Tài liệu Pharmaceutical Coating Technology (Part 5) ppt

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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.
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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.
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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.
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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
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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.
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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
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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).
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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)
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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
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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.
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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), ρ

L
and γ
LV
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 (
ε
v
). They derived two equations.
For cos
θ<90°:
(5.6)
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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 (θ
t
) at the point of
contact is the same in each case, but the measured (apparent) contact angles (
θ
m
) 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
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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