Journal of Intellectual Property Rights

Vol 13, November 2008, pp 601-604

Analysis of Patents Pertaining to Superdisintegrants used in Tablet Manufacturing
Mrudula H Bele and Dilip V Derle
NDMVPs College of Pharmacy, Gangapur Road, Nasik, Maharashtra 422 002
Received 19 October 2007, revised 3 October 2008
The objective of the present investigation is application of patent analysis tool in planning research on superdisintegrants in
pharmaceutical tablets. Tablet disintegration has received considerable attention as an essential step in obtaining fast drug
release. The major function of the disintegrants is to appose efficiency of the tablet binder and physical forces that act under
compression to form the tablet. Superdisintegrants generally are used at low level in solid dosage form, typically 1-10% by
weight relative to the total weight of the dosage unit. They are important in formulation of novel tablet dosage forms like mouth
disintegrating tablets. Not all research gets published in papers and a lot of information is made available to the public through
patents. A detailed analysis of the granted patents as well as patent applications can provide information that may otherwise be
found critical however, missing. By analysing patents on superdisintegrants, research gaps can be identified and the research
work to be taken up can be focused. A complete analysis of the patents granted on superdisintegrants was done using various
criteria such as patenting trends over the years, country wise distribution and different classes of superdisintegrants.
Keywords: Patent analysis, superdisintegrants, activity index

Scientists in research institutions and academics often
come across the scientific literature in peer reviewed
journals. However, this literature at times tends to
provide insufficient objective information on the
technological strategies being adopted by the
commercial companies in their research laboratories.
This is because of the fact that technologies during
their development phase are often protected by
proprietary secrecy and are least visible.
A systematic analysis of patents may provide some
of the missing information. It provides a unique
planning resource for managing R&D projects. One
potential use of patent trend data is in evaluating the
technological importance of a particular concept,
process or product and their improvements.
Consequently, in R&D programmes, the research
approach should be seriously compared with others in
terms of uniqueness, cost effectiveness and market
acceptance. Systematic examination of other patents
in the same research area can help in making this
comparison.
Patent analysis can lead to a better awareness and
improved effectiveness of creative ideas and R&D
resource allocation. Patent information is priceless.
Patent compromise vast information resource being
filed across the world in every area of technology.
Patent information enhances business intelligence of
an individual by insuring that time; efforts and
resources are not wasted in duplicating already
available research. This information also helps in
keeping a close watch on competitors. It gives an
indication of new developments and provides an
insight into the R&D trends worldwide.
Patents in superdisintegrants were analysed to gain
an understanding of the technical approaches taken by
different research groups throughout the world doing
research in the same area. Patent information on the
use of superdisintegrants is a tool for collection of
data on the trends in the latest technologies and R&D
trends worldwide in the field of use of
superdisintegrants. This information helps to analyse
the collected data in a global perspective.
1

Technological Significance of Superdisintegrants
Although compressed tablets have been
manufactured for more than 100 years and today are a
single most widely used dosage form for the
administration of drugs, systematic study of tablet
disintegration and dissolution is about 25 years old.
2-6

Disintegrants are substances or mixture of substances
added to the drug formulation that facilitate the
breakup or disintegration of tablet or capsule content
into smaller particles that dissolve more rapidly than
in the absence of disintegrants.
6
Tablet disintegration
has received significant attention as an essential step
in obtaining rapid drug release. The emphasis on
_______________
Email: Corresponding author: mrudulabele2002@yahoo.co.in
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602
availability of a drug highlights importance of
relatively rapid disintegration of a tablet as a criterion
for ensuring uninhibited drug dissolution behaviour.
Several factors affect the disintegration behavior of
tablets.
7,8,9

The major function of disintegrants is to appose
efficiency of the tablet binder and physical forces that
act under compression to form the tablet. Stronger the
binder, more effective must be the disintegrating
agents in order for the tablet to release its medication.
Ideally, it should cause the tablet to disrupt, not only
into the granules from which it was compressed, but
also into powder particles from which the granulation
was prepared.
10

In the past, starch was one of the most widely used,
inexpensive, and effective tablet disintegrant.
However, a high concentration of starch is needed to
bring about effective disintegration. The research
carried out by several scientists has helped develop
certain compounds as disintegrating agents with
efficient disintegrating properties at low
concentrations.
8,11-13

Superdisintegrants generally are used at low level in
solid dosage form, typically 1-10% by weight relative to
the total weight of the dosage unit. Selecting appropriate
formulation excipients and manufacturing technology
can obtain the design feature of fast disintegrating
tablet.
14,15
Examples of superdisintegrants are
Crosscarmelose, Crospovidone and sodium starch
glycolate which are a crosslinked cellulose, crosslinked
polymer and crosslinked starch respectively. Apart from
these three popular superdisintegrants there are some
other substances such as, ion exchange resins, gums and
soy polysachharides which are also available.
16
The
superdisintegrant may be used alone or in combination
with other superdisintegrants. Commercially available
superdisintegrants are listed in Table 1.
17

The superdisintegrant is present in the tablet in an
amount of upto 10% by weight. The superdisintegrant
may be a single superdisintegrant or a combination of
superdisintegrants and is normally used in
combination with one or more common disintegrants.
There is no particular upper limit regarding the
amount of superdisintegrant as long as the mechanical
properties of the tablet are compatible with its
intended use. However, normally amount of
superdisintegrant should not exceed 25% by weight.
From the cost point of view, amount of
superdisintegrant should not preferably exceed
15-20% by weight, as normally no particular benefits
will be achieved beyond this range.The
superdisintegrant may be present as an extra granular
and/or as an intragranular component.
18,19

Data and Methodology
Data for analysis was obtained from the patent
database maintained by National Informatics Centre
(NIC), New Delhi, as well as USPTO.

This database
consists of patent filed and granted in sixty-five
countries in wide variety of fields. Patent search was
made in both the databases for the years 1985 to 2006
using the keyword superdisintegrants.
20-25
A total of
45 patents were obtained from NIC database and
35 from the USPTO database of which 28 patents
were found common in both the databases.

Growth of Patents over the Years
The output of patents during 1983 to 2006 was
divided into 6 blocks (Table 2). The number of
patents on the use of superdisintegrants increased in
every block. Further, it was seen that Europe has
major number of patents related to the use of
superdisintegrants. Until today, 52 patents have been
filed, out of which 20 are filed by Europe.
No. of patents filed with country wise-distribution
is: Europian Union (20), United States (9), World
patents (6), Australia (4), China (5), Canada (2) and
other countries (6). These figures indicate that
maximum patents on superdisintegrants were filed in
Table 1 Commercially available superdisintegrants
Type of polymers Commercially available brand
Sodium starch glycolate Primogel, Explotab, Tablo,
Vivastar
Cross-linked sodium
carboxy methylcellulose
Ac-di-sol,Nymcel, Primellose,
vivasol, solutab
Soy polysaccharide Emcosoy
Crosslinked polyvinyl-
pyrrolidone
Polyplasdone, Kollidon CL
Gellan gum Kilcogel
Xanthan gum Grindsted, Xanthan sm
Ion exchange resins Indion 414, Tulsion 339, Amberlite
IRP 88
Table 2No. of patents filed for superdisintegrants during
1983-2006
Year No. of patents
1983-1988 1
1989-1993 4
1994-1997 8
1998-2000 10
2001-2004 22
2005-2006 7
BELE & DERLE: PATENTS PERTAINING TO SUPERDISINTEGRANTS IN TABLET MANUFACTURING


603
the Europian Union, followed by United States, world
patents, Australia, China, and minimum in Canada.
Table 3 gives the data for different super-
disintegrants used and number of patents. It is a
combined data obtained from NIC and USPTO
databases. From the table it can be seen that Amylose
is the most widely patented superdisintegrant. Very
little number of patents are found on formulations
containing conventional superdisintegrants like
Croscarmallose sodium, Crosspovidone, sodium
starch glycolate and few ion exchange resins. This
indicates that there is still a scope for exploring these
superdisintegrants in pharmaceutical tablet
formulations and patenting this research.

Activity Index
Activity index (AI) characterizes relative research
effort of a country to a given subject field. AI=100
indicates that the countrys research effort in the
given field corresponds precisely to the world
average. AI>100 indicates higher activity than world
average. AI< 100 indicates activity lower than the
average effort in the specified field. However, in the
present case it has been modified and has been used to
calculate AI of Europe vs rest of the world.
AI (of Europe)={(Europe output in a particular
year/total Europe output)/(world output in particular
year/total world output)} 100
AI for European Union as compared to rest of the a
world (AI=100) is given in Table 4.
European patents during the period 1983-2006
constitute about 38% of total patents filed over
superdisintegrant.
Analysis of data using AI for EU vs rest of the
world shows that AI for Europe decreased
considerably during 2001 2004. The value of AI
during 1989-1993 & 1994-1997 was 130 each, much
higher than the rest of the world. AI for 1998-2000
did not sustain and it decreased in periods 2001-2004
& 2005-2006.
The decrease in AI in Europe over the years 1997
to 2006 may be attributed to unavailability of the
newer superdisintegrants for pharmaceutical tablets.
But after the advent of the new era of
superdisintegrants in the market, there is no
significant rise in the AI which indicates that the
pharmaceutical formulations using these newer
superdisintegrants have not been studied and patented
extensively. The number of Indian patents filed were
found to be insignificant and indigenous excipients
manufacturing companies producing disintegrants
should focus their research in this area. There were no
patents filed worldwide on ion exchange resin
disintegrants which are widely being marketed for this
purpose and this research area remains unexplored.

Conclusion
The study indicates that number of patents filed on
superdisintegrants has increased significantly over the
years 2001-2004. Maximum number of patents were
filed in the year 2003 and in Europe. Maximum
number of patents were filed on cross-linked N-vinyl
2-pyrolidone (CLPVP) and sodium starch glycolate
combination.

References
1 Phadnis R, Hirwani R R, Patent analysis as a tool for research
planning: Case study of phytochemicals in tea, Journal of
Intellectual Property Rights, 10 (3) (2005) 221-231.
2 Indian Pharmacopoeia, volume II, (Government of India,
Ministry of Health and Family Welfare, New Delhi), 1996.
3 Lowenthal L, Disintegration of tablets, Journal of
Pharmaceutical Sciences, 61 (11) (1972) 1695-1711.
4 Banker G, Perck G, & Baley G (1980), Compressed tablets
in Pharmaceutical Dosage Forms: Tablets, Volume I , edited
by H Lieberman & L Lachman (Marcell Dekker, New York),
1980, 86.
5 Marshall K & Rudinic E M (1990). Tablet Dosage Forms, in
Modern Pharmaceutics edited by G S Banker & C T Rhodes
(Marcel Dekker Inc, NewYork), 1990, 355-426.
6 Rubinstin M Tablets in Pharmaceutics: the Science of
Dosage form Design, edited by M Aulton (Churchill
Livingston, New York), 1996, 309.
Table 3 Different superdisintegrants and no of patents
Name of superdisintegrant No. of patents
Amylose 14
Coprocessed starch 9
N-vinyl pyrilidone+ Na starch glycolate 15
Chitin 2
Coprocessed cellulose 4
Granulated starch+Veegum 1
Cellulose+ methyl acrylic acid 4
Compressed guar-gum 3
Table 4 Activity index for European Union
Period EU
patents
Total patents of
rest of the world
Activity
index(EU)
1983-1988 0 1 0
1989-1993 2 4 130
1994-1997 4 8 130
1998-2000 4 10 104
2001-2004 8 22 94.55
2005-2006 2 7 74.28
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604
7 European Pharmacopeia, Supplement 5.2 (2006), 3151.
European Directorate for the Quality of Medicines,
http://www.edqm.eu/medias/fischiers/E-Contents_List_5.2
.pdf (10 February 2007).
8 Cremer K, Orally disintegrating dosage forms provide life
cycle management opportunities, formulation and solid
dosage, Pharmaceutical Technology, 2003, 2228.
9 Amin A, Superdisintegrants: An economical alternative,
http//:www.pharma.com/magazine/current_issue/superdisinte
grants.htm (3 March 2007).
10 Tablet: Formulation of tablet- disintegrants. The
pharmaceutical encycloped, www.pharmapedia.com/Tablet:
Formulation_of tablets/Disintegrants (12 February 2007).
11 Fukami J, Ozawa A, Yoshihashi Y, Yonemochi E & Terada
K, Development of fast disintegrating compressed tablets
using amino acid as disintegration accelerator: Evaluation of
wetting and disintegration of the tablet on the basis of surface
free energy, Chemical & Pharmaceutical Bulletin, 53 (12)
(2005) 536-1539.
12 Anand V, Kandarapu R, and Garg S, Ion exchange resins:
Carring drug delivery farward, Drug Discovery Today, 6 (17)
(2001) 74.
13 Mahendale S V and Malshe V, The Eastern Pharmacist,
1991, 41.
14 Quadir A and Kolter K, A comparative study of current
superdisintegrants. Pharmaceutical Technology, 1 October
2006.
15 Camarco W, Ray D and Druffner A D Selecting a
superdisintegrant for orally disintegrating tablet
formulations, Pharmaceutical Technology, 1 October 2006.
16 Hughes L, Ion exchange resins: Unique solutions to formulation
problems, Pharmaceutical Technology, October 2004, 20.
17 Kolter K, Maschke A and Meyer-Boehm, K BASF
Akctiengesellschaft, Development Pharma Ingerdients C
http://www.apspharmsci.org/abstracts/AM_2006/AAPS2006
_0018 20. pdf.
18 Zhao N & Ausburger L, The influence of product brand-to
brand variability on superdisintegrant performance: A case
study with Croscarmellose sodium, Pharmaceutical
Development and Technology, 11 (2006) 179-185.
19 Carmella C, Ferrari F, Bonferroni M C and Ronchi M,
Disintegrants in solid dosage forms, Drug Development and
Industrial Pharmacy, 16 (17) (1990) 2561-2577.
20 Jerome B and Galenix J, Compositions containing
Hydroxypropylmethylcellulose and/or Ethylcellulose as
disintegrants and process for producing it, US Pat No US6,
531, 151, 11 March 2003.
21 Minhua F, Oral disintegrants of Nimodipine and their
preparation, Chinese Pat No, CN1582, 927, 20 August 2003.
22 Xudong Xu, Oral disintegrants of isosorbide mononitrate and
their preparation, Chinese Pat No. CN1582917,
23 February 2005.
23 Xudong Xu, Oral disintegrants of Breviscapine for
diseases of cardio-cerebral blood vessel and their
preparation, Chinese Pat No 1582955, 23 February 2005.
24 Makki-Morehead W, Buehler J and Landman B, Formulation
of fast dissolving effervescent capsules using
superdisintegrants, Europian Pat No EP1, 067, 936,
17 January 2001.
25 Du Pont Pharmaceuticals, Formulation of fast dissolving
effervescent capsules using superdisintegrants, Israeli Pat No
138, 078, 31 October 2001.