www.tecnologia.it

TECNOLOGIA MECCANICA

Process Solution = ʃ (Mechanical Technology, Process Knowledge, Experience, Prototypes )

T

History Founded in 1970 by Renato Locatelli.

Grown up devoting itself to the construction of the most advanced prototype systems for the local process industries.

Making the innovation as its main focus from the very beginning.

Today engaged in the Italian market for R&D in the most well known pharmaceutical/chemical/agrochemical labs.

Active worldwide in the micronization technology field with its own Fluid Jet Micronizers.

Highlights

Located in Northern Italy not far from Milan, It is a family owned and run company.

Tecnologia Meccanica offers process support services including rheology testing and micronization trials in order to provide the properly engineered design to meet your specific needs.

Equipment can be tailored to meet the customer’s requirements and specific product characteristics.

Full range of capacities including lab machines that start as low as 0.5 g/hour, up to production equipment with production capacities up to 1500 kg/hour.

Complete engineering design, product testing and

equipment manufacturing in its own facility

Micronization

With the term micronization it is indicated a method

of reduction of the dimensions that results in

powders under the 10 µm in size.

This technology is extremely important in different

industrial fields, in particular in the druggist field

where the reduction of the active principles (the so-

called API and HPAI) to such dimensions increases

exponentially the characteristics of Bioavailability,

of Bioequivalence, and the surface area available

of the product.

Tecnologia Meccanica fluid jet micronizers are able

to obtain an extremely narrow tight particle size

distribution curve of d100<5 µm (100% below 5

µm) and d99<3 µm (99% below 3 µm) or even less

depending on the nature of the product.

Our laboratory units can actually handle batches as small

as 0.2 grams and produce results of D99<3 micrometer

granulometry! With the milligram kit option even batches of

0.1 grams are possible.

Sympatec GmbHSystem-Partikel-Technik

HELOS Particle Size Analysis

WINDOX 5

HELOS (H1674) & RODOS, R2: 0.25/0.45...87.5µm 2005-01-24, 17:22:40

Fluticasone

x10 = 0,69 µm x50 = 1,24 µm x90 = 2,04 µm SMD = 1,11 µm VMD = 1,31 µm

x16 = 0,78 µm x84 = 1,83 µm x99 = 2,79 µm SV = 5,40 m²/cm³ Sm = 68404,38 cm²/g

0

10

20

30

40

50

60

70

80

90

100

Cum

ula

tiv

e d

istr

ibu

tio

n Q

3 / %

0.100.10 0.5 1 5 10 50 100

particle size / µm

cumulative distribution

x0/µm Q3/% x0/µm Q3/% x0/µm Q3/% x0/µm Q3/% 0,45 0,68 1,85 84,90 7,50 100,00 30,50 100,00

0,55 3,14 2,15 93,08 9,00 100,00 36,50 100,00

0,65 7,63 2,50 97,61 10,50 100,00 43,50 100,00

0,75 13,63 3,00 100,00 12,50 100,00 51,50 100,00

0,90 24,13 3,75 100,00 15,00 100,00 61,50 100,00

1,10 39,28 4,50 100,00 18,00 100,00 73,50 100,00

1,30 54,18 5,25 100,00 21,50 100,00 87,50 100,00

1,55 70,58 6,25 100,00 25,50 100,00

evaluation: WINDOX 5.1.2.0, HRLD stabil.9 product: Fluticasone

revalidation: density: 0,79 g/cm³, shape factor: 1,00

reference measurement: 01-24 17:22:17 disp. meth.: 3bar no vib

contamination: 0,00 % Copt= 0,41 %

trigger condition: tb500ms c.opt>0.2 always 20 .. user parameters:

time base: 500,00 ms Operatore: QLab

start: c.opt >= 0,2% ID: Fluticasone

valid: always Cliente: Tecnologia Meccanica

stop: 15,000s meas.time or 20,000s real time lotto: Trial2

The Process

Every technician involved in the micronization sector knows that the micronization process in the pharmaceutical industry is a critical, expensive and definitely complicated process. Even if a technician tries to find a solution by researching the enormous amount of literature available about size reduction, there is no single theory comparable to those existing for the other industrial processes, and consequently this requires that the problem be solved empirically and by utilizing years of experience.

Now that the modern global economy transfers the pharmaceutical processes from one side of the Earth to the other at warp speed, technicians need to implement both new and old process technology based on the existing technical literature without the comfort of years of experience. They find themselves mainly unprepared for the complexity of the micronization process, so the mix between the micronization process and globalization creates a difficult situation.

The Solution Tecnologia Meccanica has addressed these

troubles by developing a new family of Spiral

Fluid Jet Mills with enhanced characteristics

based on the following processing principles:

inexpensive and easy to operate

able to process products with high solvent

content (around 3000 ppm)

able to process sticky powders which do not

flow well

Our Jet Mills are based on a sound original

statistical matrix model implemented on

computer software which allows us to approach

the micronization process based on proven

methodology and in a comprehensive manner.

Briefly we can say that we have the technical

capability to make the micronization process an

easy process routine to validate/revalidate.

The Performance

The micronization process is always a function of

the product rheology.

Therefore once the fluid jet mill has reached its

performance limit with a given product rheology

and we need to go beyond this limit, we have a

problem to be solved.

Since we do not supply only machines but also

process oriented solutions, we are equipped with

the right mix of capabilities including:

Mechanical technology

Process knowledge

Experience

Prototypes design

Let’s see our Advantages in detail

Mechanical Technology

As a manufacturer of prototype systems, we still

maintain in-house all the necessary human

resources and manufacturing capabilities.

We have Engineering, Information technology,

Testing center, Non Destructive Testing

laboratory, and mechanical/carpentry/polishing

capability in our own Workshop.

5000 m² area, 2000 m² covered

EC Norms, TUV Inspected

Process Knowledge Developing new technologies by combining

the knowhow from different application fields

makes sense only with a basic knowledge of

the chemical manufacturing process.

We share an history of networking

knowledge with our customers which assists us

in designing process oriented machines.

Within our team we always have the right

technologist able to speak the same

language as our customer.

Therefore we can commit ourselves to

understanding the customer’s process

requirements.

Experience

All of you will agree with us that

technology without experience is

incomplete.

Our team is composed of mostly middle

aged people, with plenty of experience

and with all the necessary energy to

operate in a worldwide market.

We are prepared to commission and

finalize our machines to your process

requirements at your facility.

Prototypes

We are able to handle projects which do not

seem to be practicable and we address the

problems by sharing knowledge gained in

other fields.

In so doing, the capability to develop

working prototypes is a must and we

maintain a living testing center which in

reality is an effective prototype laboratory.

We enjoy the challenge and a result of our

experience in dealing with these often

difficult problems has generated fruitful

results, our micronization technology being

one of these.

Conclusion

We supply the best micronization technology

available on the market and we continue our

R&D work to anticipate our customer’s

requirements.

However, micronization technology has a limit

which can be overcome only with the right

function: ʃ (Mechanical Technology, Process

Knowledge, Experience, Prototypes )

CIP/WIP/SIP, process containment, machine

isolation, process validation, etc. are all

important matters, but please do not forget

that they come always after the process

solution.

Milestones & References

Milestones 1974, birth year of the first fluid jet mill for chemicals

1980, introduction of the octagonal milling chamber

1988, design of the non tangential Venturi entry for pharmaceuticals

1994, statistical matrix implementation on computer based software

2000, single V clamp execution on all the models

2003, birth year of the J-20 laboratory fluid jet mill

2005, modular system for J-20 / J-25 / J-30 and J-40 / J-50 / J-70

milling chambers

2006, introduction of the elliptical milling chamber

2008, J-100 / J-125 / J-150 in plant execution for medium small

productions

2009, high efficiency execution for sticky products and with high

solvent content

2010, glass lined process side parts

2011, fluid jet combo from r&d up to production capacity in one unit

2012, super vacuum technology for even easier micronization and

micro feeding technology

2013, continuous manufacturing for micronization processing

References BRAZIL

Cristalia Produtos Quimicos Farmaceuticos Ltda

EMS S/A

IIPF – Instituto Internacional de Pesquisas Farmaceuticas

Libbs Farmaceutica Ltda

CHINA Army Medical University

Asymchem Life Science Co. Ltd

Harbin University

Jiangsu Aosaikang Pharmaceutical

Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd.

Shandong Bio-Drug Study and Research Institute

Shanghai Chenpon Pharmaceutical Co. Ltd

Shanghai Fosum Omni Pharmaceutical Co. Ltd

Shenzhen Wanhe International Co. Ltd.

Yancheng Xinyi Pharm & Chem Co. Ltd.

CROATIA Pliva

GERMANY Wolff Cellulosics

HUNGARY Xellia Pharmaceuticals Ltd

INDIA Aarti Healthcare Ltd

Apex Laboratories private limited

Aventis Pharma Ltd

Panacea Biotech Ltd

Shasun Chemicals and Drugs Ltd

Sparc Ltd

Sun Pharmaceutical Industries Ltd

INDONESIA Bernofarm Pt.

IRAN Aryan Beris Co. Ltd

Azad University of Tehran

B.P.O. Research Center

JORDAN Polyplain Industries

ITALY 3V Sigma Spa

A.C.R.A.F. Spa – Angelini

Arsonsisi Spa

Barilla Spa

Chemessentia Srl

Ciriaf – Università di Perugia

Dipharma Francis Spa

Directa Plus Spa

I.N.F.N.

Henkel Spa

Lundbeck pharmaceuticals Spa

Microchem Srl

Pemco Emails Srl

Phytoremedial

Polimeri Europa Spa

Pulverit Spa

R&D Innovaction Srl

Società Chimica Larderello Spa

Solmag Spa

Soremartec Italia Srl

Università di Salerno – Dip. Scienze Farmaceutiche

Vamp Tech Spa

MEXICO Helm de Mexico

SINGAPORE 3M Innovation Pte Ltd

SYRIA Asia Pharmaceutical Industries

SWITZERLAND Flarer Sa

Helsinn Chemicals Sa

Jetpharma Sa

Micro-Sphere Sa

Nestlè

Nestec Sa

Solmer Sa

TURKEY Kontrol Kymia AS

UK Genesis Biosciences

Resolution Chemicals Ltd

U.S.A. 3V Inc. Georgetown

Technic Inc. Engineered Powders Division

Case of Study

Inhalers

Inhalers

Our customer is active in the market of

pharmaceutical lactose, of dry powder inhalers

and development of drug delivery systems.

The specific product was Fluticasone Propionate

CAS registry number [80474-14-2] and according

to international Pharmacopeia (FDA BA-BE Draft

Guidance 2003) it needs to be micronized in the

range of 1 to 5 micrometer under identical

parameters for suspension formulations.

According to our customer’s past experience:

Jet Milling was a technology with limitations on producing the correct particle size distribution for inhaled APIs.

It produced material with a significant amorphous content, which in turn can influence the stability of the finished formulation.

The micronization process can lead to reproducibility problems and creates the potential for metal contamination from the milling machine.

Inhalers

Tecnologia Meccanica was able to give a

working process solution:

Our micronization technology with high

pressure at reduced energy consumption

was able right from the beginning to process

the product and avoid the creation of

amorphous content.

Our rheology analysis made clear that the

product flow ability had not been previously

considered during process development.

Consequently reproducibility and incorrect PSD

were addressed by supplying our fluid jet mill with

the correct feeding technology.

No metal contamination was found when using our

process.

Partners

Tecnologia Meccanica works worldwide in cooperation with:

for process gas technology and process gas supply

Thank you

We thank you for your time & attention, We look forward to meet you in our workshop soon or at the next coming CPhI.