A Novel Copovidone Binder for Dry Granulation and

A Novel Copovidone Binder
for Dry Granulation and
Direct-Compression Tableting
Antonio Moroni
Plasdone S-630 copovidone, a
synthetic random copolymer of
vinyl pyrrolidone and vinyl
acetate, has been developed for
use as a binder in pharmaceutical
tableting. Vinyl acetate in the
formulation makes the polymer
more plastic and less hygroscopic
than standard Plasdone
homopolymers without
compromising its solubility in
water.These properties make
Plasdone S-630 copovidone a dry
binder that is effective at a lowuse
level and a suitable material
for applications in dry
granulation and directcompression
tableting.
Antonio Moroni, PhD, is the manager
of pharmaceutical research at International
Specialty Products, 1361 Alps Rd., Wayne,
NJ 07040, tel. 973.628.3346, fax 973.628.
3759, e-mail amoroni@ispcorp.com, www.
isp-pharma.com.
Direct compression and, to some extent, dry granulation
are becoming increasingly popular methods in
the manufacture of tablets because they are easier and
quicker techniques than wet granulation. To ensure
tablets are produced with acceptable hardness and low friability,
a component with good dry-binding properties usually is
necessary in the formulation. Most dry binders consist of highly
compressible fillers or filler binders, which improve the binding
capacity of the active and make up a significant proportion
of the tablet weight. In some cases, high-performance dry binders
that do not appreciably add to the tablet weight are required,
e.g., with high-dose drugs or to improve the performance of
filler binders. Under these circumstances, the binder must be
finely divided and have exceptional powder-flow properties to
ensure ideal distribution, particularly in direct compression.
Physical and chemical properties
Plasdone S-630 copovidone is a synthetic random copolymer
consisting of N-vinyl-2-pyrrolidone and vinyl acetate in a 60:40
ratio (see Figure 1). This material comes as a freely flowing,
water- and alcohol-soluble, spray-dried powder that is mainly
composed of spherical particles (see Figure 2) (1).
The copovidone has been designed to have good plasticity,
relatively low glass-transition temperature (T g 105–108 C),
and low hygroscopicity. In addition, the material has been shown
to absorb as much as three times less water than povidone at a
given relative humidity (see Figure 3).
( CH 2 —CH ) n
Plasdone S-630
(CAS#: 25086-89-9)
( CH 2 —CH ) m
8 Pharmaceutical Technology DRUG DELIVERY 2001 www.pharmtech.com
N
O
O
C
O
CH 3
Figure 1: Chemical structure of Plasdone S-630 copovidone. MW
50,000 Da, K value 25–34, polydispersity 3.5, T g 105–108 C,
spherical particle morphology, mean particle size 95 m.

Figure 2: SEM micrography of Plasdone S-630 copovidone.
The copovidone’s flowability, hygroscopicity, and plasticity
make it a highly suitable excipient for hard-to-compress or
moisture-sensitive drugs and may improve storage stability.
Figure 4 shows its compressibility in comparison with other
direct-compression binders.
This material is listed in several pharmacopeia under the following
nomenclature:
● Copovidone NF (draft published)
● Copolyvidonum Ph Eur
● Copolyvidon DAB
● Copolyvidone JSPI
Applications
The physical properties of Plasdone S-630 copovidone (flowability,
hygroscopicity, spherical particle shape, binding strength,
glass-transition temperature, and hydrophobic–hydrophilic
balance) may offer significant advantages in the roller-compaction
and direct-compression processes involved in pharmaceutical
tablet manufacturing. The copovidone can be used
separately or in combination with lactose, dicalcium phosphate
(DCP), and microcrystalline cellulose (MCC) as a dry binder
in the roller-compaction process to produce granules with good
flow and bulk density. The product also can be used to make
effervescent tablets by direct-compression techniques, instead
of the use of solvent-based anhydrous wet granulation. The
material is water soluble and will produce a clear liquid upon
dissolution.
The properties of Plasdone S-630 copovidone were evaluated
in a study targeted to assess the compressibility of Plasdone
S-630 copovidone–based tablet formulations both in
roller compaction and direct compression. Two factors were
studied: the effect of the presence or absence of a filler or binder
(MCC) and the tableting properties in the presence of both
water-soluble (e.g., directly compressible [DC] lactose) and insoluble
(e.g., DCP) fillers, thus comparing hydrophobic and
hydrophilic excipients.
Experimental conditions
Directly compressed formulations. Hydrochlorothiazide (HCTZ)
was used as a model drug for eight different formulations. Table
I lists the components of the formulations and their percentages.
Formulations were either directly compressed or roller
compacted, granulated, and then compressed.
% Moisture
100
80
60
40
20
Plasdone K-29/32
Plasdone S-630
0
0 20 40 60 80 100
% Relative humidity
Figure 3: Moisture absorption profiles of Plasdone S-630 copovidone
and povidone.
Hardness (kp)
50
40
30
20
10
0
Roller-compacted formulations. HCTZ and acetylsalicylic acid
(ASA) were used as model drugs for roller-compacted formulations.
Table II lists the components of the HCTZ formulations
and their percentages, and Table III lists these for the ASA
formulations.
Roller-compacted formulation ribbons were prepared as
described in Table IV to evaluate, in addition to the binder
type, the effect of the roller-compaction factors on the final
tablets’ performances through a fractional factorial experimental
design. Tableting was performed in a rotary press
(Stokes, Bristol, PA) at compression forces of 6000 lbs (1 lb
force 4.448 N). Tablets were subjected to various physical
tests, including tests to evaluate hardness, friability, disintegration,
and dissolution.
Results and discussion
Directly compressed formulations. Initial formulations were prepared
keeping MCC fixed at 18% and using Plasdone S-630
copovidone at either 0% or 10% levels. As levels of copovidone
were increased, the formulation was compensated with decreasing
amounts of filler (lactose or DCP) while maintaining
the level of MCC. The following results were obtained (2):
2000 4000
Compression force (lb)
6000
Plasdone S-630 MCC Lactose DT
HPMC 15 cps Dicalcium phosphate
Figure 4: Compressibility profiles of Plasdone S-630 copovidone and
other binders.
Pharmaceutical Technology DRUG DELIVERY 2001 9

Table I: HCTZ directly compressed formulations.
Component Percentage Range (% w/w)
Hydrochlorothiazide (HCTZ) 25
MCC 101 18–28
DC lactose or dicalcium phosphate 44–54
Plasdone S-630 copovidone 10–0
Polyplasdone crospovidone XL 2
Colloidal silicon dioxide 0.5
Magnesium stearate 0.5
Total 100
Table III: ASA roller-compacted formulations.
Component Percentage Range (% w/w)
Acetylsalicylic acid (ASA) 80
Binder (Plasdone S-630 copovidone,
HPMC 15 cps, MCC 101) 5
DC lactose filler 10
Polyplasdone crospovidone XL 3
Colloidal silicon dioxide 1
Magnesium stearate 1
Total 100
● Hardness. Higher levels of Plasdone S-630 copovidone led to
a marginal increase in tablet hardness when DC lactose was
used. Tablets formulated with DCP had a greater increase in
tablet hardness.
● Ejection force. Ejection force was reduced in formulations
that contained Plasdone S-630 copovidone.
● Friability and disintegration. Marginal improvements were
observed in formulations that contained Plasdone S-630
copovidone and DCP or DC lactose.
● Dissolution. Increasing the level of Plasdone S-630 copovi-
(a) DC Lactose filler (b) DCP filler
Hardness (KPa)
20
15
10
5
S-630 10%
No S-630
0
0 2000 4000 6000 8000
Compression force (lb)
Table V: Hardness of HCTZ and ASA tablets compressed at 6000 lb
from roller-compacted formulations.*
Plasdone S-630 copovidone MCC HPMC 15 cps
Drug 4 rpm 8 rpm 4 rpm 8 rpm 4 rpm 8 rpm
HCTZ 6.7 5.7 4.7 4.4 5.4 5.2
ASA 6.9 6.5 6.8 6.1 6.9 6.4
* Values are shown for roll speeds of 4 and 8 rpm.
Hardness (KPa)
20
16
12
8
4
S-630 10%
No S-630
Table II: HCTZ roller-compacted formulations.
Component Percentage Range (% w/w)
Hydrochlorothiazide (HCTZ) 76.5
Binder (Plasdone S-630 copovidone,
HPMC 15 cps, MCC 101) 5
DC lactose filler 15
Polyplasdone crospovidone XL 2
Colloidal silicon dioxide 0.5
Magnesium stearate 0.5
Total 100
Table IV: Roller compaction factors.
Factor Low Level High Level
Feed-screw rate (rpm) 8 24
Roll speed (rpm) 4 8
Roll pressure (ton) 1 2
done from 0% to 10% did not alter the dissolution profiles
of tablets formulated with DC lactose or DCP. All formulations
passed the USP dissolution tolerance criteria.
Figure 5 shows the hardness profiles of tablets containing 0%
or 10% Plasdone S-630 copovidone substituting filler.
A second set of formulations then was prepared keeping filler
level constant (DC lactose or DCP) but substituting as much
as 10% MCC with Plasdone S-630 copovidone. The goal was
to compare these formulations directly with those containing
MCC.
The following results were obtained:
● Hardness. Tablets formulated with DC lactose and those formulated
with DCP were as hard or harder when Plasdone S-
630 copovidone was used in place of 10% MCC.
● Disintegration. Disintegration times were less than 1 min for
all tablets at all compression forces,
and no significant differences were
observed in dissolution profiles
among concentrations at 30 min.
0
0 2000 4000 6000 8000
Compression force (lb)
Figure 5: Hardness of directly compressed HCTZ formulations in which Plasdone S-630 copovidone has
replaced 10% filler for (a) DC lactose filler and (b) DCP filler.
Figure 6 shows the tablet responses
measured at 0% and
10% concentration levels of the
Plasdone S-630 copovidone,
keeping MCC levels at 28% and
18% respectively.
From these results, it appears
that the addition of Plasdone S-
630 copovidone (as much as 10%)
to formulations can improve hardness,
lower ejection force, and reduce
friability without loss in dissolution
performance. MCC can
be partly substituted by Plasdone
S-630 copovidone to achieve enhanced
compressibility, and thus
it can be used as a direct-compression
binder aid for the augmentation
of tablet characteristics.
Roller-compacted formulations.
Roller-compacted formulations
10 Pharmaceutical Technology DRUG DELIVERY 2001 www.pharmtech.com

(a) DC Lactose filler (b) DCP filler
Hardness (KPa)
Ejection force (lb)
20
15
10
5
S-630 10%MCC 28%
MCC 28%
0
0 2000 4000 6000 8000
Compression force (lb)
100
80
60
40
20
0
S-630 10%MCC 18%
MCC 28%
0 2000 4000 6000 8000
Compression force (lb)
Hardness (KPa)
(c) DC Lactose filler (d) DCP filler
Ejection force (lb)
(e) DC Lactose filler (f) DCP filler
Friability (%)
4
3
2
1
S-630 10%MCC 18%
MCC 28%
Friability (%)
20
15
10
5
S-630 10%MCC 18%
MCC 28%
0
0 2000 4000 6000 8000
Compression force (lb)
100
80
60
40
20
0
S-630 10%MCC 18%
MCC 28%
0 2000 4000 6000 8000
Compression force (lb)
0
0
0 2000 4000 6000 8000 0 2000 4000 6000 8000
Compression force (lb)
Compression force (lb)
3
2.5
2
1.5
1
0.5
S-630 10%MCC 18%
MCC 28%
Figure 6: Characteristics of directly compressed HCTZ formulations in which Plasdone S-630 has
replaced 10% MCC: hardness of HCTZ tablets for (a) DC lactose filler and (b) DCP filler; ejection force of
HCTZ tablets for (c) DC lactose filler and (d) DCP filler; and friability of HCTZ tablets for (e) DC lactose
filler and (f) DCP filler.
% Dissolved
120
100
80
60
40
20
Plasdone S-630
HPMC 15 cps
MCC
0
0 20 40
Time (min)
60 80
Figure 7: Dissolution profiles of roller-compacted ASA formulations
(6000 lb, 4 rpm) with 5% of Plasdone S-630 copovidone, MCC 101, or
HPMC 15 cps binder.
were prepared at higher drug loading,
and the binding performance
of Plasdone S-630 copovidone was
compared with those of commonly
used binders such as MCC
or hydroxypropylmethyl cellulose
(HPMC) 15 cps.
Results obtained show the following
trends (3):
● Effect of compaction parameters
on final tablet hardness. The
use of a lower roll speed produced
harder tablets with both
drugs, a confirmation of the
plastic behavior of the three
binders. Feed-screw rate and roll
pressure did not have a significant
effect on final hardness.
● Hardness. As shown in Table V,
HCTZ tablets made with Plasdone
S-630 copovidone show a
substantially improved hardness
in comparison with tablets
made with HPMC or MCC.
ASA tablets made with Plasdone
S-630 copovidone showed similar
hardness to tablets made
with both MCC and HPMC 15
cps.
● Dissolution. HCTZ tablets made
with all three binders showed
similar dissolution profiles. ASA
tablets made with MCC showed
slower dissolution profiles than
did tablets made with either
Plasdone S-630 copovidone or
HPMC 15 cps (see Figure 7).
Conclusion
Plasdone S-630 copovidone has been shown to be a good rollercompaction
binder, and its addition to directly compressed formulations
has been shown to improve tablet hardness substantially.
Tablets made with Plasdone S-630 copovidone show
higher hardness and/or better drug dissolution profiles than
those made with other binders. For additional information
about Plasdone S-630 copovidone, contact the author.
References
1. ISP technical bulletin, Pharma/PLASS630.0800.
2. A. Moroni, M. Nerella, and G. DuBrowny, “Plasdone S-630 as High-
Performance Binder for Dry Granulation,” presented at the 2000 AAPS
meeting, Indianapolis, Indiana, 29 October–2 November 2000.
3. A. Moroni, M. Nerella, and G. DuBrowny, “Plasdone S-630 Mixes as
Dry Granulation Binders with Improved Performance,” presented at
the AAPS Pharmaceutical Congress of the Americas, Orlando, Florida,
24–29 March 2001. PT
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