides a more effective solution.

One approach that can be very effective deals with core design. For example, if a capsule-shaped tablet is required, changing from the more traditional design to one in which there is a small degree of curvature on the edges of the tablets can reduce the area of contact between tablets and greatly minimize the risk of twinning.

Additionally, while all fi­lm coatings will develop some degree of adhesiveness during the drying process, not all coating formulations are equal in this regard. For example, fi­lm coatings based on poly (vinyl) alcohol as well as delayed-release coating based on acrylic polymers are well known for their increased tackiness behaviours. Thus, when these kinds of polymers are required, the use of anti-adhesive agents (such as lecithin, talc, glyceryl monostearate, magnesium stearate) in the coating formulation can be quite effective in reducing their tackiness.

13. Tablet Discolouration

Defects in film coating: Tablet Discolouration

This defect is commonly seen with nutraceutical products and may be expressed in many ways. For example, interaction of ingredients in the core, often in the presence of moisture derived from the coating process, can create dark spots that remain visible through the coating. In a similar vein, migration/ bleeding of ingredients from the tablet core, through the coating can also be a factor. Finally, poor dispersion of pigment ingredients within the coating formulation can also be a source of tablet discolouration; in which case, this must be dealt with at the time of preparation of the coating suspension to make sure pigments are effectively dispersed into the final coating suspension. For coating formulations prepared from powdered premixes made by a third party vendor, the issue of ineffective pigment dispersion must be dealt with by those vendors.

Tablet Discolouration may be solved by minor processing remedies, such as increasing processing temperatures, reducing spray rates, or increasing pan speed to reduce dwell times in the spray zone can reduce over-wetting and thus prevent interaction between tablet core ingredients (such as that between iron salts and ascorbic acid).

Similarly, when ingredients that become liquid and bleed through the coating do so as a result of high processing temperatures, an increase in spray rate and/or reduction in processing temperature can be helpful. However, potential discolouration issues are more effectively dealt with during product development, especially when past experience suggests that this kind of problem is likely to occur in the current product being developed. For example, designing coating formulations (such as high solids coating formulations) that can minimize moisture penetration into the tablet core during application of the coating can effectively reduce or eliminate the problem. Alternatively, if discolouration occurs on storage, use of a moisture barrier coating can also be effective.

14. Scuffing of Film-Coated Tablets

Defects in film coating: Scuffing of film coated tablets

Tablet scuffi­ng involves the generation of grey-to-black marks on the surface of white (or lightly coloured/ pastel) film-coated tablets. Although this problem has been attributed to many causes, it is generally thought to be an abrasion interaction between titanium dioxide in the coating formulation and the surfaces of the stainless steel coating equipment.

Rosoff and Sheen have commented on this phenomenon, linking it to polymorphism that exists with different forms of titanium dioxide. Rowley, on the other hand, confi­rmed that the main issue is related to the level of titanium dioxide used.



While ensuring that the surfaces of the coating equipment are perfectly clean, an approach that can be augmented by pan passivation is a relatively simple approach that can help reduce scuffing problems, a more proactive formulation approach can provide a long-term solution. Reduction in the levels of titanium dioxide used in the coating formulations (as suggested by Ogasawara et al.) can be quite effective; however, this approach will also reduce the opacity of the coating formulation, necessitating the use of higher levels of applied coating to achieve complete tablet core coverage.

Tablet scuffi­ng has, at various times, been associated with the use of coating formulations based on polyvinyl alcohol (PVA). This may be alleviated by using hybrid polymeric film coatings based on combinations of Hydroxypropyl methylcellulose (HPMC) and copovidone.

15. Coated Tablet Dissolution Issues

Defects in film coating: Coated tablet dissolution issues

Generally, unless it is deliberately intended (as in the case of modified release dosage forms), the application of a film coating to pharmaceutical dosage forms should not have any influence on drug release and bioavailability. Dissolution problems occur when there is a statistically significant change in dissolution behaviour after film coating (comparing film-coated tablets to uncoated ones). Although a number of factors may be involved here, the most prominent one is the impact of coating process conditions on tablet core behaviour, rather than the impact of the applied coating itself (through chemical interaction with an ingredient in the core).

For example, for an immediate-release product, ibuprofen tablets (because of the relatively low melting point of this active substance) are well known to exhibit dissolution problems when exposed to high processing temperatures.

In the case of modifi­ed-release dosage forms, coating process conditions can influence the degree to which phase separation can occur with a resulting impact on the size of pores created within the fi­lm structure (and hence drug release) when ethylcellulose is used as primary insoluble polymer and hydroxypropyl cellulose as the water-soluble pore former.

Coated tablet dissolution problem can be solved by

  • Using high solids film-coatings systems (such as Aquarius Preferred HSP) that facilitates the use of lower processing temperatures
  • Adjusting core formulation to improve dissolution behaviour and offset sensitivity to processing conditions
  • Adjusting coating formulation to allow reduction in coating process temperatures.

Recovery of Film-Coated Tablets

Unlike with sugar-coated tablets, film-coated tablets cannot be readily recovered (should a batch be rejected) by simply washing off the coating.

Recovery of film-coated tablets thus typically involves milling of the tablets to produce “granules” that can be introduced (at a predetermined level) into other batches of compression mix (of the same product). Depending on the fracture characteristics of the tablets, and to some extent the adhesion of the coating to the tablet surface, the milling process may cause the coating to flake off so that it can be removed from the tablet core material by sieving.

Usually, however, a portion of the coating will remain in the compression mix. Thus, any rework procedure must be suitably validated so as to ensure that recompressed tablets perform within the specifications of the original product.

Shah, in one of his publications, discussed the use of the Crackulator for recovery of film-coated tablets. Using such equipment, a better separation of tablet and coating fragments was achieved.

Conclusion

Despite advancements and innovations in tablet manufacture, film-coating processes continue to produce many challenges. Assessing the extent of these problems can be difficult because no objective criteria are currently available for this purpose. The development of suitable decision criteria based on objective and quantitative evaluation methods is therefore highly desired. Also, implementation of a proactive approach that acknowledges such problems focuses on problem avoidance during product and process development and provides the most effective means of dealing with a subject that for so long has plagued the production of ­film-coated dosage forms.




References

  • Avis, K., Shukla, A. and Chang, R. (1998). Pharmaceutical Unit Operations: Coating London, Taylor & Francis Group, LLC.
  • Cole, G. (2002). Pharmaceutical Coating Technology. UK, Taylor & Francis Ltd.
  • Felton, L. (2017). Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms (4th). New York: Taylor & Francis Group, LLC.
  • Lieberman, H., Lachman, L. and Schwartz, J. (1990). Pharmaceutical Dosage Forms: Tablets. New York: Marcel Dekker, Inc.
  • Rosoff, M. and Sheen, P. (1983). Pan abrasion and polymorphism of titanium dioxide in coating suspensions. Journal of Pharmaceutical Science, 72(12): 1485.
  • Rowley, F. A. Toward a greater understanding of the scuffi­ng defect observed on ­lm-coated tablets. Tablets & Capsules (April 2012).
  • Ogasawara, Y., Steffenino, R. and Cunningham, C. Scuf­fing measurement methodology and improved fi­lm coating systems. Poster presented at Annual AAPS Convention November 2008.
  • Photo credit: www.filmcoating-troubleshooting.com

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