Kollidon® CL

Kollidon® CL-F
Kollidon® CL-SF
Kollidon® CL-M
Super-disintegrants and dissolution enhancers.
2 The Preface

New: 4 dimensions of
Kollidon® CL – standard,
fine (CL-F), superfine (CL-SF)
and micronized (CL-M) for
your individual needs.
Kollidon® is well known as a
universal excipient range since
more than 60 years.
Kollidon® CL, the cross-
linked PVP, is not only one of
the three “super-disintegrants”.
Moreover, Kollidon® CL accel-
erates the dissolution and the
bioavailability due to its power
to form complexes with many
insoluble actives.
The disintegration of a tablet can
be regarded as the initial step in
terms of bioavailability and phar-
macological action of the active
substance. To achieve rapid disin-
tegration, a disintegrant normally
has to be added to the tablet for-
mulation. The insoluble grades of
Kollidon® are widely used in the
pharmaceuticals industry for this
purpose. Furthermore, their use
as pharmaceutical excipients is
triggered by their ability to hydro-
philize insoluble drugs, to stabilize
suspensions and to form com-
plexes, as well as by their adsorp-
tive properties.
BASF supplies Kollidon® CL,
Kollidon® CL-F and Kollidon®
CL-SF as disintegrants for the
pharmaceutical industry.
Kollidon® CL-M is usually used
as a suspension stabilizer.

Trademarks are owned

by BASF Aktiengesellschaft

Dissolution of acetylsalicylic acid tablets

100

90

80
+ 3 % Kollidon® CL
70
dissolved drug [%]

60

50

40

30

20 without Kollidon® CL

10

0
0 10 20 30 40 50 60

time [min]

water
Over the past few years, there
has been a trend towards highly
potent actives (HPAPI) and, as
a consequence, a trend towards
smaller tablets. The growth rate
of 19 % for HPAPIs underlines
the strong market need for po-
tent disintegrants for these ap-
plications. These smaller tablets
usually require disintegrants of
much smaller particle size to
guarantee content uniformity and
to prevent the tablets from show-
water
water
ing rough surfaces after storage.
The disintegrants, however, still
require the power sufficient for a
rapid disintegration. Scientific in-
vestigation has indicated that the
disintegration power decreases
with decreasing particle size. This
can be confirmed by testing our
new materials Kollidon® CL-F and
Kollidon® CL-SF. Although these
materials have smaller particle
sizes, they are still potent disinte-
grants.
The Preface 3
The theory of
disintegration of a tablet
1. Disintegrants are
very hydrophilic.
2. Spherical particles
are uniformly distributed
in the tablet.
3. They swell during
contact with water
or other liquids.
4. They significantly
increase volume and
disintegrate the tablet.
The Market Trends
Furthermore, in new drug delivery
technologies such as oral dispers-
ible tablets, fast disintegrants with
very good mouth feeling are in
strong demand. Many of these
drugs go into pediatric applications
and to the OTC market in general,
where good patient compliance is
a precondition for the success of a
drug formulation. Based on these
market trends, our customers will
now require new disintegrants for
their new applications.
4 The Products

The different Kollidon® CL grades In contrast to many other disinte-

can best be distinguished by their grants, the Kollidon® CL grades
different particle sizes: are non-water-soluble. As a conse-
quence, there is no influence on
Average particle size range [µm] the disintegration of a tablet and
the dissolution of the active due to
■ Kollidon® CL 110–130 the increased viscosity. The cros-
■ Kollidon® CL-F 20–40 povidones act as disintegrants by
■ Kollidon® CL-SF 10–30 absorbing water and subsequently
■ Kollidon® CL-M 3–10 swelling. This gain in volume is
responsible for the subsequent
All CL-grades are crosslinked, wa- disintegration of the tablet.
ter-insoluble polivinylpyrrolidones.
There are chemical but mainly However, the speed of disinte-
physical crosslinks. gration is not only based on the
swelling;

Chemical names it is a combination of many

factors such as:
■ Crospovidone
■ Crospovidonum ■ The swelling volume of the
■ Insoluble polyvinylpyrrolidone disintegrant
O ■ Crosslinked PVP ■ The swelling pressure of
N the disintegrant
■ The hydrophilic behavior of
the disintegrant
* ■ The pore sizes within the tablet
n* ■ The mechanical properties
of the tablet

Chemical crosslinks

Entangled polymer
chains (N-vinylpyrro-
lidone-polymer)

A highly (mainly
physically)
crosslinked
polymer matrix

The chemical structure of

Kollidon® CL: It is a cross-
linked homopolymer of
N-vinyl-2-pyrrolidone
6 The Application

In general, there is no perfect
disintegrant. Disintegration is
strongly dependent on the for-
mulation of the tablet in terms
of porosity, method of manu-
facture (wet or dry granula-
tion) and the use of different
actives and other excipients.
Comparison of the materials
The principle property of the
materials is to decrease the dis-
integration time of tablets. In the
figure below the three Kollidon
grades are compared with their
main competitive materials.
Clearly, Kollidon® CL shows the
strongest performance.
Even with a decreased particle
size, the new grades Kollidon®
CL-F and Kollidon® CL-SF show
good performance, not having
some of the drawbacks that Kolli-
don® CL has, as explained above.
Apart from the increase in tablet
disintegration, it is even more im-
portant that the dissolution of the
active ingredient is also increased.

Disintegration time of direct compressed tablets with different disintegrants

(6 % disintegrant in Ludipress® LCE, compressed at 18 kN)

02:09
01:55

01:40

01:26
time [min:sec]

01:12

00:57

00:43

00:28

00:14

00:00
Kollidon® Kollidon® Kollidon® Crospovi- Crospovi- Croscar- Sodium
CL CL-F CL-SF done done mellose- starch
Competitor A Competitor A sodium glycolate
(100–130 µm) (30–50 µm)
 The Application 7

Dissolution of acetaminophen in deionized water

(2.7 % disintegrant in a wet granulated formulation, compressed at 18 kN)

method: paddle 100 rpm; 37 °C

100

90

80

70
drug release [%]

60 ■ Kollidon® CL
■ Kollidon® CL-F
50 ■ Kollidon® CL-SF
■ Crospovidone
40 Competitor A (100–130 µm)
■ Croscarmellose-sodium
30 ■ Crospovidone
20 Competitor A (30–50 µm)
■ Sodium starch glycolate
10

0
0 10 20 30 40 50 60 70 80 90 100 110 120

time [min]

The dissolution curves show that A requirement of many customers

Kollidon® CL has the best per-
formance, followed by Kollidon®
CL-F and Kollidon® CL-SF. In
some cases customers may wish
to have a slightly slower disinte-
gration for specific applications;
the new materials could help to
produce a dissolution profile fitted
to such a requirement, e. g. for
generics.
is that the tablets show a smooth
surface after storage in multidose
containers. Because the Kollidon®
CL grades are very hydrophilic,
they tend to absorb water and thus
produce a rough surface due to
swelling. In the case of film tablets,
this might cause cracks in the film.
Tablets produced with fine materials
Kollidon® CL-F and Kollidon® CL-
SF produce a very smooth surface.
8 The Application
Kollidon® CL
Kollidon® CL
Kollidon® CL is used as the stan-
dard disintegrant for all kinds of
fast dispersible tablet formulations.
For many years, companies have
known just how well the material
performs. The main reasons for
using Kollidon® CL are the ad-
vantages provided compared to
other materials like e. g. starch or
cellulose derivatives. When used as
disintegrants, these products tend
to form highly viscous systems
when in contact with water.
.......... ..........
300 µm 50 µm
Kollidon® CL
This is in contrast to Kollidon® CL,
which is insoluble and which as a
consequence does not slow down
the dissolution of a oral dosage
form but might even increase the
release of the active ingredient. In
some cases where Kollidon® CL
does not meet the requirements of
the customers e. g. for wet granu-
lation with a large amount of sol-
vent, Kollidon® CL-F or Kollidon®
CL-SF are suitable replacements.
..........
10 µm
 The Application 9

Kollidon® CL-F

Kollidon® CL-F

Kollidon® CL-F is the perfect Capsules filled with microtablets (capsule size 00–4)
alternative when formulators are
looking for a disintegrant with 8.5 mm
strong disintegration power in 5.2 mm
combination with a smooth tablet
surface. With Kollidon® CL,
however, some problems might
23.5 mm

14.1 mm
occur when the tablet is very
hygroscopic and packed in a
multi-dose container.

.......... .......... ..........

300 µm 50 µm 10 µm

Kollidon® CL-F

Kollidon® CL-F should be used for step where large amounts of

the development of small tablets
when fine particles are required to
avoid content uniformity prob-
lems. Furthermore, the material
is able to absorb large amounts
of solvent. This can be beneficial
when customers use such large
amounts during a wet granulation
solvent are needed e. g. for
dissolving the active.
However, in some cases,
Kollidon® CL-SF might be the
best solution for a specific
application.

Microtablets,
2 mm diameter
10 The Application
Kollidon® CL-SF
Kollidon® CL-SF
Kollidon® CL-SF has advantages
when it comes to special appli-
cations, for example oral fast dis-
persible tablets. The main reason
is reliable disintegration power in
combination with a very smooth
cream-like mouth feel. Neverthe-
less, in some cases, Kollidon®
..........
300 µm
..........
50 µm
CL-SF might be used as a regular
disintegrant when customers have
a wet granulation process that
uses large amounts of solvent.
Kollidon® CL-SF has the highest
solvent (water/ethanol etc.) uptake
capacity of all the crospovidones
produced by BASF.
Kollidon® CL-SF
..........
10 µm
12 The Examples

Formulation of Nifedipine tablets (granulated)

Nifedipine 10 mg (5.85 %)
Kollidon® VA 64 10 mg (5.85 %)
Ludipress® LCE 100 mg (58.50 %)
Kollidon® CL-F or -SF 50 mg (29.22 %)
Magnesium stearate 1 mg (0.58 %)

Tablet weight 171 mg (100 %)

Formulation of Haloperidol tablets (direct tabletting)

Haloperidol 2 mg (2.5 %)
Ludipress® LCE 75 mg (93.75 %)
Kollidon® CL 2.5 mg (3.12 %)
Magnesium stearate 0.5 mg (0.63 %)

Tablet weight 80 mg (100 %)

 The Overview 13

As far as disintegrants are con-
cerned, there are many products
in the market starting with the
basic starches derived from maize,
rice, corn and potato. They have
been used for a long time but have
certain disadvantages in terms of
the amount that is needed to
ensure disintegration. One particu-
lar disadvantage of disintegrants
based on starch and of the cellu-
lose derivatives is the increase of
viscosity after disintegration. The
first question is always related to
the real effect of the disintegrant
on the disintegration time.
In the figure, the disintegration
test results of tablets produced
with granulated material are
shown. These clearly show the
strengths of the crospovidones,
especially the Kollidon® CL
grades.

Disintegration of tablets made of granules (2,7 % disintegrant extragranular use,

compressed at 18 kN)

35
33:56
30
disintegration time [min]

25
22:37 23:28
20

15
12:46 12:30
10 11:08
08:55 09:06

0
Kollidon® Kollidon® Kollidon® Kollidon® Crospovi- Crospovi- Croscar- Sodium
CL CL-F CL-SF CL-M done done mellose- starch
Competitor A Competitor A sodium glycolate
(100–130 µm) (30–50 µm)
14 The Overview

Disintegrants on the market

Required Disinte- Hardness Issues during

% gration power of the tablets storage at
1: low high humidity
10: high

Starches 3–15 3 Low *

Starch derivatives

Sodium starch glycolate 2–8 4 High Brown spots

Cellulose derivatives

Carmellose-sodium 1–6 5 Medium *

Croscarmellose-sodium 0.5–5 7 High Brown spots

(most cases 2–3)

Carmellose-calcium 5–15 5 Medium *

HPC 5–25 5 High *

Crospovidone grades

Compet. A (100–130 µm) 2–5 8 High Rough surface

Compet. A (30–50 µm) 2–5 7 High Smooth surface

Kollidon® CL 2–5 9 Medium Rough surface

Kollidon® CL-F 2–5 8 High Smooth surface

Kollidon® CL-SF 2–5 7 Very high Smooth surface

*: Not tested
 The Summary 15

The following table describes ceutical industry and their

the advantages of each material customers, the patients.
for our customers – the pharma-

Benefits for manufacturers Benefits for patients Main applications

Kollidon® CL The super-disintegrant, Fast drug absorption Disintegrant for

very fast disintegration for most APIs standard tablets

Kollidon® CL-F No content uniformity Easy to swallow Small tablets,

problems especially in due to tablet size tablets stored under
small tablets high humidity

Kollidon® CL-SF Perfect for fast Best mouthfeel Fast dispersible

dispersible tablets, tablets,
excellent tablet surface intragranular
disintegrant for
wet granulation

Kollidon® CL-M Stable dispersions Easy to redisperse Suspensions

Depending on the preferred disintegration and dissolution rate, our customers

can select the excipient of choice from our comprehensive product range.
 Please write Please
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apply
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postage
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Company

Address

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Country BASF
Aktiengesellschaft
Telephone G-MEP/ME – Li 554
Attn: Dr. Hubertus Folttmann
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e-Mail Germany

Fax Reply

Local contact:

or Headquarter Germany:

+49-621-60-2 86 40

Please complete, copy and fax to us,

or detach the postcard and send it to us.

Please send the ■ Technical information

following information: on Kollidon® VA 64.

■ Technical information on ■ Technical information

Kollidon® CL grades. on Kollidon® VA 64 Fine.

■ Sample of ■ Technical information on

Kollidon® CL, 0.5 kg.
■ Sample of
Kollidon® CL-F, 0.5 kg.
■ Sample of
Kollidon® CL-SF, 0.2 kg.
■ Sample of
Kollidon® CL-M, 0.5 kg.
Ludipress®.
■ DVD “Pharmaceutical Excipients
by BASF Fine Chemicals”.
■ Newsletter “ExAct”
(Excipients & Actives for Pharma).

■ Please contact me, I would

like to know more about
Kollidon® CL.
Please send the ■ Technical information
following information: on Kollidon® VA 64.

■ Technical information on ■ Technical information

Kollidon® CL grades. on Kollidon® VA 64 Fine.

■ Sample of ■ Technical information on

Kollidon® CL, 0.5 kg.
■ Sample of
Kollidon® CL-F, 0.5 kg.
■ Sample of
Kollidon® CL-SF, 0.2 kg.
■ Sample of
Kollidon® CL-M, 0.5 kg.
Ludipress®.
■ DVD “Pharmaceutical Excipients
by BASF Fine Chemicals”.
■ Newsletter “ExAct”
(Excipients & Actives for Pharma).

■ Please contact me, I would

like to know more about
Kollidon® CL.

We look forward to answering any questions you may have. Please

fill in the postcard, detach it and return it to the address overleaf.

Please contact your local BASF company or

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www.pharma-solutions.basf.com
■ Excipients ■ Actives
Kollidon® grades Cremophor ® Ephedrines
Group of povidone grades and Pseudoephedrines
and copovidone Solutol® HS 15 Theophylline
products suitable Range of different Caffeine
mainly as tablet ethoxylated Isotretinoin
binders, emulsifiers and Tretinoin
crospovidone as solubilizers Ibuprofen
tablet disintegrant suitable for topical, Dobutamine
and dissolution oral and parenteral Dopamine
enhancer. formulations. Isometheptene mucate
Kollidon® SR Soluphor ® P Oxymetazoline
Matrix sustained 2-pyrrolidone. PVP-Iodine
release polymer. Lutrol® grades Selegiline
Ludipress® grades Range of PEGs Xylometazoline
Direct tabletting (Lutrol® E range)
aids for faster and poloxamers APIs by Orgamol
product develop- (Lutrol® F range)
ment and speedier for a wide variety Vitamins
processing. of pharmaceutical
Kollicoat ® grades dosage forms. ■ Contract
Range of aqueous Manufacturing
based film formers,
cost efficient and ■ Value Added
ecological.

Pharma Solutions by BASF

BASF offers more than BASF Aktiengesellschaft

cGMP quality and supply Fine Chemicals Division
safety: technical expertise. Pharma Solutions
Our technical service is 67056 Ludwigshafen
always at your side. Germany

BASF wishes to create ■ Fax +49-621-60-2 86 40

a prosperous and sustain- ■ pharma.solutions@basf.com
able future with you as our ■ www.pharma-solutions.basf.com
customer – and partner.

BASF – the world’s leading chemical company – can look

back on well over 140 years of success and has attained an
outstanding position as a reliable partner.

Our portfolio for the pharmaceutical industry comprises a

comprehensive range of major and new active ingredients
and excipient brands.
MEMP 060401e-00