Tài liệu Pharmaceutical Coating Technology (Part 5) ppt

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 m

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

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

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 γLV Its typical SI units are mN/m

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

The corresponding symbol and unit for SL interfacial free energy are γSL 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 γSL and γSV 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 γSV 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

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

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

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 m2 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)

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 γLV and γSL, 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 γSV is the solid-vapour interfacial tension, γSL is the solid-liquid interfacial tension and γLV 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

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

Fig 5.4 Diagram of a droplet in equilibrium with a solid substrate, showing the balance of

forces between γSV, γLV and γSL

Fig 5.5 Close-up of the edge of a liquid droplet on a solid surface and the explanation of

Young’s equation

of test liquids (Harder et al., 1970; Zografi & Tam, 1976; Lerk et al., 1976; Fell & Efentakis, 1979; Buckton & Newton, 1986; Odidi et al., 1991) In addition, surface characteristics and surface energy values have been elucidated from contact angle measurements (Harder et al., 1970; Zografi & Tam,

1976; Liao & Zatz, 1979; Costa & Baszkin, 1985; Davies, 1985), 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., 1975) 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 solution components have been shown by Costa & Baszkin (1985) to influence the contact angle, spreading and penetration at the tablet surface They showed that the contact angles made by a series of polyols on tablets of various formulations were dependent on the tablet surface free energy, and that the constituents played a part in modifying this surface energy The authors also showed the tablet core constituents to influence tablet pore size and, consequently, penetration rates into the tablet

Thus, as far as aqueous film coating is concerned, measurement of contact angles may provide useful information on film adhesion, droplet spreading and penetration tendencies, and also interactions

between the constituents of the coating formulation and those of the tablet substrate

Measurement of contact angle

Various methods have been used to assess contact angles These include direct measurement using, for example, a telemicroscope or photographic technique; indirect measurement such as the h-e method, which involves measuring the maximum droplet height on a surface (Kossen & Heertjes, 1965; and see Fig 5.6) and by measurement of liquid penetration A review of the methods available has been made

by Stamm et al (1984) and a comparison of the h-e method and a direct measurement technique

reported by Fell & Efentakis (1979) Contact angle determination methods have been reviewed critically

by Buckton (1990)

The relationship between the maximum height of a 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 (1965) to allow for the volume porosity of the compact (εv) They derived two equations For cos θ<90°:

(5.6)

Fig 5.6 Determination of contact angle by the maximum droplet height technique of

Kossen & Heertjes (1965)

For cos θ>90°:

(5.7)

One further complication with contact angle determinations that is relevant to its measurement in the context of a coating droplet on a tablet surface is the effect of surface roughness This can be understood

by examining Fig 5.7 Close examination will show that the actual true contact angle (θt) at the point of

contact is the same in each case, but the measured (apparent) contact angles (θm) are very different

Contact angles in film coating

Most work performed on the wetting of pharmaceutical materials utilizing contact angle measurement has concentrated on measuring the angles of drops which have been placed carefully on a flat substrate surface In addition, the substrates have tended to be specially prepared, for example, either by using a high compaction pressure to minimize liquid penetration and reduce surface roughness or by using test solutions saturated with the components of the compacts in order to avoid any dissolution of the

substrate Although these techniques may give information of a

Fig 5.7 The effect of surface roughness on the apparent contact angle

fundamental nature, they do not reflect what may happen when film-coating solutions are applied in practice Little information is available at present regarding the influence of droplet momentum on the contact angle formed, the role of changes in film-coating formulations, or the contact angles formed on coated tablets

The contact angles formed by droplets on a substrate during aqueous film coating may potentially influence the roughness and appearance of the coated product The contact angle will also reflect the degree of liquid penetration into the substrate and, consequently, coat adhesion Young’s equation (equation (5.1)) equates the forces acting on a drop of liquid on a solid surface This equation implies that the contact angle is dependent upon the surface tension of the liquid, the solid-liquid interfacial tension and the surface tension of the solid Low contact angles are favoured by high solid and low liquid surface tensions and a low solid-liquid interfacial tension

Table 5.1 shows the data of Twitchell et al (1993) for some contact angle measurements of droplets

of HPMC E5 solutions approximately 1 s after being placed gently on uncoated and coated compacted tablet cores These results also indicate that the contact angles formed by HPMC-based formulations on coated tablets can be different from those formed on uncoated tablets Droplets placed gently on the surface of coated tablets showed greater initial contact angles than those on uncoated tablets, this being particularly apparent with the low-viscosity solutions Droplet viscosity appeared to have minimal influence on the contact angles formed by droplets placed gently on coated tablet surfaces These latter two findings are due to a reduction in droplet penetration into the coated tablet surface compared with the uncoated tablet surface The potential for very rough coated

surfaces to increase the observed contact angle of droplets placed gently on the surface is also

demonstrated in Table 5.1 This is likely to have arisen from a tendency for the rougher surface to resist movement across the surface, thereby reducing the advancement of the droplet

If we assume that (i) HPMC coating formulations of the type used in practice exhibit minimal

differences in their surface tension (section 4.2.3), (ii) the uncoated tablets are the same and (iii) the solid-liquid interfacial tensions are the same, it might be expected from theoretical considerations that the contact angles which the droplets make on the tablets during a coating process would be of the same order, irrespective of the coating conditions This indeed may be the case if (i) the substrate has zero porosity, (ii) the droplets have time to reach equilibrium on the substrate, (iii) the droplets are saturated with components of the substrate so that dissolution does not occur and (iv) no other external forces are acting on the spreading process In practical situations, however, the above conditions do not exist and there is therefore the potential for the droplet contact angles to be dependent upon the application conditions

The latter point (iv) is discussed further in section 5.4 in which the concept and usefulness of

determining dynamic contact angles is discussed in the context of droplet spreading on the substrate surface

5.2.4 Types of wetting

The process of wetting, as defined in section 5.2.1 above, can be subdivided into three distinct types:

adhesional, immersional and spreading wetting Each of these control the fate of the droplet of coating

solution after initial impact

Table 5.1 Contact angle of droplets of aqueous HPMC E5 solutions on uncoated and coated tablet cores

Fig 5.8 Schematic diagram of adhesional, immersional and spreading wetting

A pictorial theoretical representation of these types of wetting is shown in Fig 5.8 It depicts the gradual immersion of a cube from air into liquid It helps to illustrate the changes (either gains or losses)

in the surface areas of various interfaces that occur as this sequence proceeds It is the differences in the disappearance or appearance of the various interfaces that define the differences between the various types of wetting

In the transition from stage (a) to stage (b) in Fig 5.8, i.e to the point at which the cube just touches the surface of the liquid, there is a loss in area of both the solid-vapour and liquid-vapour interfaces and

a corresponding gain in a wetted solid-liquid interface This is adhesional wetting

As the cube becomes immersed in the liquid (stage (b) to stage (c) in Fig 5.8) there is loss of vapour (i.e ‘dry’) interface and a corresponding gain in solid-liquid (i.e wetted) interface Note,

solid-however, that there is no change in the area of the liquid-vapour interface, i.e there is neither loss nor gain of the liquid-vapour interface during this process of immersional wetting

Spreading wetting occurs between stages (c) to (d) in Fig 5.8, i.e as the liquid spreads over the top surface of the cube In this case there is again loss of solid-vapour and gain of solid-liquid interfaces but this time there is an increase in the area of liquid-vapour interface

The common thread in all types of wetting described above is that ‘dry’ solid-vapour interface is replaced by ‘wetted’ solid-liquid interface The differences in the fate of the liquid-vapour interface defines which type of wetting is occurring These differences are summarised below

• In all cases solid-vapour interface disappears

solid-liquid interface forms

• Adhesional wetting liquid-vapour interface disappears

So much for ‘textbook’ explanations, but what does this mean in the context of the film coating of tablets or multiparticulates? In the following set of diagrams, these concepts have been converted into visualizations of situations that arise during actual film coating

Adhesional wetting

Fig 5.9, which is a diagrammatic representation of adhesional wetting, shows a droplet of coating formulation approaching and hitting the surface of a tablet core or multiparticulate pellet The resulting collision will result in a loss of

Fig 5.9 Schematic representation of adhesional wetting in the context of film coating— 1:

Droplet collision

• Immersional wetting no change in liquid-vapour interface

• Spreading wetting liquid-vapour interface forms