Download Pulverization to 100 nanometers in only 2 minutes!?

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Pulverization to 100 nanometers
in only 2 minutes!?
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Nano pulverization at low temperature.
Ultralow volume (100 mg) pulverization
is completed in 2 minutes at the shortest.
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We present NP-100 with confidence to fulfill your needs in the field of
pulverization. THINKY MIXER plays an active role in various areas nowadays,
enabling us to interact with people in a wide range of fields.
The development for NP-100 has started by a researcher who has been a user
of THINKY MIXER, suggesting the possibility of pulverizing nano materials.
The development from a brand new viewpoint brought constant challenges
and difficulties. With many researchers assistance and cooperation, we could
overcome numerous hardships and invented the unique and innovative
pulverizer, NP-100.
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NP-100 planetary centrifugal nano pulverizer has an optimal rotationrevolution ratio to maximize the collision energy of the pulverizing medium.
It generates strong centrifugal force during rotation and revolution, and the
pulverizing medium accelerates to crush the materials in the container.
The significant improvement in pulverization efficiency allows ultralow
volume (100 mg), fine crushing (100 nm), and short-time (2 minutes)
pulverization which used to be regarded as impossible. Moreover, the
mounted cooling mechanism can decrease the temperate inside the
chamber to -20 $C, reducing the risk of contamination and keeping the
crystal structure of compounds with low melting point during nano
pulverization.
Excellent operability provides simple operation; a batch system without
troublesome cleaning and a mesh filter to easily collect the medium after
pulverization. Since NP-100 pulverizes both inorganic and organic materials
and crushes a minimum amount of sample as needed, it is utilized as an
essential tool for researches with high-cost/high-tech materials. NP-100 s
NP-100 Nano Pulverizer
areas of activities are expanding not only in medical but in various fields.
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Principle of THINKY Planetary Centrifugal Pulverization
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NP-100 is the revolutionary pulverizer that applies the same planetary centrifugal system as THINKY MIXER.
The planetary centrifugal system consists of 2 axes where the container rotates counterclockwise while revolving clockwise at
a certain radius around an axis. The pulverizing medium, zirconia balls that have excellent abrasion resistance are placed in the
container, which then rotates and revolves at high speed to apply centrifugal force to the medium. The pulverizing medium
with centrifugal force crushes against the material and the collision energy makes the material finer.
Revolution
Rotation
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Advantages of NP-100 <Exceptional superiority>
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NP-100
Pulverized / Deagglomerated Samples
■ Medical and pharmaceutical materials
●Phenytoin (Low solubility compounds)
Before
Parameter
2000 rpm 2 min
Parameter
2000 rpm 3 min
Compound
Phenytoin
Compound
Indomethacin
Weight
100 mg
Weight
100 mg
Concentration
10 mg/ml
Concentration
10 mg/ml
Before
Zirconia ball
（φ0.1 mm）
Grinding tool
■Particle size distribution
After (SEM image x30 K)
●Indomethacin (Low solubility compounds)
D50
Before
5.774
10.58
18.639
After
0.069
0.125
0.231
■Particle size distribution
D90
D10
Before
After
After (SEM image x30 K)
Particle Size Distribution
14
12
10
8
6
4
2
0
0.01
Zirconia ball
（φ0.1 mm）
Grinding tool
（μｍ）
D10
（μｍ）
D50
D90
3.89
12.894
37.092
0.069
0.126
0.237
Particle Size Distribution
12
Volume (%)
10
Volume (%)
0.1
Before
Nano Pulverizer
1
After
10
Particle Size ( m)
100
8
6
4
2
0
0.01
1000 3000
0.1
Before
1
After
10
Particle Size ( m)
100
600
NP-100
Nano Particle Formation of Low Melting Point Compounds
For nano pulverization of low melting point compound, control of both excessive pulverization energy and heat generation
is essential in order to reduce amorphous particles. NP-100 has been proven to conduct nano pulverization of low melting
point compounds by decreasing the rotation speed, using the cooling mechanism to achieve a low temperature environment
at -20 °
C to cool the zirconia container effectively, and selecting the best solvent for the compound.
■ Crystallinity evaluation method after pulverization
Crystallinity:
Powder X-ray diffraction
Melting point
115 ℃
Verification sample 〈Compound〉100 mg
〈Medium〉
（3）
Probucol
Melting point
125 ℃
〈Temperature before
and after pulverization〉
6.3 ℃ to 20.3 ℃
D50：
0.108 ± 0.004 μm
D90：
0.186 ± 0.004 μm
(N=3)
Particle size（μm）
: Original bulk
: Pulverized bulk
２ θ（°
）
: Original bulk
: Pulverized bulk
Temperature
（℃）
Intensity（cps）
２ θ（°
）
Particle size（μm）
: Original bulk
: Pulverized bulk
: Original bulk
: Pulverized bulk
: Original bulk
: Pulverized bulk
Temperature
（℃）
Reference paper：Nano-pulverization of poorly water soluble compounds with low melting points by a rotation/revolution pulverizer K.Yuminoki, M.Takeda, K.Kitamura, S.Numata, K.Kimura,
T.Takatsuka, N.Hashimoto Journal of pharmaceutical sciences 103:3772-3781, 2014
7
φ0.1 mm, 2.5 g
0.3 ％ MC solution：
0.5 ml (SDS added)→ 9.5 ml
D50：
0.131 ± 0.002 μm
D90：
0.312 ± 0.024 μm
(N=3)
: Original bulk
: Pulverized bulk
Temperature
（℃）
DTA（uV）
Flurbiprofen
φ0.1 mm, 2.5 g
0.3 ％ MC solution：
0.5 ml → 9.5 ml
〈Temperature before
and after pulverization〉
0 ℃ to 15.5 ℃
: Original bulk
: Pulverized bulk
: Original bulk
: Pulverized bulk
（TG / DTA）
２ θ（°
）
Particle size（μm）
Intensity（cps）
Verification sample 〈Compound〉100 mg
〈Medium〉
（2）
D50：0.129
± 0.006 μm
D90：0.508
± 0.340 μm
(N=3)
Intensity（cps）
80 ℃
Volume（％）
Melting point
Volume（％）
Fenofibrate
φ0.1 mm, 2.5 g
0.3 ％ MC solution：
0.5 ml → 9.5 ml
〈Temperature before
and after pulverization〉
0 ℃ to 9.3 ℃
: Original bulk
: Pulverized bulk
DTA（uV）
（PXRD）
Representative diameters: D50 and D90 ( m)
Verification sample 〈Compound〉100 mg
〈Medium〉
（1）
Crystallinity: Thermogravimetric and
differential thermal analyzer
DTA（uV）
Particle size distribution:
Laser diffraction
Volume（％）
低
化合 物のナ
粒子Melting
化
Pulverized / Deagglomerated
Samples
/ Nano Particle
ofノLow
Point Compounds
Pulverized
/ Deagglomerated
samples
/ 融 点Formation
Nano Pulverizer
Operation
Nano Pulverizer
NP-100
Operation
■Precool before pulverization
Dummy weight
Temperature
Indicator
UP／DOWN
● Cooling time in the chamber
Atmosphere temperature（℃）
Mode switch
and SET UP
CHILLER
ON／OFF
Time (minutes)
Approx. time to cool to -20 °C
Cup holder
■ Temperature indication : ≈30 minutes
(Temperature of the chamber interior atmosphere)
■ Cup holder : ≈60 minutes
Counter balance adjustment dial
■ Basic operation (Pulverization)
45°
Solvent
Wet
pulverization
Add solvent
Materials
Pulverization
Mixing
400 rpm, 1 min
MILL/MIX Mode
Zirconia ball
MILL/MIX Mode
■ Basic operation (Separation of media)
Revolution
Mesh filter
Separating Media
2000 rpm, 1 min
Dispersion
400 rpm, 1 min
CLEAN MEDIA Mode
MILL/MIX Mode
8
Users’ Voice / Column
Nano Pulverizer
NP-100
Users’ Voice / Column
■Users’ voice
NP-100 nano pulverizer is essential for the study of next-generation batteries
important along with scaling up is enhancement
The conventional porous carbon electrodes
of battery performance. I study exponential
mentioned before were thick but had a problem
improvement in flow battery performance by
of long travel distance of ions, which limited
the efficient supply of electrolytes to porous
performance improvement. However, thinner
carbon electrodes so that the phase interfaces
electrodes had smaller ion reaction areas. Then,
formed by the electrodes and the electrolyte
a compact carbon layer is formed on the surfaces
can be used to the limit.
of the thin electrodes to increase the surface
Trigger to adopt NP-100 and
the area of the use
area and ensure sufficient reaction area,
Shohji Tsushima
I had used THINKY MIXER before for preparation
particles. When the carbon is placed on the
Professor, Doctor (Engineering)
Department of Mechanical Engineering,
Graduate School of Engineering,
Osaka University
of electrode material slurries of polymer electrolyte
electrodes, the carbon and solvent are prepared
fuel cells. Before that, a mortar was used for
like ink and applied by an inkjet printer with small
manual mixing. Someone introduced THINKY
nozzles. Therefore, the carbon particle sizes need
MIXER as the de facto standard and I adopted it.
to be kept fine, and NP-100 fully works with it.
The variation in the finish among operators
Research overview
In addition, the capability of ultralow-volume
was eliminated, and the efficiency of experiments
processing, the cooling function, and excellent
was improved remarkably. Then, I initiated the
The current major objects of study are flow
reproducibility also match the needs. I continue
study of flow cells as a member of Phase Interfaces
batteries (redox flow batteries) and polymer
to make full use of this equipment to contribute
for Highly Efficient Energy Utilization Project
electrolyte fuel cells. Flow batteries can easily
to the research and development of future energy
of JST Strategic Basic Research Programs Sakigake,
be scaled up, and they are expected to become
devices.
and NP-100 was adopted for deagglomerating
a large-scale power storage device. What is
and pulverizing the electrode material carbon.
achieving both thinness and performance.
NP-100 is used to deagglomerate the carbon
■Column
NP-100 joint developer’s untold story of the development
the suspended drug to animals, and it is most
important to create a uniform suspension
because uneven suspensions do not administer
constant doses of the drug, causing variations in
the data. Compared with conventional stirrer
mixing, THINKY MIXER is easy and can prepare
a uniform suspension in a short time. I proposed
that THINKY MIXER should be used for safety
studies in the laboratories of Pfizer in each country,
Naofumi Hashimoto
Professor, Doctor (Pharmacy)
Department of Pharmaceutical Sciences,
Faculty of Pharmaceutical Sciences,
Setsunan University
Development of NP-100
I started using THINKY MIXER more than ten years
ago to prepare suspensions for safety studies at
the Research Laboratories of Pfizer Inc., where I
worked at the time. Safety studies are tests to
examine adverse effects and toxicity by feeding
9
and it was accepted. On the other hand, my
subordinate conducted an experiment to obtain
finer particles by stirring the drug suspension,
and I thought the beads put in THINKY MIXER
could crush the drug finer and quicker. I tried it
to achieve pulverization of the drug from several
hundred microns to several microns. The operation
duration, which used to be a whole day, was
shortened to several minutes. After that, the
Research Laboratories closed, and I moved to
the university to continue research, as well as
promote the development of nano pulverizers
together with THINKY.
Major advantages to pulverize
the drug into nano particles
Nano particles of the drug have exponentially
increased the total surface area of the powder,
leading to higher dissolution rates and better
absorption from the gastrointestinal tract after
oral administration. Forming nano particles was
a very effective method for drugs with high
pharmacological activity and difficult dissolution
in water, which puzzled researchers at that time.
In addition to the improvement in absorbability
of oral administration, pulverization to 200
nanometers or less enabled application to various
routes, including ocular instillation, transdermal,
intravenous and intramuscular administration.
While a larger dose may cause adverse effects,
such as variations in absorbability and side
effects, use of nano particles eliminates the need
for an excess administration of drugs and achieves
medicinal action with a smaller dose than
conventional doses. Nano particle drug formulation
leads to the development of safer medicines and
may increase dramatically in the future. I am very
glad to know that this equipment is now used in
different fields.
Latest Optional Tools / Our Support System
Nano Pulverizer
NP-100
Latest Optional Tools / Our Support System
■ Latest optional tools
Zirconia containers to pulverize
minimum of 10 ml material
● Simultaneous process of two samples in 10 ml zirconia containers
The two data overlaps
each other.
10 ml zirconia container lid
10 ml zirconia containers x2
µ
10 ml zirconia container
adapter
10 ml zirconia container set
●Maximum
liquid feed amount: 10 ml
amount of pulverization: 10 to 100 mg
●Recommended recipe available (pulverizing phenytoin)
●Recommended
Comparison with the
standard container
(80 ml container)
* The particle sizes of the two samples are uniform.
●Particle size difference when pulverizing 100 mg or less material in
10 ml zirconia container (red) and 80 ml standard container (green)
µ
* Compared with the standard container, the 10 ml zirconia container tends to have
more uniform pulverized particle sizes. The reason is that the small diameter of the
10 ml container increases frequencies of collisions between the balls and the
material to contribute to pulverization efficiency.
●Increased frequency of collision between balls and
material to improve pulverization efficiency
●Simultaneous process of two samples to increase
efficiency
●Tendency of more uniform particle sizes after
pulverizing 100 mg or less
●Less heat generation during pulverization
●Reduced material loss due to adhesion of the container
■ Our Support System
Two secure support systems
After-sales support
If you have any problems with a product, please contact us.
Application engineering
THINKY s professional application team supports parameter settings
Please contact THINKY CORPORATION
Email: [email protected]
THINKY
http://www.thinkymixer.net/
for customers. Before demonstration of pulverization, implementation
of preliminary examination enables smooth presentation of the
demonstration. Contact THINKY CORPORATION listed on the back cover.
THINKY continues to assist customers
with our full support system.
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Sales agent
“NIPPON MONOZUKURI”INNOVATOR
H e a d q u a r t e r s : 2-16-2 Sotokanda, Chiyoda-ku, Tokyo 101-0021
Phone : +81-3-5207-2713 Fax : +81-3-5289-3281
THINKY USA Inc. : 23151 Verdugo Drive, Suite 107 Laguna Hills, CA92653, USA
THINKY CHINA: East building, HaiAn Kafunuo Mansion, Shennan road,
Qianhai road, Nanshan district, Shenzhen
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