Other DFE Pharma Superdisintegrants

Product type
Primellose

Product name
Croscarmellose sodium

Product benefits
Powerfully swelling superdisintegrant
Highly effective in a very wide range of formulations

Application notes

Primojel
Superdisintegrants

Primojel is DFE Pharmas product brand name for sodium starch glycolate
(type A). Primojel complies with the requirements of the Ph. Eur., USP-NF and
JP monographs. Primojel is made in a dedicated pharmaceutical plant in Foxhol,
the Netherlands.

Chemistry and Functionality

DMV-Fonterra Excipients GmbH & Co. KG - Warranty
The details given here are merely intended for information purposes and
are in no way legally binding. Consequently we accept no responsibility
in the broadest sense of the word for d
amage that may result from
applications based upon this information. Furthermore, this information
does not constitute permission to infringe patent and licence rights.

www.dfepharma.com

#001/October 2011

Head Office
Klever Strasse 187
P.O. Box 20 21 20
47568 Goch, Germany
T. +49 2823 9288 770
F. +49 2823 9288 7799
pharma@dfepharma.com

Primojel is chemically cross-linked and

carboxymethylated potato starch. It is
manufactured by cross-linking starch with
sodium trimetaphosphate followed by carboxy
methylation with sodium monochloroacetate.
Approximately one glucose monomer unit in
every four is substituted. The benefits of potato
starch and the optimisation of the degrees of
cross-linking / substitution have been described

The intragranular components were wet

granulated (high shear), dried, sieved and
blended with the extragranular portion of the
Primojel and magnesium stearate. Tablets were
compressed at 250 mg and dissolution tested in
900ml of water using USP apparatus 2.

12
10
8
6
4

% diclofenac in solution

Initial

40C/75%

Spray-dried
mannitol

Pharmatose
100M/MCC

SuperTab
30GR

In Direct Compression

SuperTab
21AN

SuperTab
11SD

The recommended starting point is 2% to 4%

of Primojel. The figure shows how the
disintegration time of various placebo tablets
(250 mg / 9 mm tablets containing 4% Primojel
and 0.5% magnesium stearate) is maintained
after storage for 6 months at 40C / 75% RH in
open containers. The disintegration of reference
tablets stored for 6 months under ambient
laboratory conditions is also shown. These data
confirm that Primojel remains an effective
superdisintegrant. Tablets based on anhydrous
lactose may show prolonged disintegration on
accelerated testing, although disintegration is
maintained in the reference samples. For tablets
containing only dicalcium phosphate as the
filler, Primellose is preferred. Its higher swelling
power maintains disintegration after accelerated
storage.

chloric acid which will prevent complexation.

An example of a simple UV assay of Diltiazem
hydrochloride tablets (tablets weighing 250 mg
and containing 4% Primojel) is shown on the
right. The apparently low assay in water is
corrected by assay in 0.1 M hydrochloric acid.

Reference

In Wet Granulation
We recommend that Primojel is incorporated
at least partly (50% or more) within the granu
lation. This is especially important when a high
proportion of insoluble diluent is employed as
shown in this example which uses Diclofenac
as the API and dibasic calcium phosphate
dihydrate as the main diluent.
Component
Diclofenac sodium
Dicalcium phosphate2H2O
MCC 101

mg per tablet
25.0

25.0

25.0

25.0

25.0

5.0

5.0

5.0

Primojel (intragranular)

10.0

5.0

-----

Primojel (extragranular)

-----

5.0

10.0

2.5

2.5

2.5

Magnesium stearate
Total

100
80

250.0 250.0 250.0

120
100
80

60

60

40

40

20

20

10
20
Extragranular
Intragranular
50/50 split

30

40

50
60
Time (minutes)

Dissolution of Diclofenac is slower when the

Primojel is used only in the extragranular
phase. If lactose is used instead of dibasic
calcium phosphate, then the effect of Primojel
location is greatly reduced.

182.5 182.5 182.5

25.0

Povidone (K=25)

120

Assay (%Label)

Disintegration time (minutes)

(GK Bolhuis et al, Disintegration efficiency of

sodium starch glycolate formed from various
native starches, Eur. J. Pharm. Biopharm., 1994,
40(5), 317 320: GK Bolhuis et al, Effect of
variation of degree of substitution, cross-linking
and purity on the disintegration efficiency of
sodium starch glycolate, Acta pharm. Technol.,
1984, 30(1), 24 - 32). Primojel is manufactured
to this optimised chemistry.

With weakly basic APIs

It is well known that croscarmellose sodium may
form weak charge transfer complexes with some
weakly basic APIs. This effect may also occur, but
to a lesser extent, with sodium starch glycolate.
A consequence of this is that dosage forms
may appear to be sub-potent on analysis or
dissolution testing.
A simple solution is to ensure that dissolution
testing and extraction for analysis, is performed
using a low pH medium such as 0.1 M hydro

5 mg

15 mg

Assay in H2O

30 mg

60 mg

Assay in 0.1 M HCl