Pharmaceutical Coating Technology (Part 15)

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Pharmaceutical Coating Technology (Part 15)

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Some common practical questions and suggested answers During the development of coating formulae and processes, common problems tend to recur. This section brings together a collection of typical queries and provides suggested solutions. 1. Question: What major process and formulation parameters do I need to take into account in the change from organic solvent coating to aqueous coating? Answer: Looking first of all at the formulation-based parameters, there is a need to increase the solids loading of the coating suspension to something like 12 %w/w if using a typical HPMC-based formula. Maximizing solids will usefully minimize the water content...

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  1. Page 439 15 Some common practical questions and suggested answers During the development of coating formulae and processes, common problems tend to recur. This section brings together a collection of typical queries and provides suggested solutions. 1. Question: What major process and formulation parameters do I need to take into account in the change from organic solvent coating to aqueous coating? Answer: Looking first of all at the formulation-based parameters, there is a need to increase the solids loading of the coating suspension to something like 12 %w/w if using a typical HPMC-based formula. Maximizing solids will usefully minimize the water content of the suspension but excessively viscous suspension will be difficult to spray. Commonly, organic solvent-based formulae normally contain HPMC viscosity grades of 15 mPa s or even higher. These should be substituted by lower viscosity types such as 5 mPa s. Ethylcellulose is used frequently in organic solvent-based formulae and, of course, will in its simplest form have to be omitted from a totally aqueous formula due to its insolubility. However, use of aqueous dispersions of ethylcellulose (Surelease, Aquacoat) are recommended if a water- insoluble functional coat is required. Regarding the tablet core formula, this needs to be more robust to take into account the rather longer spraying times which may be necessary with water-based spraying. Moisture-sensitive actives are not necessarily a problem in a well-controlled process. The obvious difficulty from a processing point of view is that water, a liquid with a relatively higher latent heat of evaporation, has to be removed from the process. This necessitates higher process temperatures, additional quantities of drying air and generally lower rates of spray application. The initial application of spray demands extra caution as, unlike organic solvent-based spraying,
  2. Page 440 the core cannot be protected by the initial application of a relatively large quantity of spray material. As a consequence of changing from organic solvent-based systems to aqueous-based processing, the following phenomena may also be observed. • A decrease in adhesion of the film for the core. This may be remedied by a formula modification, as described in Chapter 13. • The coated tablets have a distinctly matt appearance compared with organic solvent-based processing. • Shade changes, compared with the organic solvent-based process may be observed even when utilizing the same pigments. 2. Question: Do I need to stir a coating suspension and for how long can I keep it? Answer: A well-milled suspension or a good-quality commercial coating system will need relatively little stirring. However, with formulations containing large quantities of iron oxides and/or talc, stirring should be more or less continuous, especially with talc as a constituent. Cellulosic systems in organic solvents, because of their relatively lower viscosity, will generally settle out more quickly than corresponding aqueous systems. Many aqueous-based coating formulae are susceptible to microbial growth. Large quantities of polymer solution made up for incorporation into batches of final coating suspension will need to be preserved. Commercial coating systems can be constituted in small quantities minimizing waste at the end of the processing period and the consequential need to store and preserve suspension. Unpreserved coating suspensions should be discarded at the end of a working shift and certainly within 12 h of make-up to prevent undue microbial growth. Note that foam generation either from reconstitution of a commercial system or from milling of an ‘in house’ mixture should be minimized. Unfortunately foam on coating suspensions is very stable and difficult to remove. Excessive aeration makes for difficult handling of the suspension. 3. Question: What quality of water should I be using? Answer: Compendial purified water should be used for making coating suspensions of aqueous systems. 4. Question: When do I need to add a plasticizer to a coating formula? Answer: Generally plasticizers are added to coating formulae to make them more universally applicable and to avoid potential coating problems, e.g. cracking, poor adhesion. Some acrylic systems do not need a plasticizer, e.g. NE30D, due to the specialized nature of the polymer used in this latex preparation. For many cellulosic systems, water is a plasticizer but reliance on it is not recommended as it is not permanent within the film and can give rise to problems on storage.
  3. Page 441 5. Question: Are there any detrimental effects caused by using high pigment concentrations? Answer: Excessively high pigment levels can give rise to brittle films which are rather rough in appearance. However, if moisture vapour permeation is a problem then increasing pigment content slightly will usually be advantageous, but excessive quantities may actually increase permeation through destruction of the integrity of the film. It should be noted that the deleterious effect of pigments, can to some extent, be overcome by the use of good-quality small particle size pigments. 6. Question: What is the effect of restrictions in the use of certain organic solvents? Answer: Legislation in many parts of the world, with environmental and worker protection considerations in mind, has the effect of removing certain solvents from use as process solvents. Frequently, these measures involve chlorinated hydrocarbons which are used as cosolvents with alcohols in solubilizing cellulose ethers. Obviously consequential changes for the future would be: • a move to aqueous spraying; • a move to totally enclosed coating processes with solvent recovery system; • a move to polymers with different solubility requirements, e.g. the acrylates. 7. Question: What problems are there for coating moisture-sensitive tablets or tablets containing water-soluble materials? Answer: First, attention should be given to the drying conditions in terms of air temperature and quantity. For aqueous processing both of these should be high. As an example, in a Model 120 Accelacota an inlet temperature of 75–80°C coupled with an air volume of 56–60 m3/min and a low spray rate should be used. With an aqueous system, maximize the solids content to above 12 %w/w if possible so that a low water content is used. The intrinsic permeability of the film should be determined experimentally for a moisture-sensitive core. Adjust pigment and plasticizer levels to minimize moisture vapour transmission. For particularly troublesome cores, consider a change to non-aqueous coating if this is feasible. 8. Question: How do I cure logo bridging on an existing tablet design? Answer: The aim here should be to increase contact between the tablet core and the film; perhaps the most effective way of doing this is to reduce the internal stress in the film itself. The measures detailed in Chapter 13 should be consulted for appropriate remedial action. 9. Question: How can I design the tablet core to avoid logo bridging? Answer: Bridging of logos can be avoided at the punch logo design stage by paying attention to the angles of cut width and finer points of design. When ordering such tooling, it is imperative to inform the tooling manufacturer that
  4. Page 442 the tablets will be film coated. Reputable manufacturers have a great deal of experience to offer in this direction and should always be consulted prior to purchase. 10. Question: How do I assess tablet core quality for film coating? Answer: The fundamental point here is that the tablet core should be designed with film coating in prospect. Marginal core quality in terms of capping incidence will never be improved by film coating; it will only serve to make such deficiencies more obvious. It is difficult to be precise about the normally measured parameters such as diametral crushing strength (DCS) as, to a certain extent, the minimum quantitative values will depend on the coating equipment, its rotational speed or the volume of fluidizing air. As an example, a normal convex circular tablet 10 mm diameter should have a friability of less than 0.5% and a DCS of at least 100–120 N. Smaller diameter tablets can be allowed to have correspondingly lower DCSs. 11. Question: What are the factors to be considered when designing a tablet for coating in terms of size and shape? Answer: In many ways the circular biconvex tablet is an easy shape to film coat. A number of departures from this should be carefully assessed for their coating efficiency: • Flat tablet or parallel sided tablets with a deep edge. These will provide flat adherent surfaces which give rise to ‘multiple’ tablets during the coating process. • Sharp edges or angular tablets. The apexes of these points will be mechanically weak and especially so if slightly overwetted during an aqueous-based process. • Inappropriate shaped logos and logos on the crown of the tablet. The crown of the tablet is the area on the tablet face with the least surface hardness yet is exposed to some of the most intensive abrasive forces in the coating process. Ideally the logo should be around the circumference and not on the crown. It should also be appreciated that the packing density of small tablets is going to be greater than for large tablets. This has the effect that a bed composed of relatively small tablets (and especially pellets) is more resistant to air flow than would occur with large tablets. 12. Question: Can I film coat in a conventional pan? Answer: It must be appreciated that heat and mass transfer in a conventional pan is inherently poor, thus making such equipment a non-ideal choice, especially for aqueous processing. However, processing is possible under the following conditions. First, the cores should be robust as the process will be lengthy compared with that in a more appropriate piece of equipment. Especially in small pans (about 1 m
  5. Page 443 diameter) there is a certain amount of equipment congestion; air spray gun(s), inlet air duct and exhaust ducts have to be fitted into a small space. Spray ‘bounce’ tends to make the process messy but an option during solvent-based spraying (if permissible) is to utilize airless atomizing equipment. Without drying air being able to be drawn completely through the tablet bed, debris from the coating will collect in the pan and may affect the final appearance of the tablets. 13. Question: How many spray-guns do I need and what spray shape should I aim for? Answer: Regarding spray shape, this should be adjusted so that a wide, flattened cone of spray is obtained. However, if very smoothly coated tablets are desired regardless of other factors, then an unmodified cone, as described in Chapter 5, could provide the required results. With larger equipment there is a general feeling that a gain in quality of coating will result if the spray is spread out between a number of guns, as opposed to being confined through one gun. This is practised to counteract the fall-off in intensity of spray from the centre point of the flattened cone to the edge. As a guide, in a Manesty 120 Accelacota use four guns, and in a Model 360 use six guns. The use of a multiple gun set-up does impose the need to balance the liquid spray rate evenly between the guns. Overlap should be minimized as this will give rise to localized overwetting. Obviously, avoid spray reaching parts other than the tablet bed. 14. Question: What is the best location for the spray-gun in the pan? Answer: As a general rule in a side-vented pan, the spray should be aimed at the tablet cascade, about a third of the way down the tablet bed. Absolute gun-to-bed distances will be optimized by trial and error but the configuration suggested by the existing placement of fittings should be regarded as a satisfactory starting point. It should be remembered, especially with large-scale equipment, that increasing the gun-to-bed distance will increase the tendency to spray drying and vice versa on decreasing the distance. This latter action will, of course, lead to a smoother coated surface utilizing the controlled tendency to overwet the tablet bed. 15. Question: What spray-gun type should I use? Answer: One should aim for a purpose-built pharmaceutical spray-gun. These have been made with GMP considerations in mind regarding materials of construction and ease of cleaning. They are generally easier to dismantle than spray-guns from other industries and do not require hand tools for this operation. 16. Question: What are the advantages of using liquid delivery by peristaltic pump over the use of a pressure pot? Answer: Peristaltic pumps give a finer control of liquid flow rate and permit
  6. Page 444 easier stirring of the suspension. They are also, in general, smaller and more self-contained compared with pressurized vessels. 17. Question: What pan speed should I be aiming for? Answer: In some ways pan speed is a compromise between adequate tablet bed mixing and considerations of abrasion of the tablet cores. All manufacturers will give pan speed suggestions for various loadings but occasionally this will have to be modified for a particular need. An example would be a tablet core where edge attrition could be prevented by slowing the pan. This measure can often be helped by increasing spray rate, if that is possible. 18. Question: What are the advantages of an airborne over an airless spray? Answer: Basically an airless spray atomizes a liquid stream by the use of a high hydrostatic pressure through a small orifice nozzle. Its benefits include lack of ‘spray bounce’. However, its relatively high throughput and lack of droplet size control make it generally unsuitable for aqueous-based spraying. It also blocks easily. Here the versatility of the airborne spray, where droplet characteristics are more independent of spray rate considerations, is more appropriate with aqueous spraying. 19. Question: What can I do about poor mixing in my tablet-coating pan? Answer: Apart from suspicions arising from observations of the tablets revolving in a pan, this will be apparent from variable colour coverage if a coloured coating is being used. It will also be apparent from intra-batch variability in performance observed with a functional coating. The tablet bed should flow evenly. Underloading or overloading a pan will cause poor tablet bed rotation and poor mixing. It is also worth while with old equipment to check the manufacturer’s latest recommendation as improvements are often introduced periodically with new models. Some high solids coating compositions are capable of being applied very rapidly, occasionally so quickly as to ‘run ahead’ of the mixing ability of the pan. Under these conditions, when coating times are crucial, the mixing ability of the pan must be upgraded with the assistance of the equipment manufacturer. 20. Question: How do I know that I have achieved the correct rate of application? Answer: Within a given set of drying conditions, the ‘correct’ rate of application will be the one which neither causes overwetting on one hand, nor spray drying on the other. This simplistic picture may be explained further. An excessive spray application rate will be marked by tablet picking and possibly by adherence of tablets to the pan. Spray drying is characterized by an excessively ‘dusty’ coating process where the window or sight glass is obscured by powder deposits. Any horizontal surfaces such as the gun supports will also tend to collect powder under these conditions. 21. Question: Should I expect repeated nozzle blockage with aqueous spray procedures?
  7. Page 445 Answer: Repeated nozzle blockage should not happen during a coating run. The following should be investigated if this occurs: • Coating suspension. Poorly dispersed pigment agglomerates are a common cause. Also the polymer itself may not have been subject to adequate dispersion to fully solubilize it. When using a commercial latex or pseudolatex dispersion, it should be confirmed that coagulation of the coating suspension is not taking place for some reason. Common causes are excessive temperature (both processing and suspension temperature) and unsuitable additives to the formula, causing polymer coagulation. • Process consideration. The atomizing air pressure may be too low. Alternatively, nozzle blockage may be exacerbated by an unnecessarily small nozzle. A diameter of 1 mm is typical for a standard aqueous process. 22. Question: How can film-coated tablets be polished? Answer: It is quite feasible to polish film-coated tablets. However, it is also advisable to consider whether this is really necessary. An aqueously coated tablet may appear matt compared with an organic solvent-coated tablet or even a sugar-coated tablet, but nonetheless the final appearance can be aesthetically pleasing. On the other hand, if ‘house’ requirements or marketing dictate a polished appearance, then there are many possibilities. The following should be taken into consideration: • Acrylic polymer formulations are usually inherently quite shiny but the smoothness of cellulosic systems can be enhanced by a final application of spray suspension without the pigment. • Attention to process conditions is nearly always capable of producing improvements. Spray conditions should be ‘wet’ with a relatively low bed temperature and a higher rate of spray than normal. Extreme caution should be exercised in the initial validation of those conditions as they are conducive to overwetting. • Generally it is possible to use the waxes, polishes and glazes normally utilized for sugar- coated tablets. Nowadays totally aqueous polish mixes are commercially available. Another effective method is to use an aqueous solution of a high molecular weight—PEG, e.g. 20000 grade—sprayed on at the completion of coating. The use of dry carnauba wax added to the completed batch of tablets in a cylindrical pan and rolled for a period until shine develops is also an effective method. Should a lustrous appearance be required, the use of talc in the coating formula should be considered. Sometimes, polishing may be completed in the same pan utilized for coating, providing it is not too contaminated with dried spray. The shape of the tablet bed and the change in noise emitted from the pan can be used as indicators as to when polish and shine has been imparted onto the tablets.
  8. Page 446 23. Question: How can I cure variable dissolution results with controlled release coatings? Answer: Assuming that the dissolution methodology and analytical testing are satisfactory, the process should be examined with regard to the following features: • Is the pan design and product loading appropriate to enable sufficient mixing to take place? • Is the process constant and optimal regarding overwetting or spray drying of coating material? • Has sufficient coating been applied? • In particular with an aqueous dispersed commercial coating for modified release, have the manufacturer’s recommendations regarding processing been followed? The coating formula should be examined to see if it is appropriate for the task, e.g. ethylcellulose will not give an enteric effect. Is the quality of the materials adequate? If changes in dissolution performance of, for instance, modified release coated beads alters on storage then the coating itself is ‘maturing’ or possibly there are interactions between the coat and the core material (see Chapters 2 and 14 for explanation and remedial action). 24. Question: How can I cure metallic marks on white-coated tablets? Answer: This is a problem most often seen with new pans and is especially noticeable with white or pale-coloured tablets. First, the pan should be thoroughly cleaned. If necessary a thin application of spray material to the pan itself will cure the problem. Ensuring that unduly dry spray conditions are not used will also aid the resolution of the problem. 25. Question: How can I optimize the smoothness of a film coating? Answer: Occasionally smoothness and elegance of a film coating is of paramount importance over other factors such as speed of operation and batch throughput. The viscosity of the coating suspension has a major part to play since, generally, smoother coatings result from low-viscosity suspensions/solutions. Chapter 4 should be consulted in detail where recommendations are made on certain types of spray-gun, which can also be a contributing factor to the overall effect. Other process parameters of importance are: • reduction of the gun-to-bed distance • increase in atomizing air pressure • use of an unmodified spray cone. These measures will combine to produce a ‘controlled overwetting’.
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