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Dec 6, 2012 (4 years and 11 months ago)

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CENTER OF KNOWLEDGE AND
TECHNOLOGIES TRANSFER


Elena Guseva
1


Natalia Menshutina
1
, Hans Leuenberger
2

1
D.I. Mendeleev University of Chemical
Technology of Russia

2
University of Basel, Switzerland


In the beginning…

Russian
-
Swiss scienc
e

and education center
for transfer of
biopharmaceutical technologies

has been established on the bas
is

of
MUCTR as the result of team
-
work

between
the
Institute

of
Pharmaceutical Technology, University
of

Basel and MUCTR.

The Russian
-
Swiss scienc
e

and education center
has

the

official
status of the structural unit
o
f MUCTR.

The Center is a new bas
is

to enhance the Russian
-
Swiss
relationship
in

education, science and technology transfer for mutual
benefit.


The center was founded under support of:


Russian Ministry of Education and Science


State Secretariat for Education and Research SER


Swiss Embassy in Moscow

MAIN AIMS AND TASKS


co
-
ordination

of

students

education

on

special

master

courses

using

the

Centre’s

facilities,

equipment

and

materials

in

accordance

with

European

standards

and

technical

requirements
;


organisation

of

specialised

laboratories

within

the

university

for

the

purpose

of

conducting

scientific

studies

profile
;


advanced

training

of

specialists

from

appropriately

profiled

enterprises
;


publication

of

relevant

successes

and

popularization

of

intellectual

achievements

of

Russian

and

Swiss

research

organization

to

improve

commercial

appeal

to

the

international

market
.


EDUCATIONAL ACTIVITY


graduate

unique

specialists


promote

knowledge

to

practice


cultivate

understanding

of

technology

“We grow people for you”

INDUSTRY

UNIVERSITIES

Technology + Equipment


Competent specialists

(
Masters, PhDs)

TRAINING OF SPECIALISTS


Improvement of skills

and
training courses

were developed for Russian pharmaceutical
specialists:





«
Technologies and equipment for




pharmaceutical industry
»




Granulation
,
Drying
,
Coating



(
together with

Glatt, Huettlin, BASF, Evonik
)




Quality management





PAT







WEB
-
PORTAL
«PHARMACEUTICS

ONLINE»

http://www.muctr.edu.ru/~cache/claroline


Availability


Quality


Usability


A

lot

of

classified

information,

useful

for

education

of

specialists

in

pharmaceutics

technology

area
:



Videos

(with

audio

explanations)



High
-
quality

photos



2
D

and

3
D

animations,


explaining

physical

and

chemical

processes,

processes

taking


place

inside

apparatus



Schemes

of

general

types

of

apparatus



Textual

information

with

binding

hyperlinks



Technical

descriptions

of

all

the

processes,

useful

in

pharmaceutics

technology

COURSE MATERIALS
.
LECTURES




Dosage dispersed forms
(671
slides
)




Solid drugs forms

(
~
400
slides
)




Liquid sterile drug

forms
(
~
250

slides
)




Equipment and Technologies of


Pharmaceutical Industry
(
~700 slides
,


18
lectures
)

01.04.2003
317
5.7 Rheogramm plastischer
Systeme
D

D

Fliessgrenze
Fliessgrenze
Bingham
Körper
Casson
Körper
(wird immer flüssiger)
01.04.2003
399
7.7 Franz Diffusionszellsystem
01.04.2003
336
6.2 Wasserabgabe über die
Haut
OUR BOOKS


«
Nanoparticles and nanostructured materials for
pharmaceutics
»


Menshutina N.V.


«
Information systems and databases for pharmaceutics
»



Menshutina

N.V
.,
Mesheryakova

T
.
V
.,
Goncharova

S
.
V
.,
Mishina

Y
.
V
.,
Leuenberger

H
.


M
.,
MUCTR 2002



«E
-
learning on chemical engineering and pharmaceutical
specialities»




Menshutina N., Mishina Ju., Guseva E., Leuenberger H., Chelnokov
V.


М., publishing house of scientific literature, Kaluga

2007


Visits
,
Abroad

Studying
,
Lectures

LAST 2 YEARS:



Students

-

8

Ph.D. Students



1
4

Lecturers



18

Abroad studying



2


EXCHANGE OF KNOWLEDGE

EQUIPMENT


HUTTLIN M
ycrolab

/
HUTTLIN

GmbH/


Mini
-
Glatt


/
GLATT

International GmbH/


Spray drying equipment

/
NIRO
/


Equipment for production micro
-

and nanoparticles
by dispersion
/
Own development
/



AMETEK
Proline Process Mass Spectrometer


Reverse osmosis equipment

R
02
-
50/
CP
-
HR



Oil
-
Free compressor

Atlas
-
Copco



Compressor

F
.
F
.




Vacuum compressor



Bioreactor



SKAN

Isolator equipment


Sonotec
Ultra
-
sonic nozzle

RESEARCH AND CONSULTING


Pharmaceutics


Freeze, Spray, Supercritical drying


Dispersion


Coating


Granulation


Encapsulation


Biotechnology


stress of microorganism


protein production


Nanotechnology


drug delivery

Information technology


PAT, LIMS


Software development

Development of new technologies

and Scaling
-
up:


ENCAPSULATION

Encapsulation by coating
in
fluidized layer under super
critical conditions

Protein encapsulation to
biodegradable
microspheres using freeze
drying technologies

Mannitol

Dextran

Spraying

Freezing

Sublimation of

fluidized


bed particles

Atmospheric freeze
-
drying
with

active hydrodynamics


… is alternative process to
classical vacuum freeze
-
drying


The process has two stages:



the initial freezing at spraying of the solution



the sublimation of frozen particles at their fluidization


The

initial

freezing

is

done

in

a

freezing

cabinet,

which

is

equipped

with

an

ultrasonic

nozzle

that

is

capable

of

producing

particles

of

150

mm
.

The

freezing

temperature

inside

the

cabinet

was

held

at


60

C
.

The

15
%

aqueous

solution

of

mannitol

is

sprayed

top
-
down

against

a

cold

air

stream
.


At

sublimation

drying

stage

of

the

process

the

frozen

particles

are

held

by

fluidization,

and

this

was

performed

in

the

modified

Glatt

apparatus
.

The

process

was

carried

out

at

a

drying

temperature

of

about

-
20
ºC
.

The

average

time

of

the

process

was

about

3

hours
.

The main stages and description

of the process


intensive heat and mass transfer, high moisture removal
rate due to active hydrodynamic regime


reduced time of the process


energy effectiveness in comparison with classical freeze
drying under vacuum


better control of the residual moisture content and
temperature, important for pharmaceutical products


product size and shape design for manufacturing of solid
dosage forms and production of injection and inhalation
dosage form


possibility of continuous operation

The advantages of the atmospheric

freeze drying with active hydrodynamics

The properties of the

pharmaceutical products




preserved of natural structure and nutrients



pre
-
specified particle size (nano
-

or microparticles)



high porosity



high specific and internal surface area of particles



solubility and bioavailability



free flowing powder



spherical particle shape






Comparison of spray drying and

atmospheric spray
-
freeze drying

Spray drying particles

Spray
-
freeze drying particles

Comparison of vacuum freeze
-

drying and

atmospheric spray
-
freeze drying



pre
-
specified particle size (nano
-

or microparticles)




high porosity




free flowing powder




spherical particle shape




product size and shape design for manufacturing


of solid dosage forms and production of injection


and inhalation dosage form




possibility of continuous operation


Shape and Structure of Particle

Spray drying particles

Vacuum
-
freeze drying particles

Atmospheric Spray Freeze Drying

as an Alternative


Advantages:



The result is a highly porous free flowing powder
(pellets) with instant
solubility
properties.



The high porosity of the pellets (up to 85%) and the
nanostructured internal surface is
ideal

for

the
formulation of novel drug delivery systems for the
lung
.

Atmospheric Spray Freeze Drying

as an Alternative


Advantages:



Process is faster due to the better heat transfer
and has a lower variability.



It is possible to combine the advantages of
Nano
-

and Microtechnology.

Atmospheric Spray Freeze Drying

as an Alternative


Advantages:



ideal for the
prepar
ation of

nanocomposite

pellets

for low water soluble drugs

to enhance
bioavailability of the drug.



ideal

for

the formulation of

temperature and
structure sensitive drugs such as
Biologicals

i.e.
Pharmaproteins such as Interferons, Insulin.

TECHNOLOGY TRANSFER

equipment selection

design and scaling
-
up

process flowsheet optimization

mathematical models

modeling tools


KINETICS




Drying

driving

force




Combined

heat

and

mass


transfer

inside

particle





Interface

processes


HYDRODYNAMICS

HEAT AND MASS TRANSFER
IN APPARATUS

DETERMINATION OF STABLE
OPERATION MODE

OPTIMIZATION
D
ESIGN SCALING
-
UP CONTROL










Modelling of the atmospheric

freeze drying with active hydrodynamics

Modeling of hydrodynamics, heat
-
and mass
-
transfer in apparatus








t
1
1
1
0




div
V
f
dm
M

;







t
m
f
div
f
V
f





2
0
;





t
C
div
C
V
f
dm
V
V
M





1
0
;
The equations of mass, concentration

preservation are:








1
d
V
dt
P
fm
f
dm
F
f
V
V
dm
k
k
M
M
1
1
1
1
12
1
1
2
1
0
0


















;
D
V
Dt
P
f
F
2
2
2
0
12
2
r
r
r
r






The equations of impulse preservation are:









;
dm
i
i
f
q
dm
T
T
f
a
4
dm
2
V
V
f
dm
V
V
f
fm
e
dt
d
P
dt
U
d
M
0
2
1
1
M
0
2
1
T
2
M
0
2
1
2
M
0
2
1
12
kl
1
kl
1
0
1
1
0
1
1
1
1
1
1








































2
1
2
1
T
2
0
2
2
0
2
2
2
2
2
i
i
f
T
T
f
a
4
Dt
D
P
Dt
U
D
mf












The equations of energy preservation are:





P
T
P
T
P
RT
d
dt
t
V
D
Dt
t
V
m
k
k
k
k
1
1
0
1
2
2
0
2
1
0
1
2
1
0
1
1
1
2
2
1
1
2















,
,
;
;
;
,
;
;















P

/
;
i

Additional correlations are:

Height
,
m

-0,3
-0,2
-0,1
0
0,1
0,2
0,3
0,4
0
0,2
0,4
0,6
0,8
1
1,2
1,4
Velocity
,
m/s


The drying kinetics

The driving force of process:

The

drying

rate
:


J

=


∙X

The

effective

mass

transfer

coefficient
:





=

Nu∙D/l


1

>

2

















V


The

main

influencing

factor

on

the

value

of

the

driving

force

of

atmospheric

freeze

drying

is

the

flow

of

injected

heat

into

the

product,

and

outflow

of

water

at

sublimation
.



1
2
1
2
2
1
2
1
1
2
2
T
2
V
V
T
1
T
1
i
T
T
X


























The mathematical model solution



The

solution

of

equations

system

allowed

to

investigate

the

hydrodynamic

and

temperature

regimes

(gas

and

particle

velocities,

temperature,

void

volume

etc
.
),

heat

and

mass

transfer

in

any

point

of

the

apparatus,

as

well

as

to

determine

the

drying

rate
.



Moreover,

on

the

basis

of

the

mathematical

model

it

is

possible

to

find

parameters

for

stable

operation

of

a

dryer,

for

example

the

height

of

a

fountain
.

The example of the drying kinetics

modelling

in apparatus II for d=150

洬mV
1inlet
=0,30 m/s

0
10
20
30
40
50
60
70
80
90
0
50
100
150
200
Time (min)
W, %
experimental data
freeze-drying stage calculated data
The apparatus design

and scale
-
up the process


The comparison of e
nergy efficiency of atmospheric
and vacuum
freeze
-
drying


0
0,05
0,1
0,15
0,2
0,25
0,3
0,35
0,4
0
200
400
600
800
1000
1200



Instantaneous energy efficiency



Time, min

Vacuum freeze drying

Atmospheric freeze drying

12
.
07
.
2005



7
th

WORLD

CONGRESS

of

CHEMICAL

ENGINEERING

24


the

atmospheric

freeze
-
drying

with

active

hydrodynamics

is

an

innovative

technology

for

production

of

pharmaceutical

nano
-

and

micro
-

powders

with

pre
-
specified

structure

and

properties



the

mathematical

model

based

on

the

mechanics

of

heterogeneous

media

and

non
-
equilibrium

thermodynamics

has

been

developed

and

verified

to

define

main

operation

parameters


on

the

basis

of

a

mathematical

model

the

drying

simulator

has

been

developed



also,

a

energy

efficiency

analysis

of

atmospheric

freeze

drying

was

carried

out
;

in

comparison

with

classical

freeze
-
drying

it

is

more

energy

efficient



the

approach

proposed

allows

modeling,

design

and

control

of

the

processes

described


Conclusions

TECHNOLOGY TRANSFER AND
PROMOTION


Conferences


Seminars


Round tables


Exhibitions


Publications


Website






The Third Russian
-
Swiss seminar
“Pharminnovations”

5
-
6

December, 2006

HÜTTLIN GmbH


(Germany)

NOVARTIS


(Switzerland)


BIOTECHNOLOGY 2009


16
-
20 March


«
Quality management


key factor in the
development of pharmaceutical industry
»

Our Partners

Московская медицинская
академия им И.М. Сеченова

Join us!

Welcome to Russian
-
Swiss Center!

Thank you for your attention!