Film coating of pharmaceutical dosage forms

Tablet Coating Process: Film Coating

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Film coating is a contemporary and widely used process for coating oral solid dosage forms in the pharmaceutical industry. It is a process that draws on technologies associated with polymer chemistry, industrial adhesives and paints, and chemical engineering.

The process of film coating involves the deposition of a thin, but uniform polymer-based formulations onto the surface of solid dosage forms such as tablets, capsules, powders, granules, or pallets under conditions that permit:

  1. Balance between, and control of, the coating liquid delivery rate and drying process
  2. Uniform distribution of the coating materials across the surface of the product being coated
  3. Optimization of both visual and functional quality of the final coated product.

The function of the coating may be to improve esthetics, mask unpleasant taste and odour, separate incompatible materials, or modify drug release profile.

The film coating process of today was introduced in the early 1950s as an improvement on the traditional sugar-coating process. The process has proved successful as a result of the many advantages offered, including but not limited to:

  1. Substantial reduction in quantity of coating applied
  2. Minimal weight increase
  3. Increased process efficiency and output
  4. Significant reduction in processing times
  5. Increased flexibility in formulations as a result of the availability of suitable film forming polymers.

In spite of these advantages, there are still some areas of concern in the film coating processes and operations. These concerns arise from the fact that most solvents used in film coating formulation can cause health and environmental hazards. Fortunately, significant advancement in process technology and equipment design, have facilitated the introduction of aqueous-based coating formulations. The result is that less volatile, and safer, solvents such as water can be easily accommodated by the process.

Description of film-coating process

Film coating involves the deposition of a thin layer of film-forming polymeric onto a product substrate. The process can be carried out using conventional panning equipment but nowadays more sophisticated equipment is used to achieve efficient drying, high degree of automation and coating time.

The coating formulation contains a polymer solubilized in a suitable solvent together with other additives like plasticizers and pigments. This solution is sprayed onto a rotating or fluidized tablet bed. The drying conditions cause removal of the solvent, leaving a thin deposit of coating material around each tablet core.

Film coating process: Steps involved in film coating

Schematic representation of the film-coating process

Ideal characteristics of film coated tablets

  • Film-coated tablets should have even coverage with uniform colour coverage across the surface of each dosage unit within a batch, and from batch to batch.
  • Film-coated tablets must be free from defects which affect functionality and stability of the finished product.
  • Film-coated tablets must be compliant with finished product specifications and any relevant compendial requirements.




Types/ classification of film coatings

Film coatings may be classified in a number of ways but it is a common practice to do so in terms of drug delivery system.  Hence film coatings may be classified as either immediate-release film coatings or modified-release film coatings.

Immediate-release film coatings

Immediate-release film coatings also known as non-functional or conventional film coatings are typically reserved for situations in which it is necessary to improve product appearance, ease of swallowing, product stability, and for taste masking. The coatings have no measurable effect on biopharmaceutical properties of the coated dosage forms.

Modified-release film coatings

Modified-release (or functional) film coatings are used when drug release characteristics need to be modified. Modified-release film coatings may be further categorized as either delayed-release (e.g. gastro-resistant/ enteric coating) or extended-release coatings.

Film coating process: Types of film coating

Types of film coating

Raw materials used in film coating formulations

A typical film-coating formulation contains the following materials:

  1. Polymer
  2. Plasticizer
  3. Colourants
  4. Solvent/ Vehicle

Polymers

Polymers are substances whose molecules have high molar masses and are composed of many repeated subunits. They are formed by chemical reactions in which a large number of molecules called monomers are joined sequentially, forming a chain.

In the majority of film-coating formulations, the polymer is the major component in the coating solution. Consequently, this material will have the greatest impact on the final properties of the coating. Some of the key attributes that the film-coating polymer must possess include:

  1. Solubility in a wide range of solvent systems
  2. Solubility requirement for the intended use e.g. free water-solubility, slow water solubility or pH -dependent solubility
  3. Stability against light, oxygen, moisture, heat and the substrate being coated
  4. Continuous film formation capability with adequate mechanical properties
  5. High compatibility with other film-coating additives and the tablet being coated
  6. Low viscosity at the preferred concentration (for adequate atomization)
  7. Nontoxic with no pharmacological activity
  8. Capacity to produce an elegant looking product even in the presence of additives




Polymers used in film coating fall into the following categories.

  1. Cellulose ethersg., Hydroxy Propyl Methyl Cellulose (HPMC), Hydroxy Propyl Cellulose (HPC), Ethyl Cellulose (EC), Methyl Cellulose
  2. Vinyl polymers g., polyvinyl pyrrolidone
  3. Glycols g., high molecular weight polyethylene glycol
  4. Acrylic acid polymers g., Eudragits

Polymers for immediate-release film coating formulations

Common Polymers Used in immediate-release film Coating Formulations

Polymers for enteric film coating formulation

Common Polymers Used in Enteric Coating Formulations

Polymers for Sustained (controlled)-release film coating formulation

Common Polymers Used in Sustained-Release Film Coating Formulations

Plasticizers

Plasticizers are relatively low molecular weight materials which are added to film-coating formulations to modify the physical properties of polymers. This is necessary because most acceptable film-coating polymers are essentially amorphous, and as such, exhibit a reasonably well-defined glass transition temperature, Tg (a fundamental characteristic of polymers that has a profound effect on polymer properties that can also influence film formation, especially when using aqueous polymer dispersions).



Plasticizers act by weakening intermolecular attraction between polymer chains and facilitating coalescence of discrete polymer spheres of aqueous dispersed systems during film formation. This reaction results in increased film flexibility and reduced residual stresses within the coating as it shrinks around the core during drying.

Examples of plasticizers commonly used in film coating processes include:

  1. Polyols, such as glycerol (glycerin), polyethylene glycols (PEG 200 – 6000 grades) and propylene glycol.
  2. Organic esters, such as Diethyl phthalate (DEP), Dibutyl phthalate (DBP), Dibutyl sebacate (DBS), Triethyl citrate (TEC), Acetyltriethyl citrate (ATEC), Acetyltributyl citrate (ATBC), Tributyl citrate (TBC), and Triacetin (glyceryl triacetate; TA).
  3. Oils/ glycerides, such as fractionated coconut oil, castor oil, and distilled acetylated monoglycerides (AMG).

Film coating process: Common Effects of Plasticizers on the Properties of Film Coatings

Summary of Common Effects of Plasticizers on the Properties of Film Coatings

Colourants

Colourants are included in many film-coating formulations to:

  1. Improve product appearance and enable product identification
  2. Modify the gas permeability of a film
  3. Decrease the risk of counterfeiting the product
  4. Protect the active ingredient against light by optimizing the opacifying properties of pigments.

 

Examples of colourants used in film coating

Common Types of Colourant Used in Film-Coating Formulations

While it is possible to use either water-soluble colourants (known as dyes) or water-insoluble colourants (known as pigments), the water-insoluble colourants are preferred in film-coating formulations based on the fact that they:

  1. Exhibit better light stability
  2. Provide better opacity and covering power
  3. Provide a means of optimizing moisture barrier properties of the applied film coatings
  4. Do not suffer from the disadvantageous phenomenon of mottling (caused by solute migration) that can be observed with water-soluble colourants.

As with sugar coating colours, film-coating colourants must comply with regulations promulgated by the national legislation of the country where the products are to be marketed.

Film coating process: Effects of Pigments on the Properties of Film Coatings

Effects of Pigments on the Properties of Film Coatings




Solvents/ Vehicles

Solvents are used to dissolve or disperse coating materials and convey them to the surface of the tablet core. Initially, film-coating processes were very much dependent on the use of organic solvents in order to achieve the rapid drying characteristics demanded by the process. Unfortunately, concerns with operator’s safety, environmental, and cost-related issues have provided the momentum for the current utilization of aqueous-based film coating as the preferred option. However, the use of solvents has continued, especially when:

  1. The coating process will not accommodate the use of water (i.e., drying is poor);
  2. The adhesion achieved with aqueous systems is unacceptable;
  3. Certain critical ingredients (e.g., polymer) are neither water-soluble nor available as a latex system; and
  4. Exposure to an aqueous process would cause stability problems for the product being coated.

 

Examples of solvents used in film coating formulation

Common solvents used in film coating

Miscellaneous coating solution component

While polymers, plasticizers, colourants, and solvents constitute the major ingredients in film-coating formulations, other materials might be used occasionally in low concentrations for specific formulations.

Flavours and sweeteners may be added to mask unpleasant odour of some drugs or to make them more palatable.

Surfactants or dissolution enhancers such as polyoxyethylene sorbitan derivatives may be added to

  1. Emulsify water-insoluble plasticizers
  2. Improve substrate wettability and enhance spreadability of the film during application
  3. Stabilize suspensions

Additionally, some film coatings may also contain preservative/ antimicrobials (e.g., carbamates, alkylisothiazloinone, benzothiazoles etc.), adhesion enhancers (such as polydextrose, maltodextrin, and lactose), antifoaming agents (e.g., dimethylpolysiloxane), antioxidants (e.g., oximes, phenols etc.), pore – forming agents (e.g., sucrose or sodium chloride with ethylcellulose-coated salicylic acid tablets) and waxes. In rare instances, the film coat itself may contain active drug substance.

All ingredients used in film-coating formulations must comply with the relevant regulatory and pharmacopoeial requirements current in the intended marketing area.

Equipment used in film coating

Coating equipment used for film coating process can be broadly classified into three general categories: conventional/ standard coating pans, perforated coating pans and fluidized bed equipment.

Conventional coating pans

The conventional coating pan system consists of a spherical, hexagonal. or pear-shaped pan that rotates on an inclined axis. The rotational movement of the pan causes the substrates to tumble and make multiple passes through the spray application zone. Heat is blown across the surface of the of the tumbling tablets and exhaust air is withdrawn.

Coating pan

Conventional coating pan

The use of conventional coating pan in film coating processes is faced with three major drawbacks;

  1. Low drying efficiency since much of the drying takes place on the surface of the bed of material being coated.
  2. Poor mixing efficiency that results in dead spots (regions of low product movement) in the product bed.
  3. Health hazards for the operator and increased risk of explosion in the case of organic solvent-based film coating due to improper balance between inlet and exhaust air which causes solvent vapour to leak into the general coating area.



Since the conventional pan was in common usage at the time film coating was introduced, this type of equipment initially formed the basis for the film-coating process, with lack of drying efficiency being offset by use of highly volatile organic solvents. A number of modifications were made to the design of the hot air handling equipment to accommodate the aqueous process. Typical examples of such modifications include the design of conventional coating pans with

  1. Immersion sword system
  2. Immersion tube system
  3. Baffled pan and diffuser (Pellegrini pan system)

Film coating process: pictures of Immersion sword system, Immersion tube system and Pellegrini pan system

Perforated coating pans

Perforated coating pan consists of a perforated or partially perforated drum that rotates on its horizontal axis in an enclosed housing. The equipment was developed to maximize the interaction between the tablet bed and the drying air, which it does by drawing the air through the tumbling product bed as opposed to supplying air to the bed surface only. This was important to the development of aqueous fi­lm coating due to the relative high latent heat of vaporization of water (539 kcal/kg), which is much greater than that of the then popularly used organic solvents (e.g., 200 kcal/kg for ethanol).

The perforated coating pan has surfaced as the design of choice in most film-coating applications (the major exception being for the film coating of particles such as beads, pellets, and powders unless modifi­ed with a mesh insert). Mixing efficiency is achieved by the use of appropriately designed baffles on the pan surface.

Perforated coating pans come in various designs depending on the vendor, but the intention is to maximize the drying capability of the machine so as to minimize core penetration at high spray rates. Examples of perforated coating pans include:

  1. Accela-cota (Thomas Engineering, USA)
  2. Hi-coater (Freund-Vector Japan and USA)
  3. Driacoater (Driam Metallprodukt GmbH, Germany)
  4. Glatt perforated coating pan (Glatt., Switzerland, Germany and USA)
  5. Huttlin Butterfly Pan, HBP (G S, Italy)
  6. IDA Coating equipment (Dumoulin, France)

Film coating process: picture of Various designs of perforated pans

Various designs of perforated pans

Fluidized bed equipment

The fluidized bed equipment offers an alternative to pan coating and is particularly popular for coating multiparticulate systems. The equipment offers the potential advantage of being able to affect the most efficient drying of any product that is possible in any existing coating equipment.

In a fluid bed system, the objects being coated are suspended in an upward stream of air, maximizing the surface available for coating. The coating is applied by an atomizer, and this is dried by the fluidizing air.

Film coating can be applied to the fluidized material by a variety of techniques – top spray, bottom spray and tangential spray. The selection of a particular technique is often determined by the nature and intended functionality of the coating applied; for example

  1. Top spray (granulation or conventional mode) is used predominately for taste and odour masking purposes, where drug release rates are not critical since films produced by this method are not uniform in thickness. Additionally, it is suitable for the application of hot-melt coatings.
  2. Bottom spray (Wurster) is preferred for the application of rate-controlling polymers to a wide variety of multiparticulates. The process is also suitable for drug layering when the drug dose is in the low-to-medium range.
  3. Tangential spray (rotary granulator) is suitable for the application of modified-release film coatings to a wide range of multiparticulate products. The process is ideal for drug layering when the dose is medium to high. It is also useful as a spheronizing process for producing spheroidal pellets from powders.

Film coating process: diagrams for three basic processes used for fluid-bed film coating

Schematic diagrams for three basic processes used for fluid-bed film coating

 

Film coating process: Comparison of three fluid bed coating systems : top spray, bottom spray and tangential spray

Comparison of three fluid bed coating systems




Spray Application System

While sugar coasting operations can be accomplished using manual ladling procedures, success of the film coating process rests on the availability of coating equipment with spray atomization system which allows coating liquids to be applied in a much more controlled and reproducible manner. There are basically two types of spray-atomization systems available;

a. Airless (Hydraulic) spray system

In this type of system, the coating solution is pumped at high pressure (250 – 3000 psig) through a spray nozzle with a small orifice. Atomization of the liquid occurs as it expands rapidly on emerging from the nozzle. Because of high delivery rates, this system is typically used in large-scale film-coating operations where organic-solvent-based coating liquids are to be applied. The degree of atomization achieved by this system depends on:

  1. Fluid pressure
  2. Orifice size
  3. Viscosity of coating solution

b. Air-spray system

Here, the coating solution is pumped, under little or no pressure, to the nozzle and is subsequently atomized by means of a blast of compressed air that makes contact with the stream of liquid as it passes from the nozzle aperture. This system is typically more effective in small-scale coating processes and all those involving aqueous-film coating operations. The major drawback of this system is that the atomizing air can give rise to premature spray drying of solution droplets resulting in non-glossy porous film being formed. The degree of atomization achieved by this system depends on:

  1. Fluid pressure
  2. Fluid cap orifice
  3. Viscosity of coating solution
  4. Air pressure
  5. Air cap design

The choice of spray application system for a coating process depends on coating solution formula and on the process developed for a particular product.

picture of Spray application systems

Spray application systems

Common Defects in Film Coating

Coated solids are generally evaluated visually to detect defects in the film. Some defects may be aesthetic in nature, while others are more serious and may compromise the functionality of the coat. Manipulating processing conditions, adjusting the coating formulation, or reformulating the substrate may resolve the problems. Some common problems encountered in film coating include:

  1. Picking – Isolated areas of film pulled away from surface when the tablets stick together and then part.
  2. Orange peel/ Roughness – Film surface rough and nonglossy, like skin of orange.
  3. Bridging of logo – Film pulls out of intagliation or monogram, forming a bridge across the edges of the mark.
  4. Chipping – Film becomes chipped and dented, usually at the edges of the tablet.
  5. Cracking of film coating – Film cracks across the crown of the tablet.
  6. Film peeling and flaking – Film peels back from edge, exposing tablet surface.
  7. Infilling of logo – Intagliation (logos, monograms) filled by solidified foam rendering it indistinct and illegible.
  8. Tablet surface erosion – Tablet surface soften and become less resistant to attritional effects (Tablets exhibit high level of friability).
  9. Tablet pitting – Pits in surface of tablet core without disruption of the film coating.
  10. Tablet breakage – Tablets break apart.
  11. Tablet-to-Tablet Colour Variability – Inter-tablet variation in colour.
  12. Tablet Twinning – Two or more of the tablet cores are stuck together.
  13. Tablet discolouration – Dark spots that remain visible through the coating (often seen with multivitamin tablets)
  14. Scuffing – generation of gray-to-black marks on the surfaces of white (or lightly coloured) fi­lm-coated tablets.
  15. Coated tablet dissolution issue – statistically significant change in dissolution behaviour after film coating (comparing film-coated tablets to uncoated ones).




Differences between film coating and sugar coating

differnces between film coating and sugar coating

Examples of film-coated tablets

  • Curefenac 100 – Diclofenac potassium USP (Unicure Pharmaceutical Limited)
  • Valsartan 320 mg (Actavis UK Ltd)
  • Ranitidine 300 mg (Accord Healthcare Limited)
  • Ondansetron 8 mg (Aurobindo Pharma – Milpharm Ltd.)
  • Aindeem – Finasteride 1 mg (Accord UK Ltd.)
  • Magnezinc – Zinc 30 mg (as zinc sulfate monohydrate) and Magnesium 300 mg (Berko Pharmaceuticals)
  • Nurofen Cold and Flu – Ibuprofen 200 mg and Pseudoephedrine 5mg (Reckitt Benckiser)
  • Atenolol 100 mg (Teva)
  • Accord Clarithromycin 500 mg – (Accord Healthcare Limited)
  • Trifene 200 – Ibuprofen 200 mg (Grupo Medinfar)
  • Alrinast 5 mg – Desloratadine 5 mg (Bristol Laboratories Ltd)
  • Desogestrel 75 mcg (Accord UK Ltd.)
  • Easofen 200 mg – Ibuprofen 200 mg (Clonmel Healthcare Ltd)
  • Berocca Performance – Vitamin and mineral supplement (Bayer Healthcare Pharmaceutical Inc)
  • Theospirex Retard 150 mg – Theophylline 150mg (Gebro Pharma)
  • Leptica 1000mg – Levetriacetam 1000 mg (Ilko Pharmaceuticals)
  • Doxepin-neuraxpharm 100 – Doxepin 100 mg (Neurapharm Arzneimittel GmbH)
  • Motilium 10mg – Domperidone 10mg (Zentiva)
  • Rowalief 500 mg – Paracetamol 500mg (Rowa Pharmaceuticals Ltd)
  • Risedronate Sodium 35 mg (Sandoz Limited)
  • Algopet 100 mg – Flurbiprofen 100 mg (Ilko Pharmaceuticals)
  • Harvoni 90 mg/ 400mg – Ledipasvir 90 mg/ Sofosbuvir 400 mg (Gilead Sciences)
  • Ranix 300 – Ranitidine 300 mg (Jadran-galenski laboratorij)
  • Cenipil – Donezepil 10mg (Target Pharma Healthcare)
  • Aclosh 100 – Aceclofenac 100mg (Manish Pharma Lab)

Advantages of film coating over sugar coating

  1. The film process is simpler and, therefore, easier to automate
  2. Enhances the elegance and glossy appearance of coated tablets.
  3. Minimal weight increase (typically 2–3% of tablet core weight) as opposed to more than 50% with sugarcoating.
  4. Increased flexibility in formulations as a result of the availability of a wide range of coating materials and systems.
  5. Moisture involvement can be avoided (if absolutely necessary) by using nonaqueous solvents.
  6. Significant reduction in processing times with increased process efficiency and output.
  7. Distinctive identification tablet markings are easily obtainable.
  8. Improves mechanical integrity and resistance to destruction by abrasion during transportation.
  9. Ability to be applied to a wide range of pharmaceutical products (e.g., tablets, capsules, granules, nonpareils, powders, drug crystals)

Disadvantages of film coated tablets

  1. Possible explosion as a result of the flammability of some of the organic solvents used as vehicles for the film forming polymers.
  2. Some of the solvents used in film coating processes are toxic and could constitute health hazard to the formulation scientist.
  3. Some of the solvents and polymers used in film coating are relatively expensive.

References

  • Allen L. and Ansel H. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.
  • Aulton, M. and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
  • Avis, K., Shukla, A. 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. (2012). Remington Essentials of Pharmaceutics. UK: Pharmaceutical press.
  • Felton, L. (2017). Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms (4th). New York: Taylor & Francis Group, LLC.
  • Film Coating Technology: Past, Present and Future. Available from: https://www.researchgate.net/publication/263725433_Film_Coating_Technology_Past_Present_and_Future [accessed Dec 20 2018].
  • Lieberman, H., Lachman, L. and Schwartz, J. (1990). Pharmaceutical Dosage Forms: Tablets. New York: Marcel Dekker, Inc.
  • Ofoefule, S. (2002). Textbook of Pharmaceutical Technology and Industrial Pharmacy. Nigeria: Samakin (Nig.) Enterprise.
  • Qui, Y., Chen, Y., Zhang, G., Yu, L. and Mantri, R. (2017). Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice (2nd). United Kingdom: Elsevier Inc.
  • Venkateswara Reddy, B, Navaneetha, K., and Rashmitha Reddy, B. (2013). Tablet Coating Industry Point View- A Comprehensive Review. International Journal of Pharmacy and Biological Science, 3(1): 248 – 261.
  • Wen, H. and Park, K. (2010). Oral Controlled Release Formulation Design and Drug Delivery: Theory to Practice. New Jersey: John Wiley & Sons, Inc.

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