Tài liệu Pharmaceutical Coating Technology (Part 13) docx

Page 363 13 Film coat quality Michael E.Aulton and Andrew M.Twitchell SUMMARY This chapter discusses the desirable properties of polymer film coats with respect to their end usage. The mechanical properties of films were discussed fully in Chapter 12 and so this chapter concentrates on other aspects of film quality such as gloss and roughness, uniformity of film thickness and defects such as cracking, edge splitting, picking, bridging and foam filling of intagliations, etc. The methods of assessing film coat quality by visual observation, light section microscopy, surface profilimetry and scanning electron microscopy are discussed. Other techniques such as dissolution, adhesion measurements and permeability measurements are mentioned briefly. The influence of formulation and process variables on the quality of the resulting film coat is then discussed and advice for the production of a smooth coat is provided. Coating defects are discussed with respect to their cause and suggestions are given for possible methods to reduce their incidence. 13.1 DESIRABLE AND ADVERSE PROPERTIES OF FILM COATS The required properties of a film coat are numerous. The coating may be added to a dosage form for cosmetic, processing or functional drug delivery reasons. A discussion of the reasons for film coating has been given in Chapter 1 , and a further discussion relating to desirable mechanical properties was given in Chapter 12 . In the context of this chapter, it is necessary to clarify the definitions of gloss and roughness, and also to be aware of the correct terminology for the many possible coating defects that might occur. Page 364 Gloss Gloss can be defined as the attribute of the polymer surface which causes it to have a shiny or lustrous appearance. Rowe (1985) determined gloss values of film coats by measuring light reflected at 60° by flat-faced film- coated tablets. He reported that, with organic solutions of HPMC, increased polymer concentration, and thus viscosity, caused a reduction in the gloss of the coat. This was attributed to the increase in the roughness of the coat. It was shown for the coating conditions used in the study that tablet gloss and surface roughness could be related directly by a power-law equation. Roughness The surface roughness of film coats can be quantified by determining various characteristic values, the most commonly used being the arithmetic mean surface roughness (R a ). This may be defined as the arithmetic mean value of the departure of the roughness profile above and below a central reference line over a measured distance. The principle is illustrated in Fig. 13.1 . R a is calculated according to equation (13.1). (13.1) The appearance of a polymer coat is governed to a large extent by its surface roughness. Coats which have smooth surfaces tend to have a glossy appearance, while those with a rough surface appear more matt and may exhibit a surface like that of an orange skin. The surface properties of a coated tablet may therefore be important for aesthetic reasons. Because of the difficulties in achieving glossy film surfaces, gloss solutions are often added after the main coating process (Reiland & Eber, 1986). This inevitably increases batch process time and expense. Knowledge of the factors which would negate use of gloss solutions while still producing an acceptable product in an acceptable time would therefore be beneficial. The measurement of surface roughness may provide information on the behaviour of Fig. 13.1 Diagrammatic representation of the calculation of arithmetic mean roughness. Page 365 atomized film-coating droplets on the substrate surface and thus aid the optimization of the coating process. It may also be used as a quality control tool to monitor film coating at the production scale (Trudelle et al., 1988). Coat surface roughness will be dependent upon the roughness of the substrate, the properties of the coating formulation applied and the coat application conditions. Hansen (1972), King & Thomas (1978) and Rowe (1981a) suggested that the inherent roughness of the original substrate is the most important determinant of the roughness of a coated surface. Film defects The subject of film-coating defects has been discussed by Rowe (1992) in which thoughts and evidence relating to causes and solutions have been gathered together in a comprehensive summary. As part of this work, Rowe makes the point that the careful use of accurate, standardized definitions and terminology is essential. One can only fully endorse this comment. The following summarizes the definitions used by Down (1991) and Rowe (1992). The reader is referred to these articles for further information. Blistering is where the film coat becomes detached locally from the substrate, thus resulting in a blister. Blooming is a dulling of the coating. Blushing is whitish specks or a haziness, observed generally in non-pigmented films. Bridging is a defect in which the film pulls out of the intagliation or monograph in the substrate resulting in the film forming a bridge across the indentation. After intagliation bridging a logo may become virtually unreadable. Bubbling is the occurrence of small air pockets within the film resulting from uncol-lapsed foam bubbles produced during pneumatic atomization. Chipping occurs when the film at the edges of a tablet becomes chipped or dented. Colour variation is self-explanatory. Cracking is the term used to describe the cracking of the film across the crown of a tablet. Cracking is usually easily observable, although the crack(s) may be microscopic. Cratering is the occurrence of volcano-like craters on the film surface. Flaking is the loss of a substantial part of the coating resulting in exposure of the underlying substrate. It usually follows cracking or splitting. Infilling is the presence of solid material (such as spray-dried droplets) in logos, etc. This differs from bridging although the outward appearance may be the same. Mottling is an uneven distribution of the colour of a coat. Orange peel is the phrase used to define a roughened film which has the appearance of the skin of an orange. Peeling is the peeling back from the substrate of an area of film. It is usually associated with splitting at the edge of a tablet. Picking occurs as a result of tablets or multiparticulates temporarily sticking together during coating and then pulling apart. It may result in an area of uncoated surface, although this may be partially obscured as coating proceeds. Page 366 Pinholing is the occurrence of holes within the film coat formed from collapsed foam bubbles. Pitting is where pits occur in the surface of the tablet or pellet core without any visible disruption of the film coating itself. Roughness is due to small vertical irregularities in the surface of the film which affect its smoothness and its visual appearance in terms of glossiness or lustre. Splitting is the cracking of a film around the edges of a tablet. 13.2 METHODS OF ASSESSING FILM COAT QUALITY Four techniques have been employed successfully in the assessment of the quality of film coats: 13.2.1 Visual examination Visual examination will allow a qualitative assessment of the condition of a film coat. Coating defects such as picking, edge splitting, orange peel, bridging of intagliations, etc. (as defined in section 13.1 above) can be recognized. If sufficient of these observations are made, the incidence of defects can be quantified and quoted, as a percentage, for example. 13.2.2 Light-section microscopy The thickness of polymer films applied to tablets or pellets is often determined either by using a micrometer to measure the film thickness after its removal from the substrate, or by extrapolation from knowledge of the amount of polymer applied. The former method is destructive and only measures the thickest parts of the applied film. Adhesion of substrate particles to the film may also lead to artificially high thickness values. With the latter method, accurate values for polymer film density and coating efficiency are required before meaningful thickness determination can be made. Both methods yield a single value for film thickness and give no indication of thickness variation. The light-section microscope A device known as a light-section microscope (Carl Zeiss, Oberkochen, Germany) is available which non-destructively measures the thickness of transparent coatings, allowing the determination of film coat thickness at selected regions on substrate surfaces. It allows analysis of the variation in film thickness and an estimate of surface roughness without physical contact with the tablet or multiparticulate surface (Twitchell et al., 1994). 1. Visual examination by naked eye or with a low - power magnifying glass. 2. Light section microscopy to observe surface roughness and variations in coat thickness. 3. Profilimeter measurements of surface roughness. 4. Scanning electron microscopy. Page 367 The light-section microscope operates on the principle shown diagrammatically in Figs 13.2 and 13.3 . An incandescent lamp of variable brightness illuminates a slit which projects a narrow band of light through an objective ( O 1 ) at an angle of 45° to the plane of the surface being measured. Some of the light is reflected from the surface of the coating; the remainder penetrates the film and is reflected from the surface of the core. In the eyepiece of the microscope at the opposite 45° angle ( O 2 ), the profiles of the coat and core can be seen coincidentally as a series of peaks and troughs after the band of light has been reflected/refracted at the sample, as seen in Fig. 13.4 . A cross-line graticule in the eyepiece can be moved within the field of view by means of a graduated measuring drum. The required distance values can then be read off the drum with a sensitivity of 0.1 µ m over longitudinal or transversal movements of up to 25 mm. For the measurement of film thickness, this technique is restricted therefore to transparent films, however, a certain amount of development work could be performed on unpigmented films, and pigments and opacifiers could be added later. Use of the light-section microscope to determine the thickness of polymer film coats applied to granules has been reported by Turkoglu & Sakr (1992). Analysis of light section microscope images Thickness Due to the refraction of the light as it penetrates the transparent layer, the distance between the light bands, as measured through the eyepiece, does not represent the true thickness of the coating (see Fig. 13.3) and this must be calculated. Fig. 13.2 Light - section microscope: schematic representation of principle. Page 368 Fig. 13.3 Light path through a transparent film during light-section microscopy. Fig. 13.4 Light section microscopy: impression of light lines and graticule in the eyepiece. Page 369 Surface roughness parameters Surface roughness parameters which can be obtained using the light section microscope include: Calculation of R a (the arithmetic mean roughness, see equation (13.1) above) is difficult in light section microscopy and can only be undertaken after a photographic record has been obtained. Visualization of light section microscopy images The diagrams in Fig. 13.5 are representations of light-section microscopy images. They indicate how the roughness of both the coat and the substrate may influence the thickness profile of the coat. Fig. 13.5 (i) indicates that if both the substrate and the coat are smooth, then a film with little variation in thickness will be produced. This combination would represent a desirable situation for film coating since the coat is smooth and of even thickness. Fig. 13.5 (ii) shows how contours of an underlying rough substrate can be overcome if appropriate coating conditions are used. The production of a smooth coat in this case may lead, however, to considerable variation in film thickness, with the thinnest areas of the coat occurring at the peaks of the substrate surface. A similar variation in film thickness may occur if a smooth substrate is coated using conditions which produce a rough coat (Fig. 13.5 (iii)). In this case the thinnest parts of the coat corresponds to the troughs on the coat surface. In examples (ii) and (iii) the variation in film thickness may be important if the film is intended to confer controlled release properties to the substrate tablet or multiparticulate. In the case where a rough coat is applied to a rough substrate (Fig. 13.5 (iv)), the coat generally tends to follow the contours of the substrate, resulting in a coat of relatively even thickness. The examples given in Figs 13.5 (ii) and (iii) are particularly significant when the coat has been added to the substrate to control the rate of drug release from the core. A wide variation in coat thickness is apparent and since the rate of drug release through a water-insoluble polymer coating is directly proportional to its thickness, the consequences are obvious. The ideal scenario is that depicted by Fig. 13.5 (i) where the coat is of very uniform thickness. It cannot be overemphasized here that both a smooth core and a smooth coat are essential requirements. The role of the substrate in film coating is discussed in section 13.3.2 and the effect of formulation and process conditions on the quality of the coat are discussed in sections 13.3.3 and 13.3.4 respectively. 13.2.3 Surface profilimetry Surface roughness can be assessed more accurately by surface profilimetry. Surface R T the distance between the highest peak and deepest valley (µm) R TM the average of five peak-to-valley distances (µm) and R W the average horizontal surface distance between peaks or troughs (µm). Page 370 Fig. 13.5 Light section microscopy images for various substrate and coat combinations. roughness can be quantified, often automatically, in terms of the arithmetic mean surface roughness ( R a ), or other surface roughness parameters. Surface roughness measurements can be made by use of a profilimeter (e.g. a Talysurf 10 surface measuring instrument (Rank Taylor Hobson, Leicester)). This Page 371 instrument assesses surface roughness from the vertical movement of a stylus traversing the surface of a tablet (see Fig. 13.6 ). The vertical movement is converted into an electrical signal which is amplified and processed to give an R a value. Typically, individual coat surface roughness measurements are averaged over a 5 mm traverse length using an 0.8 mm sampling length. R a values up to 5 µm can be obtained. A hard copy trace is also produced. It is important to ensure that the skid and stylus do not damage the surface of the film during the test process (therefore generating erroneous readings). It is recommended that five repeat R a values are determined over the same length of sample. If repeated determinations of R a values over the same area give identical results, this indicates that the skid and stylus are not damaging the film surface during measurement. Values of the arithmetic mean surface roughness ( Ra) have been calculated for a wide range of formulation and process conditions by Twitchell (1990) and Twitchell et al. (1993). The manner in which these conditions influence values of R a are discussed in detail in section 13.3. 13.2.4 Scanning electron microscopy Examination of a film coat surface or section by scanning electron microscopy gives a very clear visualization of coat quality. The spreading and coalescence of individual droplets can be clearly seen. These observations can be correlated with solution viscosity, droplet size and process conditions in order to help explain measured roughness values. These correlations for HPMC E5 films are discussed in section 13.3 . 13.2.5 Dissolution Generally, unless it is deliberately intended, the application of a film coating to a tablet or multiparticulate should not have a negative effect on drug release and bioavailability. However, an important application for coating of pharmaceutical systems with polymers is to control drug release, particularly when using multiparticulate pellets. The achievement of the desired release profile must be confirmed by drug dissolution/release testing. This is a complex issue which is dealt with in many other pharmaceutical texts and thus will not be discussed further here. Fig. 13.6 Principle of surface profilimeter. Page 372 13.2.6 Adhesion measurements A strong adhesive bond between the polymer film and the substrate is essential in film-coating practice. The evaluation of the adhesion of a tablet film to the underlying core is important also from the point of view of understanding certain formulation-related film-coating defects. Fisher & Rowe (1976) and later Porter (1980) have provided details of measuring techniques and adhesion values. The principles, measurement and factors affecting the adhesion between polymer films and substrate have been discussed fully in Chapter 5 and the reader is referred to that chapter for further details. 13.2.7 Permeability measurements A film coat may be required to act as a permeability barrier to gases and vapours, notably water vapour and in some cases atmospheric oxygen. Based on Fick’s Law of Diffusion and Henry’ s law relating the quantity of water vapour dissolving in the polymer to the partial pressure of that vapour, the quantity Q (the amount of water vapour permeating the film of thickness d in time t) can be denoted by: (13.2) where P T is the permeability constant, A the cross-sectional area of the film, and Δp the vapour pressure difference across the film. The evaluation of the permeability of applied films has been studied extensively (see Okhamafe & York, 1983), and the most frequently used apparatus is the ‘permeability cup’ (Fig. 13.7 ). While the permeability cup is very simple to use, it suffers from certain disadvantages in practice, for example the difficulty of obtaining a good seal between the film and the holder. Stagnant layers of water vapour may also act as a permeation barrier. Commercial dynamic methods of measurement are available, and these offer greater accuracy and are much quicker. The permeability of water vapour through a film is susceptible to alteration by both plasticizers (Okhamafe & York, 1983) and pigments (Prater et al., 1982). Oxygen permeability has been studied by Prater et al. (1982). 13.3 THE INFLUENCE OF FORMULATION, ATOMIZATION AND OTHER PROCESS CONDITIONS ON THE QUALITY OF FILM COATS 13.3.1 Introduction The properties of film coats will depend primarily on four factors: the constituents and properties of the substrate, the coating formulation applied, the process conditions under which that film coating is applied and the environment in which the product is subsequently stored. The following sections consider the above four factors. The relevance to changes in the mechanical properties of the film has been discussed in Chapter 12 . [...]... formulation of the coating system also affect this property Coating equipment design A variety of coating pans are commercially available for aqueous film coating These have been reviewed by Pickard & Rees (1974) and Porter (1982) They range from those adapted from traditional sugar -coating pans to those specially Page 383 designed for aqueous film coating (see Chapter 8 for more detail on coating equipment)... the coating of powders, granules and spherical pellets The Accela-Cota is the coating pan most widely used presently within the pharmaceutical industry for aqueous tablet film coating of tablets It has been the subject of the majority of research work investigating the coating process It is available in a range of different sizes, from the Model 10 (24 in (600 mm) pan diameter) which is capable of coating. .. conventional coating pan have been shown to result in differences in the release behaviour of the coated products (Zhang et al., 1991) 13.3.3 The influence of the formulation of the coating solution/suspension The physical properties of aqueous film coating solutions have been discussed in section 4.2 Their influence on the atomized droplet size distribution produced during aqueous film coating is detailed... viscosity of the coating formulation has an influence on both the visual appearance of the tablet and their surface roughness parameters Increases in solution viscosity from 46 to 840 mPa s produced tablets which had progressively rougher and more matt surfaces Similar behaviour was reported by Rowe (1979) for organic film -coating solutions and Reiland & Eber (1986) for aqueous film -coating gloss solutions... contributed to low initial surface roughness values The ease of droplet spreading of low-viscosity coating solutions would also explain why Reiland & Eber (1986) found HPMC E5 solutions of between 1 and 6 %w/v to produce very similar surface roughness values when applied using their model coating system As the coating solution viscosity increases, there is a greater resistance to spreading on the substrate... quality The coating process is complex, involving many interacting variables Although much research has been carried out into how the tablet or multiparticulate formulation and constituents of the coating solution influence the film properties, there have been few extensive studies of the role of process conditions in determining the appearance and behaviour of the coated product Although, in film coating, ... be equally applicable to multiparticulate systems Of particular importance when coating multiparticulates is the geometry (size and shape) of the substrate For a given substrate formulation, varying the size of the substrate can affect dramatically the surface area to be covered by the coating, resulting in a variation in coating thickness for a fixed weight gain This is particularly important for controlled... the coating solvent Rowe & Forse (1974) showed that for 6.5 and 10 mm biconvex tablets coated in a 24 in (600 mm) Accela-Cota, the proportion of tablets failing a film continuity test increased as the tablet diameter increased This was attributed to the greater momentum of the larger tablets as they struck the coating pan, resulting in greater attrition forces Leaver et al (1985) showed that when coating. .. manufacture, up to models capable of coating around 700 kg of tablet cores It is envisaged that differences in coating pan design and, consequently, the way in which the films are formed, could lead to the production of coats which exhibit different properties Little reference to this is available in the literature Stafford & Lenkeit (1984) demonstrated that some coating formulations based on HPMC which... formulations based on HPMC which could be coated in an Accela-Cota, could also be coated successfully in a Pellegrini sugar -coating pan with a dip sword, or in a modified conventional sugar -coating pan Other formulations needed further modification to produce a suitable product in the alternative coating pans The design and setting of the spray gun, which are also extremely important, are discussed separately . numerous. The coating may be added to a dosage form for cosmetic, processing or functional drug delivery reasons. A discussion of the reasons for film coating. mean roughness. Page 365 atomized film -coating droplets on the substrate surface and thus aid the optimization of the coating process. It may also be used