Traditional Medicine meets modern excipients

We shape your traditional formulations

Dr. Kathrin Meyer-Boehm and Kevin Wang (BASF China),

two enablers in excipients

Pharma Ingredients & Services. Welcome to more opportunities.

Custom Synthesis | Excipients | Active Ingredients
Exceptional excipients for
traditional formulations

“I grew up with Traditional Medi-

cine, and I want to make sure it con-
tinues to flourish in the 21st centu-
ry and beyond. But to achieve this,
we must embrace the potential of
innovative and modern excipients –
without sacrificing the values of
Traditional Medicine…”

…explains Kevin Wang, a BASF enabler. He knows that to ensure

the success of Traditional Medicine products in today’s market,
manufacturers must enhance the unique benefits of their formu­
lations with cutting-edge excipients. Together with his colleagues
at BASF Asia Pacific, Mr. Wang explores how exceptional products
such as high-performance solubilizers, innovative taste-masking
and protective coatings, and effective disintegrants can revolu-
tionize traditional products and enhance patient compliance –
opening up a whole new world of opportunities.

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Traditional Medicine: founded on tradition –
but with an eye to the future

With a rich history spanning thousands of years, Traditional Chinese Medicine

has had a major influence on medical practice around the world – from
Kampo in Japan or Jamu in Indonesia to traditional Korean medicine. Recent
years have seen renewed interest in traditional formulations from all four
corners of the globe, making herbal remedies more popular than ever before.

But if these products are to secure and expand their market

­position, they must respond to today’s challenges – as Professor
Ping Qineng, Dean Emeritus of the School of Pharmacy at China
Pharmaceutical University and Former Vice Director of Pharma-
ceutics Discipline for the China Pharma­ceutical Association, ex-
plains:

“Traditional formulations need special care. The unique proper-

ties of traditional herbals are one of the biggest challenges faced
by formulators: it is essential to use modern technologies and
­excipients in order to meet patients’ needs.”

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Traditional Medicine:
overcoming the challenges

In order to perform to their full potential, Traditional Medicine products must

surmount a number of obstacles. Because traditional formulations demand
high concentrations of natural ingredients, the excipients used must be
effective in small doses. Poor solubility and long disintegration times can
impede the delivery speed of active ingredients, while high stickiness and
viscosity can create problems when processing herbal extracts. Moreover,
effective taste masking and color coating are a must in order to ensure
patient compliance. But whatever the challenge, BASF has a solution: read
on to find out more.

4
How innovative excipients can revolutionize
Traditional Medicine

Traditional herbals: challenging properties Traditional Medicine: formulation challenges

¢ Poorly soluble ¢ High dosage of natural ingredients

¢ Moisture sensitive ¢ High viscosity of herbal extracts
¢ Unpleasant taste or odor ¢ Extreme stickiness of herbal extracts
¢ Dark, uneven coloring ¢ Poor disintegration of formulations
¢ Heat sensitive ¢ Moisture sensitivity of formulations
¢ pH sensitive ¢ Unpleasant taste or odor of formulations

High-performance excipients for Traditional Medicine

BASF excipients turn traditional formulations into

modern solid oral dosage forms (SODFs), offering:

¢ Tailor-made solutions for reformulating traditional products

¢ Exceptionally easy-to-process excipients
¢ More efficient production and lower costs
¢ Improved biocompatibility

5
The challenges faced by Traditional Medicine –
and BASF’s solutions

A Solutions for rapid Disintegration time of Traditional Medicine tablets featuring

­various disintegrants (concentration of disintegrant: 15 %)

­disintegration
50

Disintegration time [min]

40
When it comes to Traditional Medicine tablets, the large volume of
herbals required can limit the amount of excipients that can be 30
added. Which means the disintegrant used must be highly effec­
20
tive if the desired disintegration time is to be achieved. Where
standard disintegrants often fall short, BASF’s Kollidon® CL de­ 10
livers real results. In the test depicted in this graphic, Kollidon® CL
0
produced the highest disintegration speed (18 minutes) – 50 per­
Kollidon® CL CMC-Na CMS-Na
cent faster than croscarmellose ­s odium (CMC-Na: 27 minutes)
and almost three times faster than sodium starch glycolate
­(CMS-Na: 50 minutes). Comparing the efficiency of disintegrants in
Traditional Medicine tablets

B Solutions for reliable

Impact of various coating excipients on disintegration of green
tea tablets (coating level 4.5mg/cm², 10 days, stressed conditions)

taste masking
Disintegration time [min]

60
50
Delivering effective protection from bitter tastes or unpleasant 40
odors can often present a challenge when formulating Tradition­ 30
al Medicine tablets. Kollicoat® Smartseal 30 D offers a solution, 20
ensuring effective taste masking without compromising on the 10
release times of active ingredients once swallowed. In the ex­ 0
ample given here, when applied to green tea tablets, Kollicoat® 0.1 M HCI pH 7.0 PBS
 Reference 1: polyvinylalcohol system
Smartseal 30 D provided the greatest protection in the mouth
 Reference 2: HPMC system
(pH 7) yet rapid disintegration in the stomach (pH 1) – even after  Reference 3: cationic copolymer based on methacrylates
10 days stored under stressed conditions.  Kollicoat® Smartseal 30 D

Disintegration of green tea tablets in HCI and phosphate

­buffer system pH 7

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C
Solutions for robust
protection
When exposed to moisture, tablet cores can swell and coatings
can crack. The outstanding film flexibility offered by Kollicoat®
Protect delivers exceptional moisture protection and prevents
tablet damage. Instant-release reference Kollicoat® Protect

After 14 days’ storage at 40°C/75 % humidity

The pictures shown here compare a HPMC instant-release
coating with Kollicoat® Protect: the HPMC coating has buckled
under the pressure of 14 days’ storage, whereas Kollicoat ®
­Protect remains perfectly intact.

D Solutions for biocompa- Test material Histamine release level [ ug / l ]

tible reformulation Marketed product

containing polysorbate 80
15-16

Egg white as
Adverse reactions to Traditional Chinese Medicine injections 15-16
positive reference
have prompted the Chinese State Food and Drug Administration
(SFDA) to call for a re-evaluation of formulations and production Injection formulation
11-12
containing Kolliphor® HS 15
processes as a prerequisite for market approval. BASF can help
you re-formulate your traditional injections, using solubilizers Saline 11-12
such as Kolliphor® HS 15. “When used in asarone injections,
the solubilization capacity of Kolliphor® HS 15 is comparable
Source: Prof. Gong Tao, West China School of Pharmacy,
with polysorbate 80. Yet the histamine release profile of Kolliphor® Sichuan University, Chengdu, China
HS 15 is similar to saline, leading to the conclusion that
­Kolliphor® HS 15 is more biocompatible,” states Prof. Gong
Tao, West China School of Pharmacy at Sichuan University.

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Whatever the challenge, BASF has the perfect solution
for Traditional Medicine formulations

Disintegration Color coatings

Achieve your target disintegration times – Create your own colors to cover dark herbs –
with Kollidon® CL grades. with Kollicoat® IR Coating Systems.

Kollidon® CL is the industry’s widest portfolio of Distinctive coloring, robust, and rapidly soluble:
superdisintegrants and disintegration enhancers. Kollicoat® IR Coating Systems allow you to cre-
These highly functional cross-linked PVP poly- ate tablet coatings in countless shades, using
mers ensure that active ingredients are released only seven base colors. The high-quality, flexible
from any solid dosage form at exceptionally high and efficient coatings are based on Kollicoat®
speed. IR, a polyvinyl alcohol-polyethylene glycol graft
copolymer.

Taste masking Solubilization

Cover the bitter taste of herbal formulations – Overcome the poor solubility of Traditional
with Kollicoat® Smartseal 30 D. Medicine – with Soluplus® and ­Kolliwax®,
Kolliphor®, Kollisolv®, and ­Kollicream®
Kollicoat® Smartseal 30 D effectively protects grades.
bitter and moisture-sensitive ingredients:
it ­remains stable in saliva yet ensures rapid Our extensive portfolio of solubilizers and
­release of active ingredients in the acidic en­ ­cosolvents is designed for all common dosage
vironment of the stomach. forms, including solids, liquids and semi-solids.
It delivers effective solutions for formulating
­Traditional Medicine injections, creams, tablets,
extrudates and more.

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Granulation Clear and flexible coatings

Granulate herbal powders before direct tablet com- Achieve a clear and flexible coating without requiring
pression – with binders such as Kollidon® grades, an additional plasticizer – with Kollicoat® IR and
Kollicoat® IR and Kollicoat® IR Coating Systems. Kollicoat® Protect.

Kollidon® grades can be used as a dry binder for direct Kollicoat® IR and Kollicoat® Protect are water-soluble film-
compression tableting and as a soluble binder for granu­ forming agents ideal for manufacturing instant-release
lation. Their exceptional binding properties make them an coatings for solid dosage forms. Robust yet flexible, they
­attractive and cost-effective alternative to natural binders. can be sprayed quickly and easily thanks to their high pig-
ment-binding capacity.

Moisture protection Sustained release

Protect sensitive natural ingredients from moisture Create custom sustained-release profiles for your
and ensure performance in solid oral dosage forms – herbal formulations – with Kollicoat® SR 30 D, and
with Kollicoat® Protect and Kollicoat® Smartseal 30 D. combinations of Kollicoat® SR 30 D and Kollicoat® IR.

Kollicoat® Protect is a highly flexible, easy-to-handle water- No matter what the dosage form, Kollicoat® SR 30 D enables
soluble film former that requires no plasticizer. When used pH-independent release of active ingredients, with precisely
with pigments, it acts as an effective moisture barrier – the delay required. Combining the water-insoluble Kollicoat®
providing robust, reliable protection for active ingredients. SR 30 D with the water-soluble polymer Kollicoat® IR gives
Kollicoat® Smartseal 30 D, a film former that is soluble you even greater flexibility when it comes to creating cus-
in gastric fluid, is a further option for creating a highly tom dissolution profiles.
­impermeable water barrier.

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Pharma Ingredients & Services. Welcome to more opportunities.
Custom Synthesis |
Excipients | Active Ingredients

BASF would like to Prof. Ping Qineng

Taking tradition into the future. Tap into the benefits of BASF thank our partners School of Pharmacy, China
­Pharmaceutical ­University
excipients for your traditional formulations: for their valuable
contributions:
Prof. Du Shouying
¢ Tailor-made solutions for reformulating traditional products School of Chinese Materia
­Medica, Beijing University of
¢ Exceptionally easy-to-process excipients ­Chinese Medicine

¢ More efficient production and lower costs Prof. Gong Tao

West China School of Pharmacy,
¢ Improved biocompatibility Sichuan University

Prof. Di Liuqing
School of Pharmacy, Nanjing
­University of Chinese Medicine

To find out more about how BASF can enhance your Traditional
Medicine products, contact our formulation experts:

China India Indonesia

Kevin Wang Dr. Vaishali Tawde Sigit Purwadi
Phone: + 86 1860 1362 885 Phone: +91 9833 1774 39 Phone: +62 811 851 415
[email protected] [email protected] [email protected]

03_121201e-00
TCM Application Center Japan Korea
Dr. Kathrin Meyer-Boehm Junichiro Kishi Warren Kim
Phone: +86 1370 1747 590 Phone: +81 3 3796 9225 Phone: +82 10 9113 6619 www.pharma-ingredients.basf.com
[email protected] [email protected] [email protected] [email protected]

Disclaimer
The data contained in this publication are based on our current knowledge and experience. In view of the many factors
that may affect processing and application of our product, these data do not relieve processors from carrying out their own
investigations and tests; neither do these data imply any guarantee of certain properties, nor the suitability of the product
for a specific purpose. Any descriptions, drawings, photographs, data, proportions, weights etc. given herein may change
without prior information and do not constitute the agreed contractual quality of the product. It is the responsibility of the
recipient of our products to ensure that any proprietary rights and existing laws and legislation are observed. (10/ 2012)
® = registered trademark of BASF SE