Coating of pharmaceutical products is a process which is more than 300 year old. Earlier, medicated pills were coated with ingredients like gelatin, sugar, talc etc. along with some very basic colours like charcoal, gold, silver etc. These kinds of products continued to be produced till about mid 19th century when the process of compressed tablets became common. Coating process was then developed for such compressed tablets which was nothing but what is commonly known as sugar coating.
Tablet film coating is now a well established process and almost everywhere tablet coating has been converted from sugar coating to film coating for obvious reasons of productivity and much less dependence on the manual skills of coating operators. However, the film coating has a number of constraints while manufacturing. The formulation development scientist has to not only optimize the coating formulation and process but also has to design the tablet core formulation differently in order to accommodate the additional stress and specific requirements of film coating process.
The requirements of the aqueous film coating process gives additional stress on the coating process and the tablet core as compared to organic solvent based film coating process. While many of these problems caused by these additional stresses can be reduced by the careful control of the coating process and the use of optimized coating material, the core tablet (formulation and characteristics) also play a very important role in obtaining the best results. Many times the core characteristics may be such that that even after best possible controls of coating material and process conditions, the end results may not be acceptable.
Sometimes formulation development scientist do not pay enough attention to various core properties in terms of particle size and porosity of the granules, compressibility index of granule mix, physical strength of the compressed tablets, interaction with colours and other coating ingredients etc. and feel that all such issues will be taken care by the film coating material manufacturer. However, in practice it may not happen due to various factors. Therefore, it is important that tablet core characteristics should be considered in the development of the dosage form that will be film coated.
Tablet formulation design :
With all these constraints however, the benefits of film coating which include providing a unique dosage identity, enhancing appearance, masking bitter taste and improving product stability; more than justify the exposure of tablets to the rigours of film coating process. The tablets which need to be film coated should be robust enough to withstand the additional stress of film coating process. The tablets must therefore, be formulated and designed using more stringent criteria than for uncoated tablets.
Among the various factors which can affect the core tablet characteristics, following ones have very significant impact and therefore, must be carefully optimized.
Granule characteristics
The granulation optimization and the resulting granule characteristics play a very major role in the success of film coating process and the finish of the final product.
● API characteristics: The whole development exercise for tablet core starts with the proper selection of API characteristics like particle size, crystal shape, bulk density, solubility etc. Though in most of the cases, people work with whatever kind of API is available , in case of tailor designing of core characteristics, the properties of API may need certain modifications like reduction of particle size by milling, increasing the solubility by treating the API with some surface active agent etc. Such treatment given to API may also change the properties like compressibility which in turn can affect granule characteristics and the physical properties of the compressed tablets and thus affecting the film coating process.
● Selection of excipients :The next important point is the careful selection of excipients like dilutents, binder and intragranular disintegrant. It is a known fact that starch though works as an excellent dilutent and disintegrant, but very high concentration of it makes the granules very fragile, hence the resulting compressed tablet may be very weak and makes it difficult to film coat by aqueous process. Similarly, another excellent dilutent is MCC, but during wet granulation, if the dough is over-kneaded, then it results in quite spherical and free flowing granules which are difficult to compress into tablets with good breaking strength even with high compression force as the granules loose the compressibility. These kinds of tablets easily crumble in the coating pan and could be a nightmare for film coating operator.
● Multicomponent tablets :In multicomponent tablets like multivitamin with minerals, one may carry out the granulation in different stages like one granulation for vitamins and other for minerals which are than mixed together during lubrication stage. Such granules when compressed into tablets cause a different kind of problem during film coating especially during aqueous film coating, that the core surface is smooth initially but the film coated tablet surface may be with lots of pin-holes (the problem is also known as cratering). This is due to the fact that mineral granules have much higher thermal expansion than vitamin granules. Therefore, these granules when heated during coating process expand and may fall apart from the tablet surface giving rise to the pin-hole phenomenon.
● Unoptimized granulation :Yet another big problem observed during film coating is capping which is again due to unoptimized granulation process. This phenomenon is generally observed with crystalline APIs like Paracetamol, Metronidazole etc. Due to crystalline nature, the granules do not bind so strongly during compression giving rise to capping when the tablets are subjected to high mechanical and thermal stress during coating process. Such problem can be reduced or eliminated by using high concentration of more compressible excipients like MCC or by reducing the particle size of the API or by increasing the binder concentration.
Tablet hardness :
This is a factor which is easily measurable and to some extent controllable, however, it largely depends on the optimization of granule characteristics. In order to withstand the high mechanical stress during film coating process, core should be strong enough (tablet core continuously hit each other as well as the metallic surface of the coating pan).
This is not a major constraint during sugar coating process due to the fact that before sugar coating a barrier coat of shellac solution is generally applied which provides enough mechanical strength to the core tablet. However, any such coat is not utilized before film coating.
Friability :
More than hardness, friability is a critical parameter for the compressed tablets which are to be coated. For an uncoated tablet, a friability limit of NMT 1.0% w/w is generally considered reasonable, however, for film coating any value of more than 0.5% w/w is generally very high. More acceptable limit of friability is NMT 0.2% w/w. The reason being that highly friable tablets will result in rough surface after film coating either due to surface or edge erosion or more importantly the powder generated by such friable tablets getting re-deposited on the tablet surface during coating process. This kind of re-deposition could be disastrous while using non-perforated coating pan as there is no escape for the powder (in case of perforated pan, part of the powder may go into the exhaust through perforation in the pan). One must remember that while friability test is carried out for only four minutes whereas the initial surface coverage during aqueous film coating may take anything from 20 minutes to 60 minutes depending on the spray rate and the mixing capability of the coating machine and during that period there can be lots of surface erosion from the uncovered tablet surface.
Use of lubricants :
While compressing the granules into tablets, certain amount of lubricant like Magnesium Stearate is essential for smooth operation of the compression machine. However, these lubricants may make the tablet surface quite hydrophobic causing poor film adhesion of aqueous film coating. Further, as the surface tension of water is very high, aqueous film coating suspension may not provide enough surface wetting on such hydrophobic surface causing very uneven or patchy coated surface. Hence, one should be careful while adding lubricants like Magnesium Stearate to the granules so as to use just the minimum possible concentration and not to over-lubricate the granules.
Use of super–disintegrants :
Modern day pharmaceutical scientists tend to use a good concentration of super-disintegrants like AcDiSol, Polyplasdone, Sodium Starch Glycolate etc. for the want to achieve the drug release characteristics / dissolution profile etc, however, these disintegrants can create serious problems during aqueous film coating. If the drying capacity during the initial phase of the coating is not good, some amount of moisture absorption may happen as the aqueous film coating suspension wets the tablet surface. This moisture may activate the super-disintegrant and the core surface may start disintegrating in the coating pan causing the surface erosion resulting in very rough tablet surface. One, therefore, has to be very careful regarding the concentration of such disintgrants as well as the initial drying of the film coating.
Presence of logo / break-line :
For easy brand identification of the product in the market place or even to differentiate various products at production floor, it may be advisable to put some logo or break-line on the tablet surface. These logos generally look very good on properly compressed tablets but may be a cause of concern during film coating. Certain very common problems like logo bridging or logo filling will obviously be observed only on the tablets with logo. The depth and calligraphy of logo can play a role in logo filing as described in the adjacent picture.
Further, it is a known fact that the surface hardness for a biconcave tablet is maximum at the edges but lowest at the crown of the tablet, implying that the centre of the tablet to be softer than the edges. Therefore, a logo put across the periphery is likely to be more stable than the one put at the centre. Such logo put at the centre is likely to get eroded during film coating process.
The presence of break-line can be another serious problem as the large size tablets with lower thickness are likely to break inside the coating machine leading to high level of rejection. In fact any tablet which is to be coated should be dispensed to the patient in the intact form, therefore, there is no scientific justification for break-line on the coated tablets.
These logo or break-line could be disastrous for functional coating (like moisture protective coating, enteric coating or sustain release coating) as the film thickness at the logo or break-line is not the same as on the continuous surface of the tablet. Generally the film thickness at the edge of logo is very low. Therefore, in case of enteric coating, one may have to apply larger quantity of coating on the tablet with logo as compared to the one without logo or break-line. Sometimes when the break-line is very deep, crack in the film may generate inside the break-line causing the failure of enteric properties. This is generally observed during accelerated stability studies on such tablets. Therefore, it is advisable to avoid any kind of logo or break-line for the tablets which need enteric coating.
Tablet shape :
The shape of the tablet may affect overall results as it can have a considerable effect on the tablet hardness, tablet friability, edge erosion (in case of sharp edged tablets), mixing characteristics of the whole lot in the coating machine etc.
The tablets may be compressed using tooling of various geometries, it could be flat shaped, round biconcave (the concavity can be different from shallow concave to standard concave to deep concave or to almost like a ball; depending on the curvature of the punch surface), capsule shaped with flat or round edges, elliptical or oval shaped or with some very specific shaped like heart shaped etc. The round shaped tablets will easily roll inside the coating machine as compared to any other shape resulting in higher probability of uniform coating. However, a very deep concave tablet, though rolls very well but is likely to have the soft centre as the compression force is maximum on the edges and minimum in the centre; will be prone to abrasion at the crown of the tablet. Whereas a flat round tablet will show very poor mixing in the coating machine and higher probability of edge erosion, it will also have the tendency of twinning.
Twinning is a phenomenon often observe during coating and is mainly due to the availability of large flat surface either on top of the tablet (like in flat tablet) or on the side (like in caplet). These flat surface when wetted with the aqueous polymeric solution, tend to stick to another such surface available on another adjacent tablet (most of the polymers used in film coating are like glue and their aqueous solutions does not dry very quickly, hence, are sticky in nature).
By making small change in the curvature of such flat surface, the problem of twinning can be avoided. The caplet shape may also be changed to slightly elliptical one to prevent twinning. Such change in shape (from flat to slightly curved surface) also helps in improving the tablet mixing in the coating machine thereby making the coating process more uniform. One can easily visualize that the similar rounding of the edges will provide better tablet mixing, less probability of edge attrition and may be less friability inside the coating machine. For enteric coated tablet, such rounding of the edges can be useful. The sharp edge tablet may need much higher enteric coating to overcome the film weakness at the edge as compared to round edge tablet (the film thickness and the film strength is always lower at the edges).
Conclusion
The requirements of aqueous film coating place additional stress on the whole process as compared to organic solvent - based coating causing many unforeseen problems. While many of such problems can be reduced by careful selection of the optimized coating formulation and good control on the process parameters, the best results will be obtained by equally careful selection / optimization of core characteristics.
- Suresh Pareek is the managing director & Chetan Rajsharad is the general manager (Technical ) of Ideal Cures Pvt. Ltd