Tài liệu Pharmaceutical Coating Technology (Part 5) ppt

Page 118 5 Surface effects in film coating Michael E.Aulton SUMMARY This chapter will explain the significance of the stages of impingement, wetting, spreading and penetration of atomized droplets at the surface of tablet or multiparticulate cores. It will explain some of the fundamental aspects of solid-liquid interfaces which are important to the process of film coating. This chapter will emphasize the importance of controlling the ‘wetting power’ of the spray and the ‘wettability’ of the substrate, and will explain how this can be achieved by changes in formulation and process parameters. Both surface tension and contact angle are important properties in influencing the wetting of a substrate surface (whether this be tablets, granules or spheronized pellets) by the coating formulation. These properties have been evaluated in coating polymer systems because of their possible relationship with wetting, spreading and subsequent adhesion. These aspects are discussed in detail in this chapter. The chapter also contains a discussion on the adhesion properties of the final dried film coats and some data are presented to illustrate the factors influencing the magnitude of these adhesive forces. 5.1 INTRODUCTION In our deliberations on the process of film coating of pharmaceutical solid dosage forms, one cannot escape a consideration of surface aspects relating to the wetting of granule, pellet or tablet cores by the coating solution and the subsequent adhesion of the dried films. Page 119 This chapter will consider some fundamental aspects of these stages and explain the mechanisms involved in the spreading and wetting of droplets once they hit the substrate. While it is not always necessary to have a firm grasp of these concepts to produce a satisfactory film coat in practice, an awareness and understanding of some of these theories will help to produce much more efficient and elegant films. Film coatings are invariably applied in the pharmaceutical industry by spraying a coating solution or suspension onto the surface of a bed of moving tablet cores or onto fluidized multiparticulates. Hot air is blown through the bed to evaporate the solvent in order to leave a continuous polymer film around the cores. Droplet generation, droplet travel from the gun to the bed, impingement, spreading and coalescence of the droplets at the surface, and subsequent gelation and drying of the film, are all important factors which need to be understood and, where possible, controlled. This chapter will concentrate on those processes which occur at the interface between the droplets of coating liquid and the surface of the substrate cores. It will consider the importance of solution and core properties and process conditions, although the latter will be explained in more detail in other chapters. Once the sprayed droplets of film-coating solution hit the surface of the substrate core, they will (hopefully) adhere to the surface and then wet and spread over the underlying surface. They should then form a strongly adhered, coherent dried film coat. Control over the collision of the droplets with the substrate is primarily a function of apparatus design, and the positioning and settings of the spray-guns. The velocity of the droplets as they hit the cores ensures that they have a momentum. This momentum will provide some of the energy required for spreading. Since momentum is the product of mass and velocity, its value is obviously a function of the size, speed and direction of the droplets at the point of contact. This aspect is also discussed more fully in Chapter 13 in the context of the effects that droplet size, gun-to-bed distance and other processing variables have on the quality of the resulting coat. 5.2 WETTING 5.2.1 Wetting theory First, let us consider briefly the relevant theory relating to wetting. True wetting is defined as the replacement of a solid-air (or more correctly solid-vapour) interface with a solid-liquid interface, i.e. in simple terms, a ‘dry’ surface becomes ‘wet’. During this process individual gas and vapour molecules must be removed from the surface of the solid and replaced by solvent molecules. The relative affinity of these molecules will dictate whether this process is spontaneous or not. It should be appreciated that this process is influenced by the two properties of wetting power and wettability. In the context of film coating, ‘wetting power’ can be defined as the ability of the atomized droplets to wet the substrate and ‘wettability’ can be defined as the ability of the substrate to be wetted by the atomized droplets. Page 120 An appreciation of this subdivision of wetting helps us to appreciate that in practice it is possible to manipulate the interfacial process by adjustment of either (or indeed both) the properties of the droplets, or those of the tablet or multiparticulate cores. 5.2.2 Surface tension Introduction The following discussion attempts to introduce the reader to the concepts of interfacial tensions within the context of film coating. It is not intended to be a full explanation of the science of the subject. The reader is referred to standard physical chemistry texts for a fuller, more fundamental explanation of these principles. All interfaces between various states of matter will have an excess surface free energy. This arises as a result of the unsatisfied molecular or atomic bonds present at a surface of the material, since these particular molecules or atoms are not completely surrounded by other like molecules or atoms. We are all familiar with the concept of liquid surface tension, but from the above description you can appreciate that all surfaces will have this excess free energy (or surface tension). In the context of film coating, we have to consider the following interfaces. Liquid-vapour (LV) interface This will exist between the droplet of coating solution and its surrounding environment. This is often referred to as the liquid-air interface but this is not strictly correct since the air directly at the interface will be saturated with solvent vapour from the droplet. Note also that the same basic principles apply whether or not the liquid in question is water (as in aqueous film coating) or an organic solvent (as used in organic film coating). The symbol for the liquid-vapour interfacial free energy (or surface tension) is γ LV . Its typical SI units are mN/m. Solid-vapour (SV) interface This is the ‘dry’ solid surface. The word ‘dry’ is quoted since the surface will not be free of solvent molecules. There will be an equilibrium between solvent molecules present in the air and those adhered to the solid surface. Thus, again, solid-vapour interface is a more accurate description than solid- air. The corresponding symbol and unit are γ SV and mN/m, respectively. Solid-liquid (SL) interface This is the wetted solid. There will still be a residual surface free energy between the two phases because they are different materials. The magnitude of the SL interfacial free energy is influenced by the properties of both the phases. This is an important point to grasp because it indicates that the process of wetting (i.e. the generation of a SL interface) can be influenced by changes to either the spray or the solid, as was discussed earlier when the terms ‘wetting power’ and ‘wettability’ were introduced. Page 121 The corresponding symbol and unit for SL interfacial free energy are γ SL and mN/m, respectively. Measurement of liquid surface tension The measurement of SL and SV interfacial free energy is extremely difficult to perform and is beyond the scope, not only of this book, but also of most companies involved in film coating. The measurement of LV interfacial free energy (or liquid surface tension as it is commonly called) is relatively easy, however. Furthermore, it is possible to obtain an insight into the γ SL and γ SV values by measurement of the contact angle of a sessile drop of liquid on a horizontal solid surface. This is explained later in section 5.2.3 . There are two simple and commonly used techniques for determining γ SV . These are referred to as the Du Nuoy tensiometer and Wilhelmy plate techniques. The Du Nuoy technique consists of measuring the force (often using a torsion balance) needed to pull a horizontal metal ring free from the surface of a liquid. In the Wilhelmy technique the horizontal ring is replaced by a vertical plate. In both techniques surface tension can be calculated since the experiments measure the downward force on the ring or plate resulting from the excess surface free energy in the surface of the liquid. For further details of these techniques, the reader is referred to textbooks on physical chemistry. Surface activity of HPMC solutions The surface activity of HPMC solutions was discussed in Chapter 4 (section 4.2.3). Data were presented which showed that the addition of HPMC greatly reduced water surface tension at low concentrations, but over those concentrations likely to be used in practice there is little further change in equilibrium liquid surface tension. Surface ageing HPMC E5 solutions at concentrations of approximately 5×10 −3 %w/w or less were found to take a considerable time to reach their equilibrium surface tension values. This time-dependent reduction in surface tension of aqueous HPMC E5 solutions has been studied by Twitchell (1990) and is illustrated in Fig. 5.1 for solution concentrations in the order of 10 −4 %w/w and Fig. 5.2 for more dilute solutions in the order of 10 −5 %w/w. It can be seen that the time taken for the equilibrium surface tension to be reached decreases as the concentration increases. For concentrations below 5×10 −4 %w/w, time periods in excess of 30 minutes were required under the conditions of test. At least 900 minutes was required before the 2×10 −5 %w/w solution attained equilibrium. This phenomenon of time-dependent surface tension is known as surface ageing . This has also been reported for high molecular weight hydroxypropyl cellulose samples at aqueous solution concentrations of 2×10 −5 %w/w and below (Zografi, 1985). Surface ageing occurs since, when a fresh liquid surface is formed (such as in atomization), it will be relatively free of actively adsorbed HPMC molecules. This is Page 122 Fig. 5.1 The relationship between surface tension and time for aqueous HPMC E5 solutions of various concentrations. not, however, the equilibrium state. There will be a gradual diffusion of solute molecules from the bulk of the solution to the droplet surface and orientation of the molecules once at the surface until an equilibrium situation is achieved. The wide distribution of molecular weight fractions in HPMC E5 (Rowe, 1980a; Davies, 1985) is likely to contribute to the time-dependent nature of the surface tension, with the larger molecules diffusing less rapidly and being more sterically hindered. The attainment of the equilibrium surface tension will correspond to that of equilibrium adsorption, this being a dynamic state with molecules continuously leaving and entering the surface layer at the same rate. The time- dependent non-equilibrium surface tension is referred to as the dynamic surface tension. Page 123 Fig. 5.2 The relationship between surface tension and time for aqueous HPMC E5 solutions of various concentrations. Non-ionic surface active agents, into which category HPMC E5 can be classified, tend to exhibit marked surface activity at considerably lower concentrations than ionic ones with identical hydrophobic groups. If the surfactants form micelles, this leads to a subsequent tendency for lower values of the critical micelle concentration. The attainment of equilibrium surface tension values at concentrations below the critical micelle concentration has been found to be considerably slower with nonionic surfactants, and for a specific surfactant to be slower for lower concentrations (Lange, 1971; Wan & Lee, 1974). At concentrations below the point of inflection in the surface tension/concentration curve (see Fig. 4.2 for HPMC), it can be considered that the surface can accommodate all the HPMC molecules in the solution, and Page 124 thus before the equilibrium surface tension is reached these molecules must make their way to the surface. As the solution concentration increases, the molecules which are required to reach the surface have, on average, a shorter distance to travel and thus equilibrium is attained more quickly. HPMC E5 solutions with a concentration greater than approximately 5×10 −3 %w/w attain equilibrium surface tension values sufficiently quickly such that no time-dependent reduction in surface tension can be detected. Surface tensions of atomized droplets The above discussion implied that the surface tension of atomized droplets may not be as expected. Twitchell et al. (1987) took this argument one stage further. Surface tension data measured on the surface of bulk liquid at equilibruim could give a misleading result. As Table 4.2 showed, the surface tension under such conditions changes little over a wide range of concentrations that are likely to be used in practice, with an abrupt rise in surface tension only being significant at concentrations below 2×10 −5 %w/w HPMC. However, there are two factors which are very different in film-coating atomization compared to the experimental situation. First, there is the sudden generation of a very large area of fresh surface (i.e. LV interface). A typical film-coating spray could have between 15 and 60 m 2 of surface for each 100 ml of liquid sprayed! So, even at high bulk solution concentrations, are there going to be enough molecules to saturate the liquid surface to enable its surface tension to fall to bulk equilibrium values? Additionally, even if there are enough molecules in the bulk, will they have enough time to migrate to the surface of the droplet before the droplets collide with their target substrate? Twitchell et al. (1987) used the Gibbs absorption equation to calculate the number of molecules that would be needed to saturate the large surface area of a spray, and concluded that, with droplets up to about 140 µm mean diameter, there would be insufficient molecules, even with an aqueous HPMC E5 solution with a bulk concentration of 9 %w/w, to saturate the fresh liquid surface generated during atomization. The smaller the droplet, the larger the fresh surface area generated, thus the lower will be the degree of surface saturation and therefore the higher the surface tension. Twitchell et al. (1987) estimated that the surface tension of a 100 µm droplet of 9 %w/w HPMC E5 would be 61 mN/m; for a 50 µm droplet this would be 67 mN/m and a 25 µm diameter droplet would have a surface tension of 70 mN/m. They also calculated that above a mean droplet size of 143 µm there would be sufficient HPMC molecules to theoretically saturate the surface (as long as time was not a factor). It can be seen from the data in section 4.4 that the figures for droplet sizes quoted above are realistic for typical film-coating sprays. It will be appreciated that as the HPMC molecules migrate to the surface of the droplets, the concentration of HPMC remaining in the bulk of the droplet will be very low. This fact introduces another potential detrimental phenomenon, in that with dilute solutions there is a considerable time required for equilibrium surface tensions to be set up (as discussed above in the section on surface ageing). Page 125 The above observations lead to the conclusion that the surface tension of droplets hitting a tablet surface may be considerably greater than that predicted from measuring the bulk surface tension, this effect being more pronounced with smaller droplets and less concentrated solutions and possibly will be potentiated by the time taken for HPMC molecules to migrate to the freshly produced droplet surface. Wetting, penetration and spreading of film-coating solutions on tablet or multiparticulate surfaces may therefore not follow expected trends. Factors such as solvent evaporation during travel to the tablet, polymer polydispersity and the inclusion of formulation additives may also influence this phenomenon. 5.2.3 Contact angle Introduction When a droplet is in static (non-dynamic, equilibrium) contact with a flat surface, a number of things could happen. At the two extremes, the droplet could either sit as a discrete droplet with just a single point of contact (no wetting) or it could spread out completely to cover the whole surface (full wetting). In practice, film-coating droplets usually form a discrete entity somewhere in between these extremes (see Fig. 5.3 ). The angle of a tangent drawn from a point at the contact between solid-liquid-vapour at the edge of the drop is known as the contact angle. If the value of the contact angle (θ) is equal to 0° then the surface is completed wetted. As the degree of wetting decreases the contact angle increases. At 180° no wetting occurs. From this it can be concluded that any factors which influence the surface tension of the formulation and/or the interfacial tension will influence the degree of wetting. Surface-active agents, for instance, may decrease both γ LV and γ SL , the latter arising from their adsorption at the solid-liquid interface. The degree of spreading of a droplet is determined by Young’s equation: (5.1) where γ SV is the solid-vapour interfacial tension, γ SL is the solid-liquid interfacial tension and γ LV is the liquid-vapour interfacial tension. The principle of Young’s equation can be better understood by examining the sketches in Figs 5.4 and 5.5. At the periphery of the droplet there exists an equilibrium between the surface forces associated with the three surfaces at that point, i.e. the solid-vapour interface force in the plane of the solid surface in one direction is balanced by the sum of the resolved forces associated with the solid-liquid and liquid- vapour interfaces in the opposite direction. Therefore, at equilibrium γ SV =γ SL +γ LV .cos θ (5.2) Rearranging equation (5.2) gives γ LV .cos θ=γ SV −γ SL (5.3) Page 126 Fig. 5.3 Illustration of droplet contact angles θ ranging between 0 and 180°. then (5.4) Thus we have Young’s equation (equation (5.1)). Determination of the contact angle made by a liquid, solution or suspension of film-coating formulation on a surface has often been undertaken to assess the wettability of powders or tablet compositions and the wetting characteristics of Page 127 Fig. 5.4 Diagram of a droplet in equilibrium with a solid substrate, showing the balance of forces between γ SV , γ LV and γ SL . Fig. 5.5 Close-up of the edge of a liquid droplet on a solid surface and the explanation of Young’s equation. [...]... Davies, 19 85), as has the relationship between the contact angle and adhesion of coating formulations to different substrates (Wood & Harder, 1970; Harder et al., 1970; Nadkarni et al., 19 75) Alkan & Groves (1982) used contact angle measurement as an aid to calculating the penetration behaviour of an organic film -coating solution The tablet surface free energy and polarity and interactions with the coating. .. sessile drop on a horizontal surface and contact angle was first derived by Padday (1951) as (5 .5) In equation (5 .5), ρL and γLV are the density and equilibrium liquid surface tension of the coating solution and h is the measured height of the drop This equation was later amended by Kossen & Heertjes (19 65) to allow for the volume porosity of the compact (εv) They derived two equations For cos θ . more efficient and elegant films. Film coatings are invariably applied in the pharmaceutical industry by spraying a coating solution or suspension onto the. derived by Padday (1951) as (5 .5) In equation (5 .5), ρ L and γ LV are the density and equilibrium liquid surface tension of the coating solution and h is the