One of the major steps in formulation development activity is the development of film coating formulation and process. Different dosage forms may need a different kind of coating formulation, technique, and process. Therefore a formulation development scientist has to understand the critical aspects associated with each case. Different dosage forms which can be coated are:
- Tablets,
- Capsules,
- Pellets,
- Granules,
- Particles
- Powder.
All the above-mentioned dosage forms may need a coating for different reasons such as :
- Change in appearance: to impart color for easy identification and brand image building.
- To eliminate dust generation: to reduce handling problems and to reduce dust-induced toxicity.
- Taste masking: mask the bitter or unpleasant taste.
- Odour masking: mask the unpleasant odor of active ingredients like vitamins, antibiotics etc.
- Isolation of incompatible materials: some of the ingredients may be incompatible to each other, and these can be separated by putting a barrier coating in between them.
- Protection from environmental conditions: Some of the ingredients may not be stable in the presence of moisture, light, oxygen etc. The product stability can be improved by coating.
- Change in release characteristics: drug release profile from the dosage form can be tailored by coating techniques for example – delayed-release (by enteric coating), extended-release (by semi-permeable membrane coating or mixing of pellets which are coated to various degrees or with different coating materials).
The application of the coating, which is an additional step in the manufacturing process increases the overall processing time and cost of production. Therefore, the decision regarding the coating technology has to be based on :
- Available facility.
- Overall productivity desired (film coating process is always much faster than sugar coating)
- Environmental and regulatory considerations (all organic solvents are toxic and inflammable)
- The overall cost of the product.
Aqueous Film Coating Technology
As the sugar-coating process is very time-consuming and is dependent on the skills of the coating operator, this technique has been replaced by film-coating technology. This technique was started with the use of organic solvents but now has been replaced with aqueous film coating due to environmental and regulatory considerations. Moreover, the cost of any organic solvent is far more than the cost of purified water.
Therefore, the conversion from organic solvent-based coating to aqueous-based coating makes the coating process more economical, though initially, it may need a little investment to upgrade the coating facility. The need for this upgradation arises due to the need of higher drying capacity (the latent heat of water is 2200 kJ as compared to 550 kJ for methylene chloride which implies that to evaporate water one will need 4 times more energy as compared to organic solvent).
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The problems associated with organic solvent-based film coating and the advantages of aqueous-based systems have long been recognized. Film coating technology has now advanced to the level where the aqueous coating has become a matter of routine rather than an exception. The successful introduction of a wide variety of aqueous-based film-coating products under the brand name DRUGCOAT has resulted in easy conversion from organic solvent-based coatings to aqueous film coating for several companies; many of them still use conventional coating equipment.
Development of Film Coating Formulation
The optimization of film coating formulation may be necessary to improve the adhesion of the coating to the core, to decrease bridging of intagliations, to increase coating hardness or to improve any other property that the formulator deems deficient. The development scientist has to consider three major factors which affect the film quality - the tensile strength of the film coating formulation (mainly dependent on polymer properties), the elasticity of the resultant film (mainly dependent on properties and quantity of plasticizer used) and the film-tablet surface interaction (each and every ingredient used in the coating formulation can affect this interaction and can change the adhesion properties of the film on the tablet surface).
Due to these considerations, it becomes very important to use the most optimized coating formulations in order to get the best results.
Problems in Film Coating
It is very common to see that though one may have decent coating equipment, the final product is still not very satisfactory. One may find various defects in the final products. The basic source of these defects could be any three listed below :
- Defects arise due to defective core formulation or the tablet shape (like high friability, capping, logo or embossing, cratering, and high contact surface area causing twinning.
- Non-optimized coating formulation (problems like logo bridging, poor color dispersion, film cracking, and peeling)
- Non-optimized coating conditions (like pricking & sticking, surface roughness, color variation, spray drying, orange peel, and poor coating efficiency)
The development scientist, therefore, has to critically evaluate the problem and find out the basic reason for the problem, then only the most optimized solution to the problem can be ascertained.
Equipment Requirement for Film Coating
Tablet coating has undergone numerous developments during the last few decades. These changes have resulted in increased interest in equipment designed for film coating from conventional set-up to side-vented pan to fluid-bed coater for different applications. However, the process is complex and requires careful monitoring and control to ensure satisfactory results. The film coating process as such is a combination of four processes going on simultaneously:
- Distribution of coating material on a large number of tablets.
- Mixing of a large batch for the homogeneous result.
- Drying or evaporation of the solvent.
- Solvent vapor removal.
In order to achieve the best results, one has to optimize each process in relation to the other. The major difference between sugar coating and film coating is that generally film coating is a continuous process and is run in almost dry conditions, which implies that the rate of drying has to match the rate of spray. This being the most important aspect of the film coating process ensures a good/poor finish of the final product.
Coating equipment set-up, therefore, has to have provisions to meet these criteria. With careful designing such conditions can be achieved in different set-ups – be it conventional pan/side vented pan or fluid-bed coater.
Solvent to Aqueous Film Coating
These tablets/pills have to be coated for various reasons using a wide variety of materials and processes. The majority of tablets are coated for cosmetic reasons and for the identification of specific brands in the marketplace, however, a number of products are now coated to provide some functional benefits like enteric coating, moisture protective coating, coatings for control release, flavor coating, taste mask coating etc.
Until about 1950, sugar was the first choice as a coating agent for pharmaceutical preparations and much time and effort were spent in perfecting the sugar coating techniques.
Nobody ever was concerned about the problems like material cost, toxic effects due to coating or pollution etc. because the solvent used was always water. However, the sugar coating technique was time-consuming, affecting productivity and the quality of the finished product was dependent on the skills of the operator. Many a time the companies had to reschedule their production plans due to the non-availability of skillful coating operators. These problems led to the development of the film coating technique which was mainly based on solutions of different polymers in various organic solvents. All these solvents are toxic in nature.
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As the level of understanding regarding the toxic effects of these solvents is increasing, industrial hygiene rules and FDA regulations are being tightened the world over, limiting the use of these solvents and the exposure of workers to these solvents. Another area of concern is the cost of these solvents, which can only be expected to increase in the coming times. In today's competitive business environment any cost saved will improve the market viability and success of any product. We are, therefore, left with no other choice but to eliminate the use of organic solvents and start using water as the solvent system for tablet coating. Like any other system, aqueous film coating has some disadvantages.
The main reason for using organic solvents was to avoid the possible decomposition of active ingredients and many other process-related problems such as over-wetting, picking and sticking etc. which may occur with aqueous coating systems. However, research and experience of the industry has indicated that the decomposition of active ingredients and possible coating difficulties are not so serious issues in actual applications and all such problems can be sorted out by scientific evaluation of the reasons for these problems. Most of these problems could be categorized as :
- Material-related problems
- Coating instrument-related problems
- Coating process-related problems
In this article, we will discuss various issues related to Materials used for Aqueous Film Coating.
A large number of problems observed during the conversion from organic solvent-based coating to aqueous film coating are related to the material selected for coating formulation. Some of these problems could be :
- Poor film adhesion
- Poor tablet finish due to high viscosity of coating solution
- The uneven surface of finished product
- Non-uniform color of finished product
- Longer coating cycle time
To understand these coating problems, we will have to understand the properties and role of various materials used in film coating formulations.
Polymers
As the tablet coating technique was changed from sugar coating to film coating, polymers like methylcellulose, hydroxypropyl methylcellulose, ethyl cellulose, etc. became the main coating materials in place of sugar. The higher viscosity grades of HPMC though provided the film with good tensile strength but produce films having poor adhesion with the core surface and very often one can easily peel off the film from the tablet surface. The same HPMC when dissolved in water gives rise to many other problems like -
- high solution viscosity
- water is a poor solvent for HPMC as compared to organic solvents, therefore, solution preparation is difficult
- water has much higher surface tension than organic solvents, and material wetting is difficult resulting in poor film adhesion
- films produced using water as a solvent has poor mechanical properties like low tensile strength, higher modulus of elasticity and low film adhesion.
Therefore, the selection of the correct polymer system is very critical for the success of aqueous coating formulation. By selecting the lower viscosity polymers, the solid content in the coating formulation can be increased which will result in a lesser amount of water required which in turn can increase the coating speed. However, the lower viscosity HPMC produces films with lower tensile strength.
As described earlier the film produced by HPMC using water as solvent system may have poor film adhesion resulting in easy peel-off from the tablet surface. To overcome this problem some formulators have used a combination of HPMC and HPC. HPC provides better film adhesion to the substrate then HPMC, however, other mechanical properties of HPC are not comparable to HPMC, moreover, the cost of HPC is much higher then HPMC and thus makes the formulation economically non-viable. Various other polymers are also used in developing aqueous film coating formulations like Sod. CMC, PVA, PVP, Sod. Alginate, PEG etc. either alone or in combination.
Plasticizers
The next most important component of the coating formulation is the plasticizer. A wide range of plasticizers is available to the formulator such as phthalate esters, phosphate esters, and other esters like citrates, stearates, sebacate, oleate, adipate etc. oils, glycerol, glycols etc.
The important factors to be considered here are :
- The water solubility of the plasticizer: Hydrophobic plasticizers will create problems in solution preparation and can affect the D.T. and dissolution profile of the finished product.
- Water vapor transmission rate through the film: Higher concentration of plasticizer in the film generally tends to increase the water vapor permeability.
Concentration in the coating formulation:
A higher concentration of plasticizer reduces the modulus of elasticity (the desired effect) and thus reduces the possibility of logo bridging but also reduces the tensile strength of the film (undesired effect).
- Film adhesion generally tends to increase with increased concentration of plasticizer.
- A higher concentration of plasticizer can lead to its bleeding (making the tablet surface feel oily).
- In most of cases, the presence of a plasticizer improves the gloss level in the finished product (depending on the quality and concentration of the plasticizer).
- The volatility of the plasticizer: Aqueous coating generally needs higher drying capacity during the coating cycle due to less volatility of water, if the plasticizer is more volatile e.g. propylene glycol, much of the plasticizer may get lost during the coating process.
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Therefore, one needs to strike a balance between the desired and undesired effects of the plasticizer and optimize its concentration in the coating formulation. Many times use of a combination of plasticizers becomes necessary to achieve the most optimum results.
Additives
The properties and composition of other components of the film coating formulation also need to be considered and optimized to get the most desired effects without affecting the quality of the film. Various other components which could be used in coating formulation are -
- Pigments
- Opacifier
- Anti-tacking agent
- Film adhesion enhancer
- Sweeteners
- Flavors
- Anti-foaming agent
The concentration and the properties of each of these excipients can affect the quality of the resulting film, e.g.
- The commonly used colorants in sugar coating are water-soluble dyes. However, the overall colour effect of these dyes depends on the dye concentration at a particular point, the thickness of the film at that point and the residual moisture content in the film at that point. As these parameters can differ from tablet to tablet, the colour difference among various tablets within the same batch may become very visible.
- The opacity of the film depends on the difference between the refractive index of the polymer and other components of the coating formulation. The lake colors used in film coating has a refractive index similar to that of various polymers, thus the opacity of lake colors is very poor.
- The most commonly used anti-caking agent is Talc, which if used in higher concentration tends to settle down from the coating suspension, thus affecting the composition of the suspension during the coating process. Further, it is poor opacifier and tends to produce translucent films.
- As the aqueous film coating needs higher drying capacity, the volatile matter in the flavors used may get lost, changing the nature of the flavor. These volatile matters may also interact with other components of the coating formulation and can affect their properties. One, therefore, needs to use specific flavors and incorporate them in the coating formulation in such a manner so that it does not affect the film quality.
It, therefore, once again becomes a lot of balancing act while developing the optimized coating formulation.
Effect of Residual Moisture
One should keep in mind that water is less volatile than organic solvents, and will require much better drying capacity resulting in higher energy costs for the coating process. However, exceptions do exist in optimized film coating formulations which have a very low affinity for water, and therefore, can be run at lower temperatures, and higher spray rates. Ideal Cures Pvt. Ltd. has developed a few such products (under the DRUGCOAT range of products) which dry faster and the whole coating process can be completed in the same or sometimes a little less time as compared to organic solvent-based coatings.
The use of organic solvents raises the possibility of residual solvent in the finished product which is increasingly becoming a concern to regulatory agencies due to their adverse effects on consumer health.
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