Energetické hodnocení lisovacího procesu přímo lisovatelného isomaltu
V práci je porovnávána lisovatelnost dvou přímo lisovatelných isomaltů galenIQ™ 720 a galenIQ™ 721 prostřednictvím energetického hodnocení lisovacího procesu pomocí záznamu „síla-dráha“. Jsou zde hodnoceny energie na tření, energie akumulovaná tabletou, energie dekomprese, energie lisování a plasticita, a to u čistých suchých pojiv, u suchých pojiv s mazadly (0,5 a 1% stearanu hořečnatého a stearylfumarátu sodného) a dále u tabletovin s modelovými léčivy kyselinou acetylsalicylovou a askorbovou. Z výsledků práce vyplynulo, že nižší hodnoty energie na tření i na lisování při stejné lisovací síle vykazuje látka galenIQ 720, proto je lépe lisovatelná než látka galenIQ 721.
Klíčová slova: přímo lisovatelný isomalt – záznam „síla-dráha“ – mazadla
Jitka Mužíková; Veronika Pavlasová
Authors place of work:
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Technology, Czech Republic
Published in the journal:
Čes. slov. Farm., 2011; 60, 11-16
The paper compares the compressibility of two directly compressible isomalts, galenIQ™ 720 and galenIQ™ 721, using the energy evaluation of the compaction process by means of the force--displacement profiles. It evaluates the energies for friction, energies accumulated by the tablet, energy of decompression, energy of compaction and plasticity in pure dry binders, in dry binders with lubricants (0.5 and 1% of magnesium stearate and sodium stearyl fumarate) and further in the tableting materials containing the model ingredients acetylsalicylic acid and ascorbic acid. The results of the study have revealed that lower values of the energy for friction and compaction with the identical compression force are found by the substance galenIQ 720, which is therefore better compressible than the substance galenIQ 721.
The measurement of
the force-displacement dependence is one of the most widely used methods for
the study of the compaction process in the course of tableting. It is
the dependence between the trajectory of the upper punch and the compression
force. When the upper punch is entering the matrix, the compression force is
fluently increasing; after the set value at which the compact is produced is
achieved, it rapidly decreases to the initial value. This gives rise to
a curve by means of which it is possible to describe the energetic course
of compaction (Fig. 1). The supplied energy is necessary for the compression of
materials and the formation of solid compacts. The area under the presented
curve corresponds to the work of compression, i.e. the energy accumulated in
the tablet (E2); the record makes it also possible to determine the
energy consumed by friction during compression (E1) and the elastic
component of energy (E3). The energetic profiles can be useful as
material compression characteristics in pre-formulation studies of
compression of various substances. Their contribution primarily lies in the
possibility to subsequently correlate the energetic inputs or the work of
compression with the deforming and tablet-forming properties of various
materials 1, 2).
The present paper compares, by means of energetic
evaluation of the compaction process, two types of directly compressible
isomalt, galenIQ 720 and galenIQ 721. The paper directly links up with the
previous publication, which evaluated the compressibility of both substances by
means of the strength of compacts and in this connection no more significant
difference in the compressibility of isomalts was found 3). Isomalt
is a mixture of hydrogenated monosaccharides and disaccharides and its
principal components are disaccharidic alcohols 1-O-α-D-glucopyranosyl-D-mannitol
dihydrate (GPM) and 6-O-α-D-glucopyranosyl-D-sorbitol (GPS) 4). The
agglomerated product of isomalt is produced by the German firm Palatinit GmbH
under the name of galenIQ™, types 720 and 721 being intended for
direct compression. The individual types differ by the ratio of the principal
disaccharide alcohols; in type 720 the ratio GPM and GPS is 1 : 1 and
in type 721 this ratio is 1 : 3, and as the result it is more soluble in
720 – agglomerated isomalt ( 1-O-α-D-glucopyranosyl-D-mannitol dihydrate and 6-O-α-D-glucopyranosyl-D-sorbitol in the ratio of
1 : 1) (Palatinit GmbH, Germany);
721 – agglomerated isomalt ( 1-O-α-D-glucopyranosyl-D-mannitol dihydrate and 6-O-α-D-glucopyranosyl-D-sorbitol in the ratio of
1 : 3) (Palatinit GmbH, Germany);
Tests included tableting materials from dry binders
without lubricants, mixtures with lubricants, and mixtures with active
ingredients. Altogether 18 tableting materials of the following composition
were used (Table 1 and 2).
binders with lubricants were mixed for 5 minutes in a stainless steel cube
KB 15S (Erweka GmbH, Hausenstamm, Germany). Mixtures with active ingredients
were prepared by mixing the dry binder and the active ingredient for 5 minutes,
then the lubricant was added and the material was mixed for 5 minutes again.
The rotation rate of the mixing cube was always 17 revolutions/minute. The
amount of prepared tableting materials without active ingredients was always 30
g, with active ingredients, 20 g.
Preparation of tablets and energy evaluation of compaction process
tableting materials were used to produce 10 tablets compressed with the use of
a special die with an upper and a lower punch on a material
testing equipment T1–FRO 50 TH.A1K Zwick/Roell (Zwick GmbH & Co, Ulm,
Germany). Proper compaction took place by applying the pressure on the upper
punch. The tablets were of a cylindrical shape without facets with
a diameter of 13 mm and weight of 0.5 ± 0.0010 g. Compression
velocity was 1 mm/s and compression force 8 kN. The value of preloading was 2
N, the velocity of preloading, 2 mm/s. Mixtures including active ingredients
were compressed using a compression force of 10 kN. In all tablets, the
“force-displacement” plot was drawn by means of a computer programme
testXpert V 9.01 and the compaction process was evaluated as far as energy
was concerned, i.e. the energies E1, E2, E3,
Ecomp and plasticity were expressed numerically. Energy E1 is the
energy consumed by friction, energy E2 is the energy accumulated by
the tablet in the course of compression, energy E3 is the energy
released during decompression, and Ecomp is E2 + E31).
RESULTS AND DISCUSSION
study aimed to evaluate the difference in the compressibility of two types of
directly compressible isomalts by means of the energetic evaluation of the
compaction process. The results of the study are presented in five figures and
one table. The figures and the table show the values of the energy consumed for
friction (E1), energy accumulated by the tablet after compaction (E2),
energy of decompression (E3), plasticity, and the energy of
compaction (Ecomp), which is the sum of the energy accumulated by the tablet
and the energy of decompression. The figures show these values for the dry
binders galenIQ 720 and 721 without and with lubricants at the compression
force of 8 kN. The table summarizes the values of the energies of these
substances in a mixture with the model active ingredients acetylsalicylic
acid and ascorbic acid in the ratio of 1:1
always with 1% of lubricants at the compression force of 10 kN.
2 represents the values of the energy E1 at the compression force of
8 kN for the isomalts under study. This energy is the energy consumed by
friction and its value is lower in the case of the substance galen IQ 720. The
value of this energy is slightly decreased by the lubricants. Within the type
and concentration of lubricants there is no larger difference between the
3 shows the values of the energy E2. It is the energy accumulated by
the tablet after compaction. This energy is again lower in the case of the
substance galenIQ 720. Lubricants decrease its value in the substance galenIQ
721. In the substance galenIQ 720 this energy is decreased only by a 1%
addition of Pruv.
4 represents the values of the energy E3. It is the energy released
during decompression, i.e. the energy expressing the elasticity of the
material. In this case there were no statistically significant differences in
the values of pure dry binders and the mixtures with 0.5% and 1% of
magnesium stearate. In the case of the mixture with 0.5% of Pruv and 1% of
Pruv, the values were higher
in the case of the substance galenIQ 721. The values of this energy are the
lowest, the highest values being those of the energy consumed by friction.
5 shows the values of the energy of compaction (E2 + E3).
This energy is higher in the case of the substance galenIQ 721, above all due
to a higher value of E2.
6 represents the plasticity of both isomalts; higher values are shown by galenIQ 721, plasticity in
this case decreases with an addition of lubricants.
Table 3 shows the examined values of energies and
plasticity for tableting materials containing active ingredients, viz. ascorbic
acid and acetylsalicylic acid, in the proportional representation to dry
binders of 1 : 1. The active ingredients employed differ in their mechanisms of
compaction; acetylsalicylic acid is compacted mainly plastically, ascorbic acid
by fragmentation of particles 6). In both active ingredients there
occurred a higher value of energy for friction for galen IQ 721, where, in
addition, there is no difference in the lubricant employed. In the substance
galen IQ 720, there is a lower value of energy in the mixture with 1% of
Pruv. Within the type of the active ingredient, higher values occur in the
tableting material containing acetylsalicylic acid. As concerns the value of
energy E2, i.e. that accumulated in the tablet, there are
significantly lower values of this energy in tableting materials containing the
isomalt galen IQ 720 and in the case of the mixtures containing acetylsalicylic
acid, which is better compressible. In addition, it reveals the difference within
the type of the lubricant, which is more marked in the case of ascorbic acid.
The values of E2 are always higher with 1% of magnesium stearate.
The values of the energy of decompression are higher in the case of the
tableting materials containing acetylsalicylic acid, due to the prevailing
mechanism of compression by plastic deformation 6). The difference
in the effect of lubricants is not statistically significant in the case of
both active ingredients. The value of the energy of compaction (E2 +
E3) is higher in the case of both active ingredients for galenIQ
721. The values of plasticity are again higher in the case of the substance
galenIQ 721 in both active ingredients, in the case of mutual comparison of the
active ingredients surprisingly in the mixtures with ascorbic acid, which
should be less plastically deformable.
can be concluded that lower values of energy for both friction and compaetion
are found in the dry binder galenIQ 720, which is therefore from
the energy standpoint better compressible than galenIQ 721.
The study was supported
by the grant MSM 0021620822 and by the firm PALATINIT GmbH Germany, which
supplied the samples of the dry binders tested.
5 January 2011
Accepted 15 January 2011
PharmDr. Jitka Mužíková, Ph.D.
Department of Pharmaceutical Technology,
Charles University in Prague
Faculty of Pharmacy in Hradec Králové
Heyrovského 1203, 500 05 Hradec Králové
1. Ragnarsson, G.: Force-diplacement and network measurements. In Alderborn, G., Nyström, Ch., eds. Pharmaceutical powder compaction technology, Inc. New-York: Marcel Dekker 1996; 177–197.
2. Komárek, P., Rabišková, M.: Technologie léků. 3. vyd. Galén: Praha 2006; 228–240.
3. Mužíková, J., Pavlasová, V.: A study of the properties of tablets from directly compressible isomalt. Čes. slov. Farm. 2009; 58, 172–178.
4. Bolhuis, G. K., Armstrong, N. A.: Excipients for direct compaction – an update. Pharm. Dev. Tech. 2006; 11, 111–124.