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Studies on direct compression of tablets XVI. The use of surface area measurements for the evaluation of bonding surface area in compressed powders
Powder
Technology,
47 11986) 201 - 209
201
Studies on Direct Compression of Tablets XVI. The use of surface area measurements for the evaluation of bonding surface area in compressed powders C. NYSTRGM
and P. G. KAREHILL
Department of Galenical Pharmacy, Uppsala (Sweden)
Uppsala Biomedical
(Received
form January
March 27,1985;
in revised
University of Uppsala, Box 580, S-751 23
17, 1986)
SUMMARY
Two non-porous materials, iron and sodium chloride, undergoing volume reduction mainly by plastic deformation, were compressed at pressures up to 300 MPa in an instrumented single-punch press. The compacts were characterized on radial tensile strength and surface area as measured by both a transient permeameter and a gas adsorption technique. For the iron powder, the compact strength increased almost linearly with the compression load after approximately 100 MPa, whereas the two surface characteristics remained unchanged over the whole pressure range, indicating that only a minute fraction of the external geometrical surface area was utilized for bonding. Although the surface area profiles for sodium chloride showed a more complex pattern, due to fragmentation and crack formation, it was believed that the bonding surface area for this material was also relatively low. By varying the amount of lubricant additions and by testing compacts after varying time after compression, it was further indicated that the surface area taking part in interparticulate attraction of sodium chloride is low. Although it cannot be excluded that bonding of the tested materials is due to long-range forces not affecting the surface areas measured, it seems that the two techniques tested are not capable of detecting the surface area utilized for bonding.
INTRODUCTION
During the compression of powders, several physico-chemical properties of the powdered material will influence the final strength of the coherent compact obtained. Some para0032-5910/86/$3.50
Center,
meters that have been studied, especially for pharmaceutical materials, are particle properties such as-size, shape and surface texture [ 1 - 51. Also volume reduction mechanisms, i. e, elastic deformation, plastic deformation and particle fragmentation have been studied in detail [6 - 91. Although such parameters could sometimes be directly related to compact strength, it is our opinion that they should be regarded as secondary parameters, indirectly affecting the bonding process within a compact [lo]. The primary parameters could subsequently be defined as a) the strength of the main bonding mechanisms involved, and b) the bonding surface area over which these bonds act. Unfortunately, relatively few attempts have been made to characterize these primary parameters directly. Some fundamental studies in the field of metallurgy [ll] have indicated that the surface area taking part in the attraction between compact particles is relatively small, being only a minor fraction of the geometrical surface area available. Studies on pharmaceutical materials, using gas adsorption techniques, have, however, suggested that larger surface areas are involved [ 12 - 151. In these studies, a decrease in surface area with compaction load has been regarded as a reflection of the surface area utilized for the bonding between particles. However, several difficulties regarding the interpretation of gas adsorption data for the evaluation of bonding surface areas have been pointed out [8, 13, 161. With increasing compaction load, more dense compacts will be formed, bringing particle surface areas into closer proximity. The surface area available for the gas molecules will then be dependent upon the penetration capacity of the 0
bevier
Sequoia/Printed
in The Netherlands
202
technique, i.e., mainly the size of the gas molecules used. For gases like nitrogen and krypton, that are normally used in these kind of studies, the molecules will only reach a fraction of the total tablet surface area. Since the distances between solid surfaces needed for the development of bonds could be substantially smaller than the size of the gas molecules, only a part of the ‘non-available’ surface area may be utilized for bonding [ 131. The gas adsorption technique will therefore, in principle, deliver an overestimation of bonding surface areas. If however, solid non-porous materials, undergoing volume reduction without any tendency towards fragmentation are used, some kind of proportional relation between the measured and the ‘true’ bonding surface area ought to be obtained, With few exceptions, the relations presented in the literature are more complex. Normally, an initial increase in tablet surface area with compaction load is recorded [12 - 141. This has been explained by a fragmentation of the compressed particles, resulting in the formation of new surfaces. Additionally, the use of porous materials and the possibility for pores and cracks to be closed during compression may further complicate the evaluation of a bonding surface area [8,16]. An attempt to overcome these problems for a porous, fragmenting material was presented by StanleyWood and Shubiar [15]. By using varying amounts of binder additions, the tablet surface area corresponding to zero compact strength was extrapolated. By a comparison with the powder surface area, the surface area created due to fragmentation was calculated and used as a material constant for the further evaluation of bonding surface areas. It is, however, doubtful that the fragmentation tendency is unaffected by additions of a second component. It has been shown that minor additions of, for example, binder materials [lo], lubricants and water [17] can strongly decrease particle fragmentation during compression. Furthermore, the addition of a binder as a solution could probably lead to a closure of open pores and cracks, thereby reducing further the measured tablet surface area and the possibility of estimating the surface area used for bonding. The approach described [ 151 should be useful if applied to materials known to deform mainly
by plastic deformation during compression. In order to obtain compacts with varying strength, another method could be to add small quantities of magnesium stearate, which has been shown to decrease compact strength for a number of plastically deforming materials [8, 91. The additions could then be kept extremely low and the admixture could be obtained by a dry mixing process. In studies using permeametry to characterize the surface area of compacts [16, 181, the results indicate that the final compact can often be regarded as a large agglomerate, which is being kept together by a number of bonding points of relatively small surface area, It was believed that the possibility of measuring the surface area of compacts with equations similar to those used for the characterization of powder plugs, supports such a model. It has been shown that for sodium chloride and saccharose, two non-porous materials, the permeameter technique gave results in acceptable agreement with gas adsorption data. For very dense compacts, the permeametry technique gave overestimated surface areas [ 161. It therefore seems that the permeametry technique has a lower capacity to reach and detect the ‘total’ surface area within a compact. However, provided that high compression loads are avoided, the technique ought to be potentially useful for the evaluation of bonding surface areas. A specific advantage is that the presence of open pores and cracks would not complicate the evaluation. The objective of the present study was to test the usefulness of surface area measurements by permeametry and gas adsorption for the evaluation of bonding surface areas in compressed powders. For these measurements, both a metallic and a pharmaceutical powder, deforming mainly by plastic deformation during compaction, were chosen as model substances.
EXPERIMENTAL
Material
Two materials regarded as non-porous and undergoing volume reduction mainly by plastic deformation were chosen as test materials. Sodium chloride (cubic crystalline, puriss,
203
Kebo-Grave, Sweden) was fractionated by dry sieving to obtain the fraction 250 - 355 pm. Iron (powder, puriss, Kebo-Grave, Sweden) was used as supplied. The iron powder was relatively fine particulate and the specific surface area was 531 cm2/g as measured by permeametry. To study the effect of lubricant addition on compact properties, a compound known to reduce bonding was tested [9] . Magnesium stearate (Ph. Nord.) was used as supplied. Primary characteristics of the test materials are presented in Fig. 1 and the Table.
its extreme upper position. Immediately after ejection, the motor was stopped and the compact collected. This procedure gave an almost constant load rate, corresponding to a machine speed of 30 rpm and a consolition time of 150 ms for sodium chloride and the iron powder respectively. The maximum compression loads were within +3% of the mean values presented. For the compaction of pure materials, without lubricant admixture, the punch faces and the die wall were lubricated before each compaction with a lwt.% magnesium stearate suspension in ethanol. Before any compact characterization, the specimens were stored for at least 2 days, if not stated otherwise, under the abovementioned conditions.
TABLE Primary characteristics of powders Material
DensiL;a (gem )
Gas adsorption surface area (cm2 g-l)
Iron Sodium chloride Magnesium stearate
7.66 2.17 1.06
860 100 23000
aMeasured with an Air Comparison Pycnometer Model 930 (Beckman, U.S.A.).
Methods Powder compression
All powders and powder mixtures were stored for not less than 2 days at 20 “C and 45% relative humidity. Compacts were then made in an instrumented single-punch press (Korsch EK 0, Federal Republic of Germany) at 30 rpm using flat-faced punches with a diameter of 1.13 cm. During all experiments, the distance between the punches at zero compression load was held constant at 0.300 cm. The different compression loads (maximum upper punch pressures) were obtained by varying the amount of powder filled into the die. This procedure delivered compacts of sodium chloride with masses between 0.57 and 0.76 g. The corresponding values for the iron powder were 1.28 and 1.82 g. After manual filling of the die, each compact was prepared by starting the motor of the press when the upper punch was in
Measurement
of compact
strength
The compacts were measured for crushing strength in a Heberlein diametral compression test apparatus (TBH-28, ERWEKA, Federal Republic of Germany). Since all compacts showed approximately normal tensile failure, the radial tensile strength was calculated [ 191. Results presented are mean values of at least ten determinations. The precision, expressed as the coefficient of variation, was normally better than 10%.
Measurement
of gas adsorption
surface
area
The specific surface areas of both powders and compacts were measured by low-temperature krypton adsorption in an Alfa-Met 6E (Studsvik, AB Atomenergi, Sweden), with liquid nitrogen as coolant [20]. Prior to adsorption measurements, the samples were degassed for at least 24 h at ambient temperature (23 f 1 “C) and a vacuum of less than 10V4 Torr. The amount of powder or the number of tablets used for each measurement were chosen to give a total surface area exceeding 500 cm2. The specific surface areas were calculated with the B.E,T. equation in the relative pressure range of 0.05 - 0.35.
Measurement
of permeametry
surface
area
A weighed amount of powder was filled in a specially constructed die, sealed at one end by a plate [ 161. The die and plate was placed on the table of the instrumented press
204
(4
(b)
(4
Fig. 1. Photomicrographs of materials: above, iron (a) before and (b) after compression; below, sodium chloride (c) before and (d) after compression (150 MPa). The specimens photographed in a scanning electron microscope (SMU-3, JEOL, Japan).
205
and the powder was compressed by hand, using the punch described above. After compaction, the die, containing the compact, was connected to a Blaine permeameter as described elsewhere [ 161. The permeability of the compacts were then measured after at least 1 h after compression, if not stated otherwise. The compact surface area was calculated as described earlier [ 161, using terms for both viscous and molecular flow. Procedures for evaluating bonding surface area (i) Variation of compression load In this experiment, compact strength and surface area were monitored for both materials. The intention was to find out whether an increase in strength was reflected by a decrease in compact surface area. (ii) Variation of lubricant admixture Small amounts of magnesium stearate were admixed with sodium chloride (50 g) in a Turbula mixer (W. A. Bachofen, Switzerland) for 3000 min. The long mixing time and the minute amounts of lubricant used were chosen in order to obtain a film around the sodium chloride particles [21] that would decrease the bonding ability without changing the surface area of the uncompressed powder. The intention was to find out if a subsequent decrease in strength was
reflected by an increase in compact surface area. If such a relationship was established, it would be interesting to apply the procedure reported by Stanley-Wood and Shubair [ 151, to calculate bonding surface area. (iii) Variation of time between compression and compact characterization The intention was to relate the described increase in compact strength with time for sodium chloride [22] to any measurable change in permeametry surface area. Due to the short time before an equilibrium strength is obtained, it was not possible to characterize the compacts on gas adsorption surface.
RESULTS AND DISCUSSION
Effect of compression load on compact surface area The characteristics of both iron and sodium chloride compacts, compressed at increasing loads, are presented in Fig. 2. The compact strength increased approximately linearly for both materials tested. The minimum load at which coherent compacts could be obtained was about 100 and 50 MPa for iron and sodium chloride respectively. The slope of the linear part of the strength-pressure profile was approximately three times higher for iron than for sodium chloride, indicating that the
Fig. 2. The effect of compression load on compact strength (0) and compact surface area as measured by gas adsorption (A) and permeametry (o), for iron (closed symbols) and sodium chloride (open symbols).
206
iron powder was bonding with a stronger bond type or that the surface area utilized for bonding was higher. Assuming that the major bond types involved are unchanged with increasing pressure, it seems reasonable that an increase in strength is accompanied by a proportional increase in bonding surface area. If the permeametry and gas adsorption techniques are capable of detecting such an increase in bonding surface area, results would be expected showing a decrease in compact surface area after 100 and 50 MPa for the two materials respectively. However, for the iron compacts, the surface areas obtained by both permeametry and gas adsorption (Fig. 2) seem to be fairly constant with increasing pressure. For permeametry, even a slight increase was observed. It could, however, be questioned whether this is an artefact or not. In an earlier study [16], it was shown that measurements on powders compressed at relatively high loads could result in an overestimation of compact surface area. The surface areas measured by gas adsorption showed an appreciable variation, especially at high loads, making it difficult to draw firm conclusions. The result could not be interpreted as giving a significant decrease in compact surface area with compression load, after 100 MPa. The relatively small difference in surface area obtained by the two techniques investigated supports the idea that the iron particles were essentially non-porous. The small difference obtained could be due to the irregular surface texture of the iron particles (Fig. l), which would not be detected by the permeametric technique. The lack of increase in permeametry surface area with increased compression load indicates that the iron particles were not significantly fragmenting during compression. The data obtained for the iron powder therefore indicate that the surface area utilized for interparticulate attraction is equal to or less than the precision of the surface area methods tested. Since it is reasonable to assume that these methods will tend to overestimate the bonding surface area [ 131, as discussed in the Introduction, the results imply that the bonding surface area in the iron compacts is very small [ll]. The surface area profiles for sodium chloride (Fig. 2) show a different pattern. Initially,
the permeametry surface area shows a moderate increase, whereafter an extensive increase is observed. Although the data obtained at higher pressures presumably correspond to an overestimation of the surface area [16], the results indicate that volume reduction of sodium chloride is accompanied by some tendency towards particle fragmentation. The term fragmentation here means that a number of new, smaller, discrete particles are created from the original particles [8] . The surface area as measured by gas adsorption shows initially a higher increase with compression load than the corresponding data obtained by permeametry. This probably reflects the fact that cracks and pores were formed during compression. After approximately 75 to 100 MPa, the surface area decreases with an increase in compression load. Several interpretations are possible for the surface area profiles obtained for sodium chloride. The initial increase in surface area as observed by both methods indicates both particle fragmentation and formation of cracks and pores. This is supported by S.E.M. photographs (Fig. 1). The subsequent decrease in gas adsorption surface area could then be a reflection of an increase in bonding surface area. This means that sodium chloride particles bond with a significantly weaker bond type than the iron particles, resulting in weaker compacts but utilizing a larger surface area for interparticulate attraction, which subsequently is reflected in the decrease of gas adsorption surface area. This decrease could alternatively be interpreted as a sealing of the cracks created. Considering the profiles obtained for the iron powder, the latter explanation seems more probable. The results therefore indicate that the bonding surface area for sodium chloride is relatively small. Effect of lubricant addition on compact surface area The data for sodium chloride compacts obtained at varying loads (Fig. 2) indicated that several processes which could influence the measured surface areas were affected simultanously. In an attempt to vary the degree of bonding without changing the compression load and subsequently not affecting the fragmentation tendency or
207
formation of cracks, mixtures of sodium chloride and varying amounts of magnesium stearate were compressed at 150 MPa. The effect of increasing additions of the lubricant on both compact strength and surface area for sodium chloride is presented in Fig. 3.
d
oo.-
0.050
3 1000
1
E
h
G
I
2
v
OJ 0
I,
O.OOL
Rq =
,/
0.050
0.00.9
500,
OJ 0
IX
O.OOL
CONCENTRATION
0.008
OF MAGNESIUM
STEARATE
I,
been obtained for silica compacts [23], where only a small amount of adsorbed water decreases the compact strength considerably, whereafter the strength remained fairly constant when the adsorption of water was further increased. One possible interpretation of the data obtained could be that two different bond types are involved in the interparticulate attraction. One bonding mechanism (e.g., molecular forces of Van der Waals type) could then be very sensitive for surface changes, while the other mechanism (e.g., solid bridges due to ionic bonding) could be established even in the presence of a lubricant film by, for example, a penetration by point irregularities. When a total surface coverage of sodium chloride particles by magnesium stearate is obtained, the latter bond type alone would determine the compact strength. In order to calculate the fraction R, of the external surface area that is covered by magnesium stearate ‘particles’, the following approximate equation could be used [ 241:
0.050 ,W,war
Fig. 3. The effect of lubricant concentration on compact strength and surface area for sodium chloride, compressed at 150 MPa.
Using minute additions, the compact strength decreased strongly with increasing magnesium stearate concentrations. This is in agreement with results reported earlier [8, 9, 213, where this effect was explained in terms of the formation of a lubricant film around the compound particles. However, at additions in excess of approximately 0.005 wt.%, the compact strength levelled off and even the use of a relatively high concentration (0.05 wt.%) gave no further reduction in strength. Similar profiles have
f3 &
1
(1 -f3)%m ; Assuming that the ratio of the surface and projected area shape coefficient (s/k) is equal to 4 [25], the surface area fraction for an addition of 0.005 wt.% magnesium stearate having a specific surface area of 2.3 m2/g (see the Table) is only 0.00288. To obtain a total surface coverage, corresponding to an R, of unity, a specific surface area of not less than 800 m2/g would be needed. This corresponds to a’particle’ size of magnesium stearate of the order of 50 - 100 a [26]. The small amount needed to reach the plateau therefore probably corresponds to the formation of a monomolecular film around the sodium chloride particles [ 211. As evident from Fig. 3, the admixture of the different lubricant amounts did not affect the powder surface area as characterized by the gas adsorption technique. However, the gas adsorption surface area of the corresponding compacts showed a decrease with increased quantities of lubricant. This effect was not expected, considering the obtained decrease in compact strength, which was supposed to expose the surface area used for
208
bonding. It was therefore not meaningful to apply the extrapolation procedure described by Stanley-Wood and Shubair [ 151. The result could probably be explained by a reduction in particle fragmentation and crack formation in the systems containing lubricant additions. Similar observations have been reported earlier [ 171. The results therefore indicate that the surface area used for bonding is relatively small, and masked by the surface area changes due to fragmentation and crack formation. The compact surface area as measured by permeametry shows an increase with lubricant addition, This result is probably due to an increased error at increasing lubricant concentrations. The equation used for the calculation of permeametry surface area does not seem to be valid for dense, low-porous compacts, as discussed for the results in Fig. 2. It was observed that the addition of magnesium stearate slightly decreased the compact porosity, which then would produce a further overestimation of the measured surface area.
Effect of ageing time on compact surface area The results in Figs. 2 and 3 have clearly demonstrated that it is difficult to obtain absolute measures of compact surface area for dense compacts by permeametry. However, the permeability measurements of sodium chloride compacts seemed to be very sensitive to small changes in compact porosity, as demonstrated for compacts containing varying amounts of lubricant (Fig. 3). Unfortunately, these changes in porosity were probably not due to changes in bonding surface area, but reflected a change in the packing ability of the sodium chloride particles. In order to utilize the sensitivity of the permeametry for the detection of bonding surface area, the technique was applied for the monitoring of surface area with ageing time of compacts. Results for both compact strength and permeametry surface area are presented in Fig. 4. Ageing time here means the waiting time between compaction and compact characterization, The compact strength was almost doubled within a few minutes. Such effects have been frequently reported for sodium chlor-
i a
:i____+i, 0
i 10
20 TIME
30
1500
lmtni
5 0.
Fig. 4. The effect of ageing time on compact strength (0) and compact surface area as measured by permeametry (0) for sodium chloride, compressed at 150 MPa. Error bars represents the 95% confidence interval for the mean.
ide [22]. The compact surface area as measured by permeametry, on the other hand, remained practically constant with ageing time [16]. It seems therefore that the increase in the bonding surface area, as reflected by the increase in compact strength, is either small or could not be detected by permeametry. In relation to the results discussed earlier (Figs. 2, 3), the most probable explanation seems to be that the bonding surface area is too small to be detected. However, it could not be excluded that the increase in compact strength with time (Fig. 4) could be due to two bonding mechanisms. The initial strength would then be due to one bond type, followed by a time-dependent increase in strength due to a continous formation of bonds of the second type. This second bonding mechanism must then be active over relatively long distances (e.g., Van der Waals forces) in order to explain why the compact permeability will not be decreased when these bonds are established. The time-dependency could be due to plastic flow caused by stress relaxation, bringing surfaces into closer proximity.
CONCLUSIONS
The results obtained demonstrate the problems involved when investigating the compaction behaviour of pharmaceutical materials. Although sodium chloride in pharmaceutical studies [8, 9, 141 normally represents a nearly ideal model substance (non-porous and consolidating by plastic deformation), it is evident from the present study that sodium chloride must be classified
209
as a complex substance with respect to its compaction behaviour. In contrast to the iron powder, sodium chloride particles undergo such changes during compression (fragmentation and formation of cracks and pores) that a simple monitoring of changes in surface area with pressure (Fig. 2) cannot unambigously be used for the evaluation of bonding surface area. Considering the even more complex nature of most pharmaceutical materials used in some reported studies [8, 12 - 151 it is questionable whether the interpretations suggested, purporting relatively high bonding surface areas [ 12 - 151, are justified solely on the basis of previously published experimental data. The results in the present study indicate that the surface area taking part in the interparticulate attraction for sodium chloride, as well as for iron powder, is small in relation to the geometrical surface area available. It cannot be excluded that bonding is facilitated by long-range forces (e.g., molecular forces of the Van der Waals type), thereby explaining why the two surface area techniques are not capable of detecting any substantial change in bonding surface area with changes in the different parameters tested.
ACKNOWLEDGEMENTS
The authors are very grateful to Mr. B. Johansson for skilful technical assistance and to Mrs. Eva Nises Ahlgren for preparing the manuscript. One of us (C.N.) is grateful to the Swedish Academy of Pharmaceutical Sciences for financial support.
LIST OF SYMBOLS
weight fraction of fine material (lubricant) in the binary mixtures k projected area shape coefficient surface fraction of coarse material 8 (sodium chloride) covered by the fine material SWC weight specific surface area of coarse material, mz g-l
f3
swf oc,
weight specific surface material, m2 g-r surface shape coefficient
area of fine
REFERENCES 1 J. A. Hersey, G. Bayraktar and E. Shotton, J. Pharm. Pharmacol. Suppl., 19 (1967) 24s. J. Pharm. Pharma2 E. Shotton and D. Ganderton, col. Suppl, 13 (1961) 144 T. 3 G. AIderborn and C. Nystriim, Acta Pharm. Suet., 19 (1982) 381. 4 J. Lazarus and L. Lachman, J. Pharm. Sci., 55 (1966) 1121. 5 G. Alderborn and C. Nystrom, Acta Pharm. Suet., 19 (1982) 147. 6 R. W. Heckel, Trans. Metall. Sot. AIME, 221 (1961) 671. I R. W. Heckel, Trans. Metall. Sot. AIME, 221 (1961) 1001. 8 M. Duberg and C. Nystriim, Acta Pharm. Suet., 19 (1982) 421. 9 A. H. de Boer, G. K. Bolhuis and C. F. Lerk, Powder Technol., 25 (1978) 75. 10 M. Duberg and C. Nystrom, Znt. J. Pharm. Technol. Prod. Mfr., in press. 11 F. P. Bowden and D. Tabor, The Friction and Lubrication of Solids, Oxford University Press, New York, 1950. 12 T. Higuchi, A N. Rao, L. W. Busse and J. V. Switosky, J. Am. Pharm. Assoc., Sci. Ed., 42 (1953) 194. 13 J. S. Hardman and B. A. LiIIey, Proc. R. Sot. Lond., A333 (1973) 183. Powder 14 N. A. Armstrong and R. F. Haines-Nutt, Technol., 9 (1974) 287. 15 N. G. Stanley-Wood and M. S. Shubair, Powder Technol., 25 (1980) 57. 16 G. AIderborn, M. Duberg and C. Nystrom, Powder Technol., 41 (1985) 49. and R. F. Haines-Nutt, Proc. 17 N. A Armstrong 1st. Znt. Conf Compaction Consol. Part. Matter, 19 72, Brighton, Powder Advisory Centre, London, 1974, p. 161. 18 G. AIderborn and C. Nystrom, Powder Technol., 44 (1985) 37. 19 J. T. Fell and J. M. Newton, J. Pharm. Sci., 59 (1970) 688. 20 J. Chyssler and B. Gronroos, Workreport BP78/l 7, AB Atomenergi, Studsvik, S-611 01 Nykoping, Sweden. 21 G. K. Bolhuis, C. F. Lerk, H. T. Zijlstra and A H. de Boer, Pharm. Weekblad, 110 (1975)317. 22 J. E. Rees and E. Shotton, J. Pharm. Pharmacol. suppz., 22 (1970) 17. 23 D. Dollimore and G. R. Heal, J. Appl. Chem., 11 (1961) 459. 24 C. Nystriim, J. Mazur and J. Sjiigren, Znt. J. Pharm., 10 (1982) 209. 25 T. Allen, Particle Size Measurement, Chapman and Hall, London, 2nd edn., 1974, p. 202. 26 T. Allen, Particle Size Measurement, Chapman and Hall, London, 2nd edn., 1974, p. 80.
Technology,
47 11986) 201 - 209
201
Studies on Direct Compression of Tablets XVI. The use of surface area measurements for the evaluation of bonding surface area in compressed powders C. NYSTRGM
and P. G. KAREHILL
Department of Galenical Pharmacy, Uppsala (Sweden)
Uppsala Biomedical
(Received
form January
March 27,1985;
in revised
University of Uppsala, Box 580, S-751 23
17, 1986)
SUMMARY
Two non-porous materials, iron and sodium chloride, undergoing volume reduction mainly by plastic deformation, were compressed at pressures up to 300 MPa in an instrumented single-punch press. The compacts were characterized on radial tensile strength and surface area as measured by both a transient permeameter and a gas adsorption technique. For the iron powder, the compact strength increased almost linearly with the compression load after approximately 100 MPa, whereas the two surface characteristics remained unchanged over the whole pressure range, indicating that only a minute fraction of the external geometrical surface area was utilized for bonding. Although the surface area profiles for sodium chloride showed a more complex pattern, due to fragmentation and crack formation, it was believed that the bonding surface area for this material was also relatively low. By varying the amount of lubricant additions and by testing compacts after varying time after compression, it was further indicated that the surface area taking part in interparticulate attraction of sodium chloride is low. Although it cannot be excluded that bonding of the tested materials is due to long-range forces not affecting the surface areas measured, it seems that the two techniques tested are not capable of detecting the surface area utilized for bonding.
INTRODUCTION
During the compression of powders, several physico-chemical properties of the powdered material will influence the final strength of the coherent compact obtained. Some para0032-5910/86/$3.50
Center,
meters that have been studied, especially for pharmaceutical materials, are particle properties such as-size, shape and surface texture [ 1 - 51. Also volume reduction mechanisms, i. e, elastic deformation, plastic deformation and particle fragmentation have been studied in detail [6 - 91. Although such parameters could sometimes be directly related to compact strength, it is our opinion that they should be regarded as secondary parameters, indirectly affecting the bonding process within a compact [lo]. The primary parameters could subsequently be defined as a) the strength of the main bonding mechanisms involved, and b) the bonding surface area over which these bonds act. Unfortunately, relatively few attempts have been made to characterize these primary parameters directly. Some fundamental studies in the field of metallurgy [ll] have indicated that the surface area taking part in the attraction between compact particles is relatively small, being only a minor fraction of the geometrical surface area available. Studies on pharmaceutical materials, using gas adsorption techniques, have, however, suggested that larger surface areas are involved [ 12 - 151. In these studies, a decrease in surface area with compaction load has been regarded as a reflection of the surface area utilized for the bonding between particles. However, several difficulties regarding the interpretation of gas adsorption data for the evaluation of bonding surface areas have been pointed out [8, 13, 161. With increasing compaction load, more dense compacts will be formed, bringing particle surface areas into closer proximity. The surface area available for the gas molecules will then be dependent upon the penetration capacity of the 0
bevier
Sequoia/Printed
in The Netherlands
202
technique, i.e., mainly the size of the gas molecules used. For gases like nitrogen and krypton, that are normally used in these kind of studies, the molecules will only reach a fraction of the total tablet surface area. Since the distances between solid surfaces needed for the development of bonds could be substantially smaller than the size of the gas molecules, only a part of the ‘non-available’ surface area may be utilized for bonding [ 131. The gas adsorption technique will therefore, in principle, deliver an overestimation of bonding surface areas. If however, solid non-porous materials, undergoing volume reduction without any tendency towards fragmentation are used, some kind of proportional relation between the measured and the ‘true’ bonding surface area ought to be obtained, With few exceptions, the relations presented in the literature are more complex. Normally, an initial increase in tablet surface area with compaction load is recorded [12 - 141. This has been explained by a fragmentation of the compressed particles, resulting in the formation of new surfaces. Additionally, the use of porous materials and the possibility for pores and cracks to be closed during compression may further complicate the evaluation of a bonding surface area [8,16]. An attempt to overcome these problems for a porous, fragmenting material was presented by StanleyWood and Shubiar [15]. By using varying amounts of binder additions, the tablet surface area corresponding to zero compact strength was extrapolated. By a comparison with the powder surface area, the surface area created due to fragmentation was calculated and used as a material constant for the further evaluation of bonding surface areas. It is, however, doubtful that the fragmentation tendency is unaffected by additions of a second component. It has been shown that minor additions of, for example, binder materials [lo], lubricants and water [17] can strongly decrease particle fragmentation during compression. Furthermore, the addition of a binder as a solution could probably lead to a closure of open pores and cracks, thereby reducing further the measured tablet surface area and the possibility of estimating the surface area used for bonding. The approach described [ 151 should be useful if applied to materials known to deform mainly
by plastic deformation during compression. In order to obtain compacts with varying strength, another method could be to add small quantities of magnesium stearate, which has been shown to decrease compact strength for a number of plastically deforming materials [8, 91. The additions could then be kept extremely low and the admixture could be obtained by a dry mixing process. In studies using permeametry to characterize the surface area of compacts [16, 181, the results indicate that the final compact can often be regarded as a large agglomerate, which is being kept together by a number of bonding points of relatively small surface area, It was believed that the possibility of measuring the surface area of compacts with equations similar to those used for the characterization of powder plugs, supports such a model. It has been shown that for sodium chloride and saccharose, two non-porous materials, the permeameter technique gave results in acceptable agreement with gas adsorption data. For very dense compacts, the permeametry technique gave overestimated surface areas [ 161. It therefore seems that the permeametry technique has a lower capacity to reach and detect the ‘total’ surface area within a compact. However, provided that high compression loads are avoided, the technique ought to be potentially useful for the evaluation of bonding surface areas. A specific advantage is that the presence of open pores and cracks would not complicate the evaluation. The objective of the present study was to test the usefulness of surface area measurements by permeametry and gas adsorption for the evaluation of bonding surface areas in compressed powders. For these measurements, both a metallic and a pharmaceutical powder, deforming mainly by plastic deformation during compaction, were chosen as model substances.
EXPERIMENTAL
Material
Two materials regarded as non-porous and undergoing volume reduction mainly by plastic deformation were chosen as test materials. Sodium chloride (cubic crystalline, puriss,
203
Kebo-Grave, Sweden) was fractionated by dry sieving to obtain the fraction 250 - 355 pm. Iron (powder, puriss, Kebo-Grave, Sweden) was used as supplied. The iron powder was relatively fine particulate and the specific surface area was 531 cm2/g as measured by permeametry. To study the effect of lubricant addition on compact properties, a compound known to reduce bonding was tested [9] . Magnesium stearate (Ph. Nord.) was used as supplied. Primary characteristics of the test materials are presented in Fig. 1 and the Table.
its extreme upper position. Immediately after ejection, the motor was stopped and the compact collected. This procedure gave an almost constant load rate, corresponding to a machine speed of 30 rpm and a consolition time of 150 ms for sodium chloride and the iron powder respectively. The maximum compression loads were within +3% of the mean values presented. For the compaction of pure materials, without lubricant admixture, the punch faces and the die wall were lubricated before each compaction with a lwt.% magnesium stearate suspension in ethanol. Before any compact characterization, the specimens were stored for at least 2 days, if not stated otherwise, under the abovementioned conditions.
TABLE Primary characteristics of powders Material
DensiL;a (gem )
Gas adsorption surface area (cm2 g-l)
Iron Sodium chloride Magnesium stearate
7.66 2.17 1.06
860 100 23000
aMeasured with an Air Comparison Pycnometer Model 930 (Beckman, U.S.A.).
Methods Powder compression
All powders and powder mixtures were stored for not less than 2 days at 20 “C and 45% relative humidity. Compacts were then made in an instrumented single-punch press (Korsch EK 0, Federal Republic of Germany) at 30 rpm using flat-faced punches with a diameter of 1.13 cm. During all experiments, the distance between the punches at zero compression load was held constant at 0.300 cm. The different compression loads (maximum upper punch pressures) were obtained by varying the amount of powder filled into the die. This procedure delivered compacts of sodium chloride with masses between 0.57 and 0.76 g. The corresponding values for the iron powder were 1.28 and 1.82 g. After manual filling of the die, each compact was prepared by starting the motor of the press when the upper punch was in
Measurement
of compact
strength
The compacts were measured for crushing strength in a Heberlein diametral compression test apparatus (TBH-28, ERWEKA, Federal Republic of Germany). Since all compacts showed approximately normal tensile failure, the radial tensile strength was calculated [ 191. Results presented are mean values of at least ten determinations. The precision, expressed as the coefficient of variation, was normally better than 10%.
Measurement
of gas adsorption
surface
area
The specific surface areas of both powders and compacts were measured by low-temperature krypton adsorption in an Alfa-Met 6E (Studsvik, AB Atomenergi, Sweden), with liquid nitrogen as coolant [20]. Prior to adsorption measurements, the samples were degassed for at least 24 h at ambient temperature (23 f 1 “C) and a vacuum of less than 10V4 Torr. The amount of powder or the number of tablets used for each measurement were chosen to give a total surface area exceeding 500 cm2. The specific surface areas were calculated with the B.E,T. equation in the relative pressure range of 0.05 - 0.35.
Measurement
of permeametry
surface
area
A weighed amount of powder was filled in a specially constructed die, sealed at one end by a plate [ 161. The die and plate was placed on the table of the instrumented press
204
(4
(b)
(4
Fig. 1. Photomicrographs of materials: above, iron (a) before and (b) after compression; below, sodium chloride (c) before and (d) after compression (150 MPa). The specimens photographed in a scanning electron microscope (SMU-3, JEOL, Japan).
205
and the powder was compressed by hand, using the punch described above. After compaction, the die, containing the compact, was connected to a Blaine permeameter as described elsewhere [ 161. The permeability of the compacts were then measured after at least 1 h after compression, if not stated otherwise. The compact surface area was calculated as described earlier [ 161, using terms for both viscous and molecular flow. Procedures for evaluating bonding surface area (i) Variation of compression load In this experiment, compact strength and surface area were monitored for both materials. The intention was to find out whether an increase in strength was reflected by a decrease in compact surface area. (ii) Variation of lubricant admixture Small amounts of magnesium stearate were admixed with sodium chloride (50 g) in a Turbula mixer (W. A. Bachofen, Switzerland) for 3000 min. The long mixing time and the minute amounts of lubricant used were chosen in order to obtain a film around the sodium chloride particles [21] that would decrease the bonding ability without changing the surface area of the uncompressed powder. The intention was to find out if a subsequent decrease in strength was
reflected by an increase in compact surface area. If such a relationship was established, it would be interesting to apply the procedure reported by Stanley-Wood and Shubair [ 151, to calculate bonding surface area. (iii) Variation of time between compression and compact characterization The intention was to relate the described increase in compact strength with time for sodium chloride [22] to any measurable change in permeametry surface area. Due to the short time before an equilibrium strength is obtained, it was not possible to characterize the compacts on gas adsorption surface.
RESULTS AND DISCUSSION
Effect of compression load on compact surface area The characteristics of both iron and sodium chloride compacts, compressed at increasing loads, are presented in Fig. 2. The compact strength increased approximately linearly for both materials tested. The minimum load at which coherent compacts could be obtained was about 100 and 50 MPa for iron and sodium chloride respectively. The slope of the linear part of the strength-pressure profile was approximately three times higher for iron than for sodium chloride, indicating that the
Fig. 2. The effect of compression load on compact strength (0) and compact surface area as measured by gas adsorption (A) and permeametry (o), for iron (closed symbols) and sodium chloride (open symbols).
206
iron powder was bonding with a stronger bond type or that the surface area utilized for bonding was higher. Assuming that the major bond types involved are unchanged with increasing pressure, it seems reasonable that an increase in strength is accompanied by a proportional increase in bonding surface area. If the permeametry and gas adsorption techniques are capable of detecting such an increase in bonding surface area, results would be expected showing a decrease in compact surface area after 100 and 50 MPa for the two materials respectively. However, for the iron compacts, the surface areas obtained by both permeametry and gas adsorption (Fig. 2) seem to be fairly constant with increasing pressure. For permeametry, even a slight increase was observed. It could, however, be questioned whether this is an artefact or not. In an earlier study [16], it was shown that measurements on powders compressed at relatively high loads could result in an overestimation of compact surface area. The surface areas measured by gas adsorption showed an appreciable variation, especially at high loads, making it difficult to draw firm conclusions. The result could not be interpreted as giving a significant decrease in compact surface area with compression load, after 100 MPa. The relatively small difference in surface area obtained by the two techniques investigated supports the idea that the iron particles were essentially non-porous. The small difference obtained could be due to the irregular surface texture of the iron particles (Fig. l), which would not be detected by the permeametric technique. The lack of increase in permeametry surface area with increased compression load indicates that the iron particles were not significantly fragmenting during compression. The data obtained for the iron powder therefore indicate that the surface area utilized for interparticulate attraction is equal to or less than the precision of the surface area methods tested. Since it is reasonable to assume that these methods will tend to overestimate the bonding surface area [ 131, as discussed in the Introduction, the results imply that the bonding surface area in the iron compacts is very small [ll]. The surface area profiles for sodium chloride (Fig. 2) show a different pattern. Initially,
the permeametry surface area shows a moderate increase, whereafter an extensive increase is observed. Although the data obtained at higher pressures presumably correspond to an overestimation of the surface area [16], the results indicate that volume reduction of sodium chloride is accompanied by some tendency towards particle fragmentation. The term fragmentation here means that a number of new, smaller, discrete particles are created from the original particles [8] . The surface area as measured by gas adsorption shows initially a higher increase with compression load than the corresponding data obtained by permeametry. This probably reflects the fact that cracks and pores were formed during compression. After approximately 75 to 100 MPa, the surface area decreases with an increase in compression load. Several interpretations are possible for the surface area profiles obtained for sodium chloride. The initial increase in surface area as observed by both methods indicates both particle fragmentation and formation of cracks and pores. This is supported by S.E.M. photographs (Fig. 1). The subsequent decrease in gas adsorption surface area could then be a reflection of an increase in bonding surface area. This means that sodium chloride particles bond with a significantly weaker bond type than the iron particles, resulting in weaker compacts but utilizing a larger surface area for interparticulate attraction, which subsequently is reflected in the decrease of gas adsorption surface area. This decrease could alternatively be interpreted as a sealing of the cracks created. Considering the profiles obtained for the iron powder, the latter explanation seems more probable. The results therefore indicate that the bonding surface area for sodium chloride is relatively small. Effect of lubricant addition on compact surface area The data for sodium chloride compacts obtained at varying loads (Fig. 2) indicated that several processes which could influence the measured surface areas were affected simultanously. In an attempt to vary the degree of bonding without changing the compression load and subsequently not affecting the fragmentation tendency or
207
formation of cracks, mixtures of sodium chloride and varying amounts of magnesium stearate were compressed at 150 MPa. The effect of increasing additions of the lubricant on both compact strength and surface area for sodium chloride is presented in Fig. 3.
d
oo.-
0.050
3 1000
1
E
h
G
I
2
v
OJ 0
I,
O.OOL
Rq =
,/
0.050
0.00.9
500,
OJ 0
IX
O.OOL
CONCENTRATION
0.008
OF MAGNESIUM
STEARATE
I,
been obtained for silica compacts [23], where only a small amount of adsorbed water decreases the compact strength considerably, whereafter the strength remained fairly constant when the adsorption of water was further increased. One possible interpretation of the data obtained could be that two different bond types are involved in the interparticulate attraction. One bonding mechanism (e.g., molecular forces of Van der Waals type) could then be very sensitive for surface changes, while the other mechanism (e.g., solid bridges due to ionic bonding) could be established even in the presence of a lubricant film by, for example, a penetration by point irregularities. When a total surface coverage of sodium chloride particles by magnesium stearate is obtained, the latter bond type alone would determine the compact strength. In order to calculate the fraction R, of the external surface area that is covered by magnesium stearate ‘particles’, the following approximate equation could be used [ 241:
0.050 ,W,war
Fig. 3. The effect of lubricant concentration on compact strength and surface area for sodium chloride, compressed at 150 MPa.
Using minute additions, the compact strength decreased strongly with increasing magnesium stearate concentrations. This is in agreement with results reported earlier [8, 9, 213, where this effect was explained in terms of the formation of a lubricant film around the compound particles. However, at additions in excess of approximately 0.005 wt.%, the compact strength levelled off and even the use of a relatively high concentration (0.05 wt.%) gave no further reduction in strength. Similar profiles have
f3 &
1
(1 -f3)%m ; Assuming that the ratio of the surface and projected area shape coefficient (s/k) is equal to 4 [25], the surface area fraction for an addition of 0.005 wt.% magnesium stearate having a specific surface area of 2.3 m2/g (see the Table) is only 0.00288. To obtain a total surface coverage, corresponding to an R, of unity, a specific surface area of not less than 800 m2/g would be needed. This corresponds to a’particle’ size of magnesium stearate of the order of 50 - 100 a [26]. The small amount needed to reach the plateau therefore probably corresponds to the formation of a monomolecular film around the sodium chloride particles [ 211. As evident from Fig. 3, the admixture of the different lubricant amounts did not affect the powder surface area as characterized by the gas adsorption technique. However, the gas adsorption surface area of the corresponding compacts showed a decrease with increased quantities of lubricant. This effect was not expected, considering the obtained decrease in compact strength, which was supposed to expose the surface area used for
208
bonding. It was therefore not meaningful to apply the extrapolation procedure described by Stanley-Wood and Shubair [ 151. The result could probably be explained by a reduction in particle fragmentation and crack formation in the systems containing lubricant additions. Similar observations have been reported earlier [ 171. The results therefore indicate that the surface area used for bonding is relatively small, and masked by the surface area changes due to fragmentation and crack formation. The compact surface area as measured by permeametry shows an increase with lubricant addition, This result is probably due to an increased error at increasing lubricant concentrations. The equation used for the calculation of permeametry surface area does not seem to be valid for dense, low-porous compacts, as discussed for the results in Fig. 2. It was observed that the addition of magnesium stearate slightly decreased the compact porosity, which then would produce a further overestimation of the measured surface area.
Effect of ageing time on compact surface area The results in Figs. 2 and 3 have clearly demonstrated that it is difficult to obtain absolute measures of compact surface area for dense compacts by permeametry. However, the permeability measurements of sodium chloride compacts seemed to be very sensitive to small changes in compact porosity, as demonstrated for compacts containing varying amounts of lubricant (Fig. 3). Unfortunately, these changes in porosity were probably not due to changes in bonding surface area, but reflected a change in the packing ability of the sodium chloride particles. In order to utilize the sensitivity of the permeametry for the detection of bonding surface area, the technique was applied for the monitoring of surface area with ageing time of compacts. Results for both compact strength and permeametry surface area are presented in Fig. 4. Ageing time here means the waiting time between compaction and compact characterization, The compact strength was almost doubled within a few minutes. Such effects have been frequently reported for sodium chlor-
i a
:i____+i, 0
i 10
20 TIME
30
1500
lmtni
5 0.
Fig. 4. The effect of ageing time on compact strength (0) and compact surface area as measured by permeametry (0) for sodium chloride, compressed at 150 MPa. Error bars represents the 95% confidence interval for the mean.
ide [22]. The compact surface area as measured by permeametry, on the other hand, remained practically constant with ageing time [16]. It seems therefore that the increase in the bonding surface area, as reflected by the increase in compact strength, is either small or could not be detected by permeametry. In relation to the results discussed earlier (Figs. 2, 3), the most probable explanation seems to be that the bonding surface area is too small to be detected. However, it could not be excluded that the increase in compact strength with time (Fig. 4) could be due to two bonding mechanisms. The initial strength would then be due to one bond type, followed by a time-dependent increase in strength due to a continous formation of bonds of the second type. This second bonding mechanism must then be active over relatively long distances (e.g., Van der Waals forces) in order to explain why the compact permeability will not be decreased when these bonds are established. The time-dependency could be due to plastic flow caused by stress relaxation, bringing surfaces into closer proximity.
CONCLUSIONS
The results obtained demonstrate the problems involved when investigating the compaction behaviour of pharmaceutical materials. Although sodium chloride in pharmaceutical studies [8, 9, 141 normally represents a nearly ideal model substance (non-porous and consolidating by plastic deformation), it is evident from the present study that sodium chloride must be classified
209
as a complex substance with respect to its compaction behaviour. In contrast to the iron powder, sodium chloride particles undergo such changes during compression (fragmentation and formation of cracks and pores) that a simple monitoring of changes in surface area with pressure (Fig. 2) cannot unambigously be used for the evaluation of bonding surface area. Considering the even more complex nature of most pharmaceutical materials used in some reported studies [8, 12 - 151 it is questionable whether the interpretations suggested, purporting relatively high bonding surface areas [ 12 - 151, are justified solely on the basis of previously published experimental data. The results in the present study indicate that the surface area taking part in the interparticulate attraction for sodium chloride, as well as for iron powder, is small in relation to the geometrical surface area available. It cannot be excluded that bonding is facilitated by long-range forces (e.g., molecular forces of the Van der Waals type), thereby explaining why the two surface area techniques are not capable of detecting any substantial change in bonding surface area with changes in the different parameters tested.
ACKNOWLEDGEMENTS
The authors are very grateful to Mr. B. Johansson for skilful technical assistance and to Mrs. Eva Nises Ahlgren for preparing the manuscript. One of us (C.N.) is grateful to the Swedish Academy of Pharmaceutical Sciences for financial support.
LIST OF SYMBOLS
weight fraction of fine material (lubricant) in the binary mixtures k projected area shape coefficient surface fraction of coarse material 8 (sodium chloride) covered by the fine material SWC weight specific surface area of coarse material, mz g-l
f3
swf oc,
weight specific surface material, m2 g-r surface shape coefficient
area of fine
REFERENCES 1 J. A. Hersey, G. Bayraktar and E. Shotton, J. Pharm. Pharmacol. Suppl., 19 (1967) 24s. J. Pharm. Pharma2 E. Shotton and D. Ganderton, col. Suppl, 13 (1961) 144 T. 3 G. AIderborn and C. Nystriim, Acta Pharm. Suet., 19 (1982) 381. 4 J. Lazarus and L. Lachman, J. Pharm. Sci., 55 (1966) 1121. 5 G. Alderborn and C. Nystrom, Acta Pharm. Suet., 19 (1982) 147. 6 R. W. Heckel, Trans. Metall. Sot. AIME, 221 (1961) 671. I R. W. Heckel, Trans. Metall. Sot. AIME, 221 (1961) 1001. 8 M. Duberg and C. Nystriim, Acta Pharm. Suet., 19 (1982) 421. 9 A. H. de Boer, G. K. Bolhuis and C. F. Lerk, Powder Technol., 25 (1978) 75. 10 M. Duberg and C. Nystrom, Znt. J. Pharm. Technol. Prod. Mfr., in press. 11 F. P. Bowden and D. Tabor, The Friction and Lubrication of Solids, Oxford University Press, New York, 1950. 12 T. Higuchi, A N. Rao, L. W. Busse and J. V. Switosky, J. Am. Pharm. Assoc., Sci. Ed., 42 (1953) 194. 13 J. S. Hardman and B. A. LiIIey, Proc. R. Sot. Lond., A333 (1973) 183. Powder 14 N. A. Armstrong and R. F. Haines-Nutt, Technol., 9 (1974) 287. 15 N. G. Stanley-Wood and M. S. Shubair, Powder Technol., 25 (1980) 57. 16 G. AIderborn, M. Duberg and C. Nystrom, Powder Technol., 41 (1985) 49. and R. F. Haines-Nutt, Proc. 17 N. A Armstrong 1st. Znt. Conf Compaction Consol. Part. Matter, 19 72, Brighton, Powder Advisory Centre, London, 1974, p. 161. 18 G. AIderborn and C. Nystrom, Powder Technol., 44 (1985) 37. 19 J. T. Fell and J. M. Newton, J. Pharm. Sci., 59 (1970) 688. 20 J. Chyssler and B. Gronroos, Workreport BP78/l 7, AB Atomenergi, Studsvik, S-611 01 Nykoping, Sweden. 21 G. K. Bolhuis, C. F. Lerk, H. T. Zijlstra and A H. de Boer, Pharm. Weekblad, 110 (1975)317. 22 J. E. Rees and E. Shotton, J. Pharm. Pharmacol. suppz., 22 (1970) 17. 23 D. Dollimore and G. R. Heal, J. Appl. Chem., 11 (1961) 459. 24 C. Nystriim, J. Mazur and J. Sjiigren, Znt. J. Pharm., 10 (1982) 209. 25 T. Allen, Particle Size Measurement, Chapman and Hall, London, 2nd edn., 1974, p. 202. 26 T. Allen, Particle Size Measurement, Chapman and Hall, London, 2nd edn., 1974, p. 80.