New Technologies - APV

2 nd APGI COATING WORKSHOP
April 17, 2013
Lille, France
See page 3
3 rd Conference on Innovation
in Drug Delivery
September 22-25, 2013
Pisa, Italy
See page 3
2012
MAURICE-MARIE JANOT
AWARD
attributed to
Prof. R. Gurny
See page 5
2012
N°27
Issue 1
See page 2
GAZETTE
www.apgi.org

APGI board
Président : Pr. Juergen Siepmann
Vice-Président : Dr. Vincent Jannin
Trésorière : Dr. Marie-Pierre Flament
Secrétaire : Pr. Odile Chambin
Membre : Dr. Maria Teresa Peracchia
Membre : Dr. Karine Andrieux
APGI council
Pr. Philippe Arnaud
Dr. Karine Andrieux
Dr. Emeline Berlier
Dr. Amélie Bochot
Dr. Marie-Alexandrine Bolzinger
Dr. Kawthar Bouchemal
Dr. Sandrine Bourgeois
Dr. Régis Cazes
Dr. Renée de Challemaison
Pr. Odile Chambin
Dr. Caroline Chemin
Pr. Dominique Chulia
Dr. Michel Deleers
Dr. Marie-Pierre Flament
Dr. Alexandre Gil
Dr. Vincent Jannin
Dr. Caroline Lemarchand
Dr. Maria-Teresa Perrachia
Pr. Véronique Préat
Dr. Christel Raffournier
Dr. Florence Siepmann
Pr. Juergen Siepmann
Dr. Céline Valéry
Pr. Pascal Wehrlé
SOMMAIRE
CONTENT
Editorial 1
International News 2
Skin & Formulation 4 th Symposium 2
2 nd APGI Coating workshop 3
3 rd Conference on Innovation in Drug Delivery 3
8 th World Meeting 4
Maurice-Marie Janot Award 2012 5
JDDST Awards 6
9 th World Meeting 6
In Memoriam –Professor André Moës 7
Master of advanced studies in Toxicology 8
New Technologies 8
Micronized APIs in direct compression 8
Inhalation Technology 12
Agenda 16
XXXXXXXXXXXXXXXXXXXXXXXXXXX
Call for APGI Thesis award 2011
This annual award, granted jointly by SANOFI and APGI, recognize theses written as the culmination
of the Pharmaceutical Technology PhD programme.
If you have defended your PhD thesis in 2011, you can apply for the APGI Young Investigator
Award 2011. The amount of the Prize is 1500 € and it will be awarded during an international
congress organized by Apgi (travel expenses to the congress will be deducted from the amount of
the Prize). No registration fee for the conference will be charged. To apply, please send, by September
10, 2012, three copies of your thesis manuscript (hard copy only) and a short curriculum
vitae to the APGI secretariat: 5 rue Jean-Baptiste Clément,
FR-92296 Châtenay-Malabry, Cedex, France.

Dear Colleagues
The 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology
in Istanbul was a great success with more than 1300 participants from all over the
world (more than 60 countries) and more than 900 submitted abstracts. This outstanding
event was jointly organized with our friends of the ADRITELF and APV. And we are already
preparing and looking forward to the 9 th Meeting in this more and more successful series,
which will be held in Lisbon, Portugal, on 31 March - 3 April 2014.
The next major APGI event is the 4 th "Skin & Formulation, 4 th Symposium", which will take
place on 4-5 June 2012 in Lyon. For the first time it will be jointly organized together with the European Centre of
Dermocosmetology (CED). More than 100 abstracts have been submitted and about 250 participants are expected.
Furthermore, do not forget to note in your agendas that the 2nd APGI Coating Workshop will be held in Lille, on 17
April 2013, and the 3 rd Conference on Innovation in Drug Delivery on 22-25 September 2013 in Pisa, Italy, with a
special emphasis on "Advances in Local Drug Delivery".
In the name of the APGI I would like to sincerely thank Prof. Véronique Rosilio, University of Paris-Sud, for her tremendous
work as Editor-in-Chief of the APGI Gazette. It was always a great pleasure to work with her. I would like to welcome
the new Editor-in-Chief: Dr. Youness Karrout, University of Lille. Dr. Florence Siepmann will continue to do the
type setting and layout.
Juergen Siepmann
President of APGI
3
1
Editorial

Skin & Formulation 4 th Symposium
June 4-5, 2012, Lyon Congress Centre, Lyon, France
For the first time the APGI organizes the "Skin & Formulation Symposium"
jointly with the European Centre of Dermocosmetology (CED) .
It will be the fourth event in this highly successful series of meetings,
which was held in Paris (2003) and Versailles (2006 and 2009) before.
On June 4-5 the beautiful city of Lyon, recognized by the UNESCO as
part of the world heritage, will host this outstanding event. More than
100 scientific abstracts have been submitted and about 250 participants
from all over the world are expected.
The "Skin & Formulation" symposia
have become a unique discussion
forum for pharmacists, biologists,
chemists and physicians on the interactions
between the skin and formulations
applied to it. The various aspects
of topical and transdermal applications of pharmacologically and
cosmetically active compounds will be presented and discussed.
In Lyon, special emphasis will be placed on the following topics:
• Skin structure and biology
• In silico, in vitro, and in vivo evaluations
• Formulation trends for topical delivery
• Powder technology
There will be a mixture of plenary and
invited lectures as well as short communications
selected from submitted abstracts.
Special highlights include: Prof. J.
Bouwstra (Leiden University) "The skin
barrier function of patients with atopic
eczema"; Dr. M. Haftek (University
Claude Bernard Lyon)
"Compartmentalization of the human
stratum corneum by persistent tight
junction like structures"; Prof. A. Baillet-
Guffroy (University of Paris Sud) "Raman and IR spectroscopy for cutaneous
lipids and skin barrier function investigation"; Dr. T. Förster
(Henkel, Germany) "Tissue engineering: leading edge technology for
cosmetic innovations"; Prof. P. Humbert (University of Franche Comté)
" New advances in skin absorption design"; Prof. J.E. Riviere (North
4 2
International News
Carolina State University) "Modeling and prediction of skin absorption
from complex formulations"; Prof. A. Patzelt (Humboldt University)
"Follicular penetration"; Prof. N. Monteiro-Riviere (North Carolina
State University) "Nanoparticles and skin interactions: safety evaluation";
Dr. T. Oddos (Johnson & Johnson Santé Beauté) "Effect of formulation
on skin gene expression"; Dr. E. Perrier (LVMH Parfums et
Cosmétiques) "New trends in skin care formulation and sensory aspects";
Prof. O. Glatter (University of Graz) "Physical chemistry of nano
-structured emulsions and gels"; Dr Chevalier (LAGEP, University
Claude Bernard Lyon) “Pickering emulsions: A new formulation for
drug delivery to skin”; Prof. S. Daniele (University Claude Bernard
Lyon) "Smart functional nano-materials synthesis from molecular
engineering"; Dr. E. Prouzet (University of Waterloo) "Integrative chemistry
applied to inorganic materials
for cosmetics: a "nouvelle cuisine" in
old pots?"; Dr. A. Burr (CEMEF, Mines
de Paris) "Smaller than small: Optics,
appearance, and nanoparticles"; Dr.
M. Imazeki (Miyoshi Kasei) "The
development of a structural-colored
powder and its application"; Dr. S.
Bureau (Chanel) "Basics and process
innovation for make-up formulations".
Furthermore, an exhibition will be
organized in the poster-lunch/coffee break area.
The organizers are very grateful for the support of this meeting by
Gattefossé (main sponsor), 3M, Heath Scientific, Bertin Technologies
Seppic, Apricus Bio-NexMed USA and Sanofi.
Fort more detailed information, please have a look at the meeting's
website: http://www.apgi.org/Skin4.htm.
We are all looking forward to meeting you in this very typical French
city!
On behalf of the organizing committee

2 nd APGI Coating Workshop
April 17, 2013, University of Lille, Lille, France
Following the great success of the 1st APGI Coating Workshop in 2008,
it is our pleasure to announce the 2nd workshop of this kind in Lille,
France, on 17 April, 2013.
The one day event will be dedicated to the coating of pharmaceutical
dosage forms and address scientists from all over the world, in particular
those working in the pharmaceutical industry. A variety of lectures
will be given by academic and industrial speakers, pointing out the
challenges to be faced and explaining strategies for an efficient and
successful product development.
The worldwide leading researchers in the field, including Prof. R. Bodmeier
(Freie Universitaet Berlin), Prof. A. Gazzaniga (University of
Milan), Prof. A. Basit (University of London), Prof. T. Rades (University
of Copenhagen), Dr. R. Chokshi (FMC Biopolymer), Dr. V. Janin
(Gattefossé), Dr. V. Geiselhart (BASF), Dr. A. Rajabi-Siahboomi
(Colorcon), and Dr. B. Skalsky (Evonik) will give invited lectures and
discuss with the audience.
Furthermore, a series of practical demonstrations will give insight into
the different types of coating equipments (e.g. Glatt, GEA and Procept),
excipients available on the market and helpful film coating characterization
techniques (e.g. Sotax and Malvern).
In addition, an industrial exhibition will allow getting familiar with the
newest developments in this highly challenging field.
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International News
The entire spectrum, ranging from: engineering aspects during the
coating process, the portfolio of commercially available coating polymers,
the underlying drug release mechanisms, characterization
methods for thin film coatings, drug release measurement techniques
as well as potential pitfalls and hurdles to be overcome during product
development will be addressed.
As practical demonstrations are included, the maximum number of
participants is limited to 150.
We are looking forward to seeing you in Lille!
Lille can be easily reached by train (TGV
and Eurostar: 30 min from Brussels, 1 h
from Paris, 1.2 h from London), by plane
(Lille Lesquin Airport, or Paris Charles de
Gaulle Airport – 50 min by train) and by
car.
For more detailed information, please visit
the meeting's website:
http://www.apgi.org/coating_WS.
3 rd Conference on Innovation in Drug Delivery
September 22-25, 2013, Congress Center of Pisa, Pisa, Italy
Dear members and friends,
After the success of the 1st and the 2nd
conference on “Innovation in Drug delivery”
(respectively, in Naples in 2007 and in
Aix-en-Provence in 2010), together with
our ADRITELF friends the decision was
naturally taken to pursue the organization
of the series, and I am pleased to announce
that the 3rd conference will take
place in Pisa, Italy, on September 22-25,
2013 at the Congress Center of Pisa. This time, the symposium will be
focused on Advances in Local Drug Delivery, and will cover all the
topics related to local drug delivery, including drug targeting, topical
administration, in situ forming systems as well as biomaterials. The
scientific committee is currently elaborating the program, and we
On behalf of the
organizing committee
should be able to announce soon the plenary lectures and the invited
speakers. And of course we will design an attractive social program (do
not forget that Pisa is located in the superb Tuscany region).
Block the dates, to be sure not to miss this event!
Maria Teresa Peracchia
Member of the APGI board
Member of the Organizing Committee of Pisa 2013

6
International News
The 8 th World Meeting on Pharmaceutics,
Biopharmaceutics and Pharmaceutical Technology
was a great success !
On March 19-22 the 8th World Meeting on Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology was held in Istanbul, jointly
organized with the APV and ADRITELF.
The meeting was an outstanding success with more than 1300 participants
coming from all over the world (all 5 continents, more than 60
countries) and more than 900 submitted abstracts.
Special highlights included the comprehensive and exciting plenary
lectures given by Prof. P. Couvreur, Dr. A. Hussain and Prof. H.L. Offerhaus.
Prof. Couvreur clearly and enthusiastically pointed out the
strengths and limitations of advanced nanomaterials allowing for drug
delivery and targeting.
In addition, four parallel sessions of invited talks and short presentations
from submitted abstracts gave an overview on the most recent
advances and newest trends in our field. This was also true for the
highly remarkable poster sessions and the (fully booked) industrial
exhibition "ResearchPharm", which presented novel products in the
area of pharmaceutical ingredients, processing equipment, analytical
technologies, medicinal products, medical devices, contract manufacturing
and recent publishing.
Special emphasis was placed on industrial related topics, in particular:
Drug delivery to special populations: pediatrics and geriatrics, drug
counterfeiting, Quality by Design, oral controlled release products,
therapeutic vaccination, oral products for poorly water soluble drugs,
therapeutic protein modifications and biological relevance, industrial
manufacturing of solid dosage forms, nanotechnology and special
delivery devices.
The special mix of oral and poster presentations together with the
industrial exhibition allowed for intensive exchange between the participants
and the initiation of fruitful cooperation between university
and industry.
4
Prof. Jürgen Siepmann (left) , Prof. Jörg Breitkreutz (middle)
& Prof. F.ranco Alhaique (right)

Istanbul’dan Merhaba !!!
About us
We are fifteen Master’s
students in Pharmaceutical
Technology and Biopharmacy(www.physpharmtech.upsud.fr)
at the Faculty of
Pharmacy in Chatenay-
Malabry (Paris). We have
different educational backgrounds, but we have joined forces to develop
a common project in relation with our future profession. Thus we
decided to regenerate the Galen’idea association (http://
galenidea2012.free.fr) and to participate in the 8th World meeting in
Istanbul...
Travel planning
In order to make this journey, we searched for sponsors, we developed
a website and we advertized our Master’s degree in the pharmaceutical
industry forum in Chatenay-Malabry. Everyone in the year group
contributed something to this project. Thanks to the involvement of
Prof. Fattal (director of UMR CNRS 8612), Prof. Siepmann and to sponsorship
from pharmaceutical companies, this project became reality.
Congress
We had the pleasure of attending the 8th World Meeting on Pharmaceutics,
Biopharmaceutics and Pharmaceutical Technology, held in
Istanbul (Turkey) from 19 to 22 March 2012. This event was the oppor-
Maurice-Marie Janot Award 2012
Prof. R.obert Gurny
Prof. Maurice-Marie Janot was an outstanding scientist who worked at
the College of Pharmacy at the University of Paris. Importantly, his
research was highly interdisciplinary and he was the mentor of 38
associate and full professors and of 13 CNRS researchers. Former
laureates of this highly prestigious price include Prof. Stanley S. Davis,
Prof. Joseph R. Robinson, Prof. Hitoshi Sezaki, Prof. Daan J.A. Crom-
5
7
International News
tunity for us to discover the organization of an international congress,
to attend some very interesting lectures and interact with scientists
from all around the world. Some students had the chance to contribute
to the organization of this event. Various topics were discussed,
including oral controlled release products, oral products for poorly
water soluble drugs, solid dosage form, analytics, drug nanocarriers,
paediatrics and geriatrics… Among oral presentations, the plenary
lecture of Mr Couvreur about “Strength and limitations of nanomaterials
for drug delivery and targeting” was very interesting. The lectures
were opportunities to think about new experiments, to discover new
materials and to open our minds to issues of methodology. For example,
Grzegorz Garbacz presented material which showed how the intra
and intervariability could be considered to obtain reliable pharmacokinetics:
using a pressure flask, stirrers, buffers and different stress test
programs, he showed the impact of the tablet’s dissolution in the case
of a fast or slow gastric emptying. We could all find inspiration for our
different laboratory projects from the symposia and discussion at the
additive manufacturers’ stands. To put our participation to the conferences
to good use, we prepared reports of the conferences and thanks
to the exhaustive poster session, everyone could improve their
knowledge and meet colleagues.
To conclude, this enriching experience allowed us to forge friendly
relationships with each other and to discover the scientific world at an
international dimension in a fabulous city!
We already planned to meet again in Lisbon in two years!
Prof. Robert Gurny
is the laureate of the Maurice-Marie Janot 2012 Award
Prof. Robert Gurny from the University of Geneva received the
Maurice-Marie Janot 2012 Award during the 8th World Meeting on
Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology in
Istanbul.
This outstanding recognition rewards an individual researcher who
published original and innovative work in the domain of pharmaceutics,
biopharmaceutics and pharmaceutical technology. The Award is
given by the Association Française des Enseignants de Pharmacie
Galénique and the APGI.
melin, Prof. Francis Puisieux, Prof. Hans E. Junginger, Prof. Thomas
Kissel, Prof. Paolo Colombo, Prof. Alexander Florence, Prof. Patrick
Couvreur, and Prof. Nicholas Peppas.
An international jury, composed of 40 members and headed by Prof.
Paolo Colombo (University of Parma, Italy), selected the 2012 laureate.

Professor Gurny works at the School of Pharmaceutical Sciences at the
University of Geneva. He is Editor-in-Chief of the European Journal of
Pharmaceutics and Biopharmaceutics and a world-wide know pioneer
in the field of novel drug carriers and drug targeting. So far, he published
his findings in more than 330 peer reviewed articles, more than
35 patents and supervised more than 40 PhD theses. During the open-
Two new JDDST Awards
Two new awards of the Journal of Drug Delivery
Science and Technology (JDDST) have been
introduced this year:
Journal of Drug Delivery Science and Technology
Best Paper Award
Journal of Drug Delivery Science and Technology
Most Cited Paper Award
Both prices will be attributed every year. The JDDST Best Paper Award
recognizes the most valuable original research article and is selected
by an international committee of scientific experts. It is attributed in
the year following the publication of the respective paper. For
example, this year the award for the best paper published in 2011 was
attributed.
In contrast, the JDDST Most Cited Paper Award is attributed 2 years
after publication of the respective article in order to allow for citation
during at least one year. For example, this year the award for the most
cited paper published in 2010 was attributed.
In continuation of the very
successful past scientific meetings
in Budapest, Paris, Berlin,
Florence, Geneva, Barcelona,
Malta, and Istanbul the ADRI-
TELF, APGI and APV will jointly
organize the 9th World Meeting
on Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology in Lisbon, Portugal, on 31
March - 3 April, 2014.
Continuing the concept of combining 4 parallel sessions of invited oral
presentations & short talks selected from submitted abstracts, as well
as poster presentations and an industrial exhibition, also the next
World Meeting will offer an excellent opportunity to network and get
8 6
International News
ing ceremony of the 8th World Meeting on Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology he gave an exiting Maurice-
Marie Janot Award Lecture on innovative drug carriers.
The Maurice-Marie Janot 2012 Award was very kindly sponsored by:
The two first laureates of these highly prestigious recognitions were:
Best Paper Award 2011
A. Puccio, F. Ferrari, S. Rossi, M.C. Bonferoni, G. Sandri, C. Dacarro, P.
Grisoli, C. Caramella. Comparison of functional and biological properties
of chitosan and hyaluronic acid, to be used for the tratment of
mucositis in cancer. Journal of Drug Delivery Science and Technology,
2011, 21, 241-247.
Most Cited Paper Award 2010
C. Alvarez-Lorenzo, F. Yanez, A. Concheiro. Ocular drug delivery from
molecularly-imprinted contact lenses. Journal of Drug Delivery Science
and Technology, 2010, 210, 237-248.
The winners were recognized during the Opening Ceremony of the 8th
World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical
Technology in Istanbul.
The JDDST is the official APGI journal.
Prof. Dominique Duchêne Prof. Juergen Siepmann
Editor-in-Chief Co-editor
9 th World Meeting on Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology
March 30-April 3, 2014, Lisbon, Portugal
an update on the current state of the art in Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology.
The scientific program will be elaborated by the 2014 World Meeting's
Programme Committee, whose members are: Dr. Marco Adami, Prof.
Franco Alhaique, Prof. Joerg Breitkreutz, Prof. Anna Maria Fadda, Prof.
Juan M. Irache, Dr. Vincent Janin, Prof. Karsten Maeder, Prof. Joao
Pinto, Dr. Andreas Rummelt, and Prof. Juergen Siepmann.
Please do not hesitate to suggest potential session topics and invited
speakers.
We are looking forward to welcoming you in Lisbon!
On behalf of the organizing committee

Hommage au Professeur André Moës
par Karim Amighi, Doyen de la Faculté de Pharmacie de l’Université Libre de Bruxelles
Prof. André Moës
André Moës est décédé le lundi 30
avril dernier au terme d’une longue et
accablante maladie, profondément
injuste pour un Homme dont l’excellence
scientifique fut unanimement
reconnue. En tant que Doyen de sa
Faculté, mais aussi en qualité d’ancien
élève, j’ai le privilège d’évoquer
brièvement son parcours
professionnel particulièrement
riche, sans cependant me priver de
souligner quelques traits marquants
de sa forte personnalité.
Né le 7 décembre 1938 sur les terres liégeoises auxquelles il restera
fidèlement attaché, il obtint son diplôme de pharmacien de l’Université
de Liège en 1961. Elève des Professeurs Denoël et Jaminet, les deux
pionniers de la pharmacie galénique moderne en Belgique, André Moës
présenta une thèse de doctorat en février 1970. Il débuta sa carrière
académique à l’Université de Liège avant de rejoindre l’Université Libre
de Bruxelles (ULB) pour y fonder en 1980 un tout nouveau laboratoire
résolument orienté vers un enseignement moderne et de qualité et y
développer des axes de recherches novateurs dans le domaine des
formes à libération contrôlée et/ou ciblée pour les voies orales et
parentérales.
Son courage hors pair et son acharnement sans limite au travail, ses
larges compétences, sa rigueur scientifique et son souci du travail bien
accompli ont très vite fait l’unanimité dans le monde académique et
scientifique et auprès des professionnels du métier. Il a été pour un
grand nombre de personnes ayant eu le privilège de le côtoyer ou de
bénéficier de ses enseignements, un maître admiré et respecté. Ses
charges d’enseignement énormes concernaient non seulement le domaine
de la pharmacie galénique et de la biopharmacie, mais aussi la
législation et la déontologie pharmaceutique, la technologie pharmaceutique
industrielle, la technologie des formes cosmétiques, ainsi que
celle des médicaments en milieu hospitalier. Ses qualités de pédagogue
ont notamment été mises à profit à de nombreuses reprises par d’autres
Facultés et Universités, en Belgique et à l’étranger, notamment
dans le cadre de programmes d’enseignement Erasmus consacrés aux
nouvelles formes de délivrance des médicaments, ainsi qu’en pharmacocinétique
et en biopharmacie.
De nombreux étudiants, tout à fait enthousiasmés par ses qualités de
pédagogue hors norme et sa rigueur scientifique décidèrent d’entreprendre
la réalisation d’une thèse de doctorat sous sa direction. Son
héritage et la dynamique de recherche qu’il a insufflé ont permis de
pérenniser les activités de recherche du laboratoire de pharmacie
galénique de l’ULB; ainsi pas moins de 24 chercheurs ont pu défendre
leur thèse de doctorat depuis 1986, date à laquelle la première thèse
de doctorat réalisée sous sa direction fut défendue, et dix autres sont
actuellement en cours.
9 7
Le caractère innovant des différents projets de recherche qu’il a initiés,
combiné à la formation polyvalente dont les chercheurs ont pu bénéficier
sous sa direction, leur ont permis d’essaimer à travers le
monde et d’accéder à des postes importants, dans des créneaux aussi
variés que sont le monde académique (Universités de Montréal, Lisbonne,
Ouagadougou - Burkina Faso), l’industrie pharmaceutique (Eli
Lilly, GSK, Capsugel, UCB, SMB), ainsi qu’auprès d’organisations internationales
telles que l’OTAN.
Les témoignages de reconnaissance à son égard de la part du monde
scientifique, du monde industriel et des organismes gouvernementaux
sont innombrables. Ses travaux, aussi abondants que diversifiés, dans
les domaines de la physico-chimie appliquée aux formes pharmaceutiques,
de la technologie pharmaceutique et de la biopharmacie sont
encore et toujours cités en référence dans un grand nombre de revues,
livres et réunions scientifiques spécialisées.
Son autorité dans le domaine de la pharmacie galénique l’a amené à
faire partie de comités de nombreuses sociétés scientifiques et organismes
divers. Son expertise dépassait largement les frontières de la
Belgique, il était notamment fort attaché à ses collaborations, avec le
monde académique et scientifique en France, en Italie, en Espagne et
en Grande Bretagne. Il a noué à travers ses collaborations de profondes
amitiés qui l’ont notamment amené à participer en tant que membre
actif à l’Association Française des Enseignants de Pharmacie Galénique,
comme membre du jury du prestigieux prix « Lecture Marie-Maurice
Janot » et enfin en tant que membre correspondant à l’Académie Nationale
de Pharmacie de France.
Au-delà du savant, André Moës fut également un grand humaniste. Il
s’épanouit et se révéla pleinement à l’ULB, dans l’université du Libre
Examen, dont les conceptions philosophiques correspondaient à ses
valeurs les plus profondes. Sous des dehors parfois sévères, appuyés
par sa grande stature, son maintien rigide, son exceptionnelle éloquence
et ses cheveux rapidement blanchis par l’âge, il savait se montrer
très disponible et attentif aux autres, fussent-ils ses élèves ou ses
collègues, et faisait montre d’une grande générosité envers tous ceux
qui venaient le solliciter. Témoignent aussi de sa personnalité, son
ouverture d’esprit et son attachement à la coopération au développement
et à l’accueil d’étudiants d’origines culturelles aussi lointaines
que variées. Sa participation à la coopération au développement avec
le Burkina Faso a contribué, en outre, à la mise sur pied d’un cycle
d’enseignement complet au sein de la Faculté des Sciences de la Santé
de l’Université de Ouagadougou et au développement d’une unité de
fabrication de médicaments.
Au nom des Autorités de l’ULB et de mes collègues de la Faculté de
Pharmacie, je voulais tout particulièrement lui témoigner notre
profonde reconnaissance. Son souvenir restera à jamais gravé dans nos
mémoires.
Prof. Karim Amighi

Micronised APIs in direct compression
Master of Advanced Studies in Toxicology
Université de Genève, Switzerland
Information | Online Registration (before August 15, 2012)
Prof. Eric DOELKER | T. +41 (0)22 379 63 36 | mas-toxicology@unige.ch
www.unige.ch/formcont/toxico
Micronised APIs in direct compression
H. Leonhard Ohrem, Roberto Ognibene, Thorsten Wedel
Introduction
Over the last decades, newly developed drug molecules are becoming less and less water-soluble and, as a result, strategies to increase this solubility are
required. One means of doing this is to enlarge the surface area by micronization of the active pharmaceutical ingredient (API). If this then has to be formulated
as a solid dosage form, problems will arise in obtaining and maintaining a homogenous mixture with other excipients.
Another reason for using micronized API is the formulation of highly potent drugs which require low dosage. To evenly distribute less than 1% API within a
solid formulation is very difficult. For this reason, many formulators tend to prefer wet granulation over the much cheaper and easier direct compression.
A purely physical mixture based on statistical distribution often does not remain homogeneous. For this reason many formulators switch to more expensive
wet or dry granulation processes instead of direct compression or sachet formulations.
According to the literature a mixture is most likely to be stable if the particles of the API and excipients are in the same size range [1]. However, for handling
reasons it is mandatory for the mixture of excipientsand API to be in a granulate form rather than in powdered form.
Thus, the aim of this study was to evaluate whether such APIs could form stable mixtures with larger excipientparticles and undergo a DC-tableting process
leading to good content uniformity. An earlier study has shown the stability of so-called ordered mixtures with spray-dried sorbitol and much smaller API
particles [2, 3] . Hersey first introduced the concept of ordered mixtures to explain the behavior of interacting particles in a powder mixture.[4]
The cited literature dealt with spray-dried sorbitol which was at that time one of the few direct compressible excipients. Nowadays mannitol is much more
frequently used, especially for ethical pharma developments due to its inertness towards both the patient and the API, its low hygroscopicity and its fast
release qualities. Therefore, this study focuses on different DC-grade mannitols available on the market.
10 8
New Technologies
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Micronised APIs in direct compression
Materials and Methods
Two types of spray-dried DC-mannitol were used
(DC-Mannitol A and Parteck® M) and one type of
granulated mannitol (DC-Mannitol B; see Table 1
for details). The model APIs were ascorbic acid, as
an example for a hydrophilic compound, and riboflavin,
as a hydrophobic compound. Both APIs
were micronized in a pin mill before use (particle
sizes are given in Table 1).
API-mannitol mixtures (batch size 300 g) were
prepared using a Turbula® T2C shaker-mixer (Willy
A. Bachofen AG Maschinenfabrik, Basel, Switzerland).
To evaluate the quality of mixing, the homogeneity
was measured by taking 6 samples from
the mixtures at defined sampling locations after a
specified period of mixing time (2, 5, 10, 20 and 30
minutes). The API content in each sample was
analyzed (n = 18). For ascorbic acid, the content
was determined through a volumetric analysis by
titration with an iodine solution (TitriPUR®, Merck
KGaA, Darmstadt, Germany), and a accuracy of
measurement with a relative standard deviation of
0.12%. The riboflavin content was determined spectrophotometrically at
444 nm according to Ph.Eur.[4]
The relative standard deviation (RSD) of the API concentration was then
examined as a function of mixing time (Fig. 1 and 2).
To challenge the mixture stability and to show the strength of adsorption of
the API in low-dose formulations, API – DC-mannitol mixtures with a drug
Results
Excipient/API Supplier
Parteck® M200
Cat. No. 100419
DC-Mannitol A
spray dried
DC-Mannitol B
granulated
Ascorbic acid*
Cat. No. 500078
Riboflavin*
Cat. No. 500257
The reduction of the relative standard deviation of the measured APIconcentrations
shows how the mixture approaches homogeneity with increased
mixing time (see Fig. 1). A time of 30 min was chosen as sufficient
to consider the mixture of DC-mannitol with micronized ascorbic acid as
homogeneous (rel. standard deviation = 0.67%). The mixing behavior of a
blend is dependent on the API and the excipient as well as on mixer type,
scale and the degree of filling of the mixer. As the latter parameters were
constant for all assessed blends, differences in homogeneity must be
attributed to either the API or the excipient. In this case, the micronized
hydrophobic particles of riboflavin tend to reagglomerate during mixing.
Therefore the homogeneity first decreases before the mixture reaches a
steady state (Fig. 1).
The resulting mixing time of 30 min seems to be rather high. It has to be
taken into account that this small lab scale mixing unit is certainly not optimized.
More importantly, the micronized API granules have a tendency to
aggregate due to their high surface energy. This binding force has to be
overcome and replaced by an alternative binding force – adsorption and
van-der-Vaals interaction with the carrier surface. This is a dynamic equilibrium
process and takes longer than a statistical distribution of different
particles in space.
The comparison of different DC-mannitols at optimum mixing time reveals
differences in the homogeneity of their mixtures with micronized ascorbic
acid and riboflavin (Fig. 2). Clearly, greater homogeneity can be obtained
11
New Technologies
Table 1: Physical characteristics of excipients and APIs (*) used.
content of 1 and 3% were placed in an Alpine® air jet sieve A 200 LS
(Hosokawa Alpine AG, Augsburg, Germany) and analyzed for their drug
content after 15 min of airflow. The mesh size was 40 µm and the vacuum
pressure 2000 mPa.
As a more relevant example, the feasibility of a stable direct compression
process was investigated using a water-sensitive low-dose drug in a pharmaceutical
formulation (see Section R&D case study for details and results).
9
Particle Size
Laser Light Diffraction
Dv50
[µm]
Crystal
Modification
Surface Area
Acc. BET-Method
[m 2 /g]
Merck KGaA 196.8 β 2.89
A 143.6 α 0.60
B 286.0 β 0.50
Merck KGaA 4.52 N/A Not determined
Merck KGaA 1.72 N/A Not determined
Figure 1: The relative standard deviation of the API content in
relation to the mixing time of API-Parteck® M samples (drug load
1% w/w).
for a hydrophilic API than for a hydrophobic API. Here the reduced attraction
forces between a hydrophobic API and a hydrophilic carrier means that

Micronised APIs in direct compression
aggregation of API particles predominates over binding to the carrier surface.
This is not a surprising observation which can be applied to allexcipients.
However, Figure 2 shows that there are also differences in the uniformity
of the mixtures obtained with the different carriers for a given API.
The best homogeneity for both APIs was found for the excipient with the
highest surface area (Parteck® M, Table 1). This indicates a correlation
between BET surface area and/or pore volume and the achievable homogeneity.
However, there are also significant differences between spray-dried
and granulated DC-mannitol although they have similar BET-surfaces (Fig 7).
So, both the quality of the surface structure and the quantitative size of the
surface area seem to be relevant.
Figure 2: Relative standard deviations of the API concentration in
samples containing a model API and different DC-mannitols as
excipients.
To test the strength of the adsorption of API to the excipient surface the
remaining concentration of ascorbic acid and riboflavin was measured after
15 min on an air jet sieve. In this set-up, fine API particles that were not
strongly adsorbed would be lost. A recovery of 100% would mean complete
adsorption of the API to the carrier while a recovery of 0% would indicate
no absorption to the carrier.
Figure 3: Comparison of the API concentration measured after
15 min in an air jet sieve using either granulated DC-Mannitol B,
spray-dried DC-Mannitol A or Parteck® M as excipient for model
drugs ascorbic acid or riboflavin.
12 10
New Technologies
A much stronger adsorption was found for the spray-dried DC-mannitols
compared with the granulated quality (Fig. 3). For low API concentrations of
a hydrophilic drug, the two spray-dried mannitols showed similar results.
Using higher API loads, it was demonstrated that the higher surface area of
Parteck® M showed a higher binding capacity. This effect was confirmed
with a hydrophobic API, riboflavin. These results may again be explained by
the different surface structure of the investigated excipients. The lower
recovery of the hydrophobic API again confirms a weaker surface adsorption
of this class of API.
Figure 4: SEM image showing a mixture of Parteck® M 200 and
micronized ascorbic acid (drug load 1% w/w).
Figure 5: SEM image showing a mixture of spray dried DC-
Mannitol A and micronized ascorbic acid (drug load 1% w/w).
To visualize the API distribution on the carrier surface, SEM was employed.
Figure 4 shows the SEM image of a mixture of ascorbic acid and Parteck® M.
The micronized API particles are readily identifiable due to the different
crystal structures of API and carrier (coloration performed manually). The
API crystals were found within the pore structure of the much larger excipient
particles. Figure 5 shows the SEM image of spray-dried DC-Mannitol A

Micronised APIs in direct compression
and ascorbic acid. Here, fewer areas suitable for the absorption of the API
are present. The overall surface is less structured. A similar distribution on
the carrier surface was determined for the hydrophobic model drug riboflavin
(Fig. 6).
Figure 6: Mixture of Parteck® M 200 with micronized riboflavin
(drug load 1% w/w). Light microscope with 40x magnification.
The yellow particles of API are clearly visible in the porosity of
the carrier surface.
The importance of the surface area and the pore volume of the additive for
the homogeneity of the mixture was demonstrated. Next, the surface area
and porosity of various additives for direct compression were analyzed
using the BET method (nitrogen adsorption). Since the API is adsorbed to a
porous surface, the observed differences between the excipients may give
rise to different behavior in the adsorption of micronised APIs (Fig. 7).
This study has shown that stable mixtures of much smaller micronized API
particles with DC-excipients can be achieved. Is this suitable for a direct
compression process in a real formulation?
Figure 7: Comparison of the surface area and pore volumes of
different excipients for direct compression.
13 11
New Technologies
R&D Case Study: Results from a Field
Testing
The question of whether low-dose pharmaceutical formulations with micronized
API can be prepared by a DC process was tested using a watersensitive
R&D-API at only 0.4% in the final dosage form (0.5 mg API in 120
mg tablet). Wet granulation could not be applied, because of the watersensitivity
of the API. So the micronized API (Dv50 10 µm) was premixed for
30 minusing a Turbula® T2C shaker-mixer with 15% of the total amount of
DC-grade mannitol Parteck® M (Dv50 200 µm), then mixed with the rest of
the formulation (Fig. 8). A test run of 2 h on a Korsch Pharmapress PH230
rotary press (Korsch AG, Berlin, Germany) was performed at two different
rotation speeds (40’000 and 80’000 T/h). The tablets were assessed for
their weight, hardness and disintegration time.
This result was surprisingly good, as constant values were detected for
tablet weight (RSD 0.6 – 0.9%), tablet hardness (RSD 4.1%) and disintegration
time (Table 2). Content uniformity was measured to be ± 1.8 %.
Figure 8: Composition of the pharmaceutical formulation used
for the R&D case study.
Table 2: Comparison of tablets manufactured at different speeds of the
rotary press.
Tablet weight
Conclusion
40‘000 Tablets/h 80‘000 Tablets/h
120.1 mg (RSD
0.6%)
118.8 mg (RSD 0.9%)
Tablet hardness 178 N (RSD 4.1%) 173 N (RSD 4.1%)
Disintegration time 3'25'' 3'22''
Although the concept of ordered mixtures has been extensively studied and
reported [6,7,8,9], little was known about the underlying mechanisms and
rationale. The results show clearly that the effect of ordered mixtures can
be seen with DC-mannitols as a function of surface area and structure. The
effect is greatest with for spray-dried qualities with a porous surface structure.
A large surface area is necessary for a good binding capacity. Stable

Inhalation technology
mixtures are not only achieved with components of similar particle sizes as
reported in the literature. It is also possible to achieve a stable mixture of
micronized API particles (< 15 µm) with a DC-mannitol with a mean particle
size of 200 µm. The stability is the result of an adsorptive binding force
strong enough to withstand mechanical separation forces. This was successfully
demonstrated for both hydrophilic and hydrophobic APIs. This result
confirms the feasibility of direct compression for low-dose applications with
a very acceptable content uniformity, as the example shows. It is also advantageous
to use micronized APIs at higher concentrations in solid formulations
in order to enhance their solubility. They can be used just as well for
direct compression as in sachet formulations or roller compaction.
References
[1] Y. Qiu et.al (ed.), 2009, Academic Press: Developing Solid Oral Dosage
Forms
[2] I. Nikolakakis, J.M. Newton, 1989, J. Pharm. Pharmacol 41: 145 – 148
[3] P.C. Schmidt, K. Benke, 1984, Pharm Ind 46 (2): 193-198
Inhalation Technology
A breath of fresh air in drug delivery!
Dr. Thilo Schmierer,
Business Development Manager
Corinne Malica,
Pharmaceutical Market Specialist
For correspondance: Capsugel France, 10 rue Timken, 68000 Colmar, France – corinne.malica@capsugel.com
Introduction
14 12
New Technologies
[4] J.A. Hersey, 1975, Ordered mixing: a new concept in powder mixing
practise. Powder technol 11: 41-44
[5] European Pharmacopoeia 6, 2012, 7th ed. Council of Europe, Stras
bourg, pp. 2852-2853.
[6] L. Bryan, Y. Rungvejhavuttivittaya, P.J. Stewart, Mixing and demixing
of microdose quantities of sodium salicylate in a direct compression
vehicle, Powder Technology, Volume 22, Issue 2, March–April 1979,
Pages 147-151,
[7] Chee Wai Yip, J.A. Hersey, Perfect powder mixtures, Powder Technolo
gy, Volume 16, Issue 2, March–April 1977, Pages 189-192
[8] Charles C. Yeung, John A. Hersey, Ordered powder mixing of coarse
and fine particulate systems, Powder Technology, Volume 22, Issue 1,
January–February 1979, Pages 127-131
[9] Norman Harnby, An engineering view of pharmaceutical powder mix
ing, Pharmaceutical Science &amp; Technology Today, Volume 3,
Issue 9, 1 September 2000, Pages 303-309
The inhalation route is a fast and effective way of delivering medication locally to the lungs and also for the systemic administration of certain agents. Inhalation
drug therapy is used extensively to treat respiratory conditions such as asthma and Chronic Obstructive Pulmonary Disease (COPD). Recently, it has been
shown that pulmonary drug delivery could also be an effective route to deliver drugs to the systemic circulation thanks to the large surface area of the lungs
with highly vascularised epithelia [1]. Research is ongoing to develop inhalation systems to treat neurological disorders, cystic fibrosis, pain management and
to deliver vaccines.
The Metered Dose Inhaler (MDI) is the original and most widely used device to deliver inhalation therapies. It uses pressurized gas to release its dose when
activated by the patient. More recently, the Dry Powder Inhaler (DPI) has been gaining popularity because it does not rely on propellant to deliver the medication
and patients find it convenient and easy to use [2]. Other systems available on the market include liquid droplet inhalers and nebulisers. When developing
a new product, researchers can select either a standard inhaler device or decide to develop a customized solution that is more tailored to the requirements
of their product and the particular disease area.
Whatever solution is chosen by the company, the effectiveness of the technology will also depend on the ease of use and the patient’s ability to administer
his or her own medication. It is therefore essential that the device is designed using a patient-centered approach. Generally, patients express preference for
devices that are small, portable and easy to use whilst always ensuring that an accurate dose is dispensed. From the company’s point of view, the selected
device must meet stringent manufacturing requirements in terms of its robustness, efficiency and precision whilst remaining environmentally friendly.

Inhalation technology
The burden of chronic respiratory diseases such as asthma and COPD on
patients is significant in both physical and psychological ways. Narrowing
of the airways causes breathlessness which, during an acute attack, can
lead to asphyxia and death if medication is not administered rapidly. Even
normal physical activity can be exhausting, whilst smoke, allergens, or
even expressions of emotion such as laughter or crying can trigger an
asthmatic attack or cause an exacerbation of COPD. Fear of provoking an
acute attack makes patients anxious, forcing them to limit their daily activities
and making them completely reliant on their inhalation product.
“COPD is extremely disabling for me. It’s exhausting not being able to
climb stairs without pausing between each floor.”
Female COPD patient
“Asthma is a disease still considered as “easy to manage”. You just need to
have the proper medication. However, living with it is a constant handicap
for all activities.”
Male asthma patient
Generally, chronic respiratory patients are knowledgeable about their
disease and its treatment; they become experts in juggling between different
inhaler devices for everyday use or crisis management and in adapting
their lifestyles, as well as their medications, to meet the demands of their
illness. Nevertheless, patients often feel embarrassed about appearing
“sick” and being stigmatized in the outside world where such diseases are
poorly understood.2 This means that inhaler systems used to treat respiratory
disease should not only be effective in delivering precise doses, they
should also be small, discreet, easy to carry and easy to use.
Figure 1: Key physical attributes for an inhaler delivery system
Recent market research highlighted various practical aspects mentioned
by patients familiar with inhaler use [2]. The men and women interviewed
were between 20 and 60 years old and were suffering from COPD or
chronic asthma. They had all been using inhalers on a regular basis for at
least a year and had experienced at least two different systems (blister,
capsule or aerosol). When questioned, the patients defined key design
15 13
New Technologies
Inhalers – opening up the airways in respiratory disease
Easy to use
Discreet
PRIMARY
� To avoid additional stress during an acute attack
� Simple treatment implies a less “serious” disease that is
under control
� The device should not attract attention during administration
� Small – it should fit into the palm of the hand
� Unobtrusive style without bright colors to avoid appealing
to children
Portable � Should fit easily into a trouser or jacket pocket
Visible dosing
Easy dose loading
� Remaining doses should be visible to allow the patient
to anticipate when a new prescription will be required
SECONDARY
� Should be possible to load dose into the device quickly
and hygienically
Clean and hygienic � Should be simple to protect and clean the mouthpiece
Separate device
and doses
� To avoid additional costs and wastage
criteria for inhalers as straightforward dose loading, being able to clean
and protect the mouthpiece, and that the device and the dose should be
available separately to avoid wastage (Figure 1).
“A ‘good’ inhalation system for me is a system that is efficient (fast action)
and easy to use, because when a crisis occurs a state of ‘panic’ can set in,
and so there should be no additional stress with a system that is complicated,
and finally it should be correctly dosed and well adapted to the
degree of asthma and the patient’s pathology”
Respiratory Clinician
During the same study, experienced patients were asked to assess the
relative merits of the main inhalation systems currently available: sprays,
blisters and capsules. Sprays have been on the market for a long time and
the metered dose inhaler (MDI) is the reference inhaler device. MDIs are
prescribed mainly for emergency use whilst dry powder inhalers (blisters
or capsules) tend to be preferred for everyday maintenance therapy
(Figure 2).
Figure 2: Comparison of inhalation systems: Patient perception
influenced by device usage
Although sprays are small and simple to use, they do have some drawbacks:
for instance there is no indicator for the number of remaining doses
in the device so that in a life-threatening situation, like an acute asthma
attack, the patient cannot check whether sufficient doses have been delivered.
As sprays can discharge accidentally, the lack of dose counting is
even more worrying. Also the mouthpiece tends to get dusty and requires
scrupulous cleaning. Finally, patients using MDIs need to carefully regulate
their breathing to ensure that the full dose is inhaled.
Blister based inhalation devices are perceived as a more modern approach.
These devices are easy to load and to clean. However, their design
is bigger and bulkier than other inhalers and the devices are more conspicuous
when used in public.
Patients involved in the market research considered capsule-based systems
to be very effective in ensuring precise dose measurement [2]. There
is less wastage compared to blisters because the capsules and the device
are available separately and the capsules are biodegradable and hence
environmental friendly. Loading is considered to be straightforward by the
majority of patients although for some non-users there is a perception
that capsules could be more complicated.

Inhalation technology
Although MDIs are the market leader with 48% of retail sales in Europe
versus 39% for DPIs and only 13% for nebulisers [3], they are gradually
losing their popularity to be replaced by technically superior and more
ecofriendly DPIs.
Dry Powder Inhalers – not only for
respiratory disease
The progress of DPI technology has created opportunities in other therapeutic
areas where systemic exposure is required. Low dosed drugs and
large molecules have been successfully delivered via the respiratory tract
for the treatment of systemic diseases. Potential indications include pulmonary
arterial hypertension, neurological disorders such as Parkinson’s, hereditary
diseases, and pain management including migraines and vaccines.
Inhaled drug therapy is an appealing option for patients because of its
painless and flexible administration compared to injections. Compared to
oral administration, it has the advantage of a more rapid onset of action,
lower dosing, avoidance of first pass metabolism and potentially fewer side
-effects (Figure 3) [1].
� Less drug could be required compared to oral administration
� Onset of action can be more rapid via inhalation compared
to the oral route
� Adverse effects are potentially less severe and less frequent
� Drugs that are not absorbed orally can be delivered via the
lung
� Compared to injectable dosage forms, inhaled drug therapy
is painless and relatively comfortable for the patient which
encourages compliance
Figure 3: Advantages of inhaled drug delivery for treating systemic
disease
One area of interest for DPIs is in inhaled antibiotics for the unmet medical
need of treating cystic fibrosis, a life threatening lung disease and several
studies are ongoing in this indication [4]. In 2010, Novartis gained EU approval
for a dry powder inhaler for tobramycin (TOBI® Podhaler®) [5] and
the FDA granted Orphan Drug Designation for a ciprofloxacin DPI [6].
Another indication for the use of DPIs is for the treatment of viral infections.
Zanamivir® (Relenza®) from GSK is a neuraminidase inhibitor that is
used for the treatment and prevention of influenza. It is formulated as a dry
powder and packaged in four 5mg blisters on a Rotadisk® for inhalation via
the Diskhaler®.
In February 2010, Daiichi Sankyo filed a New Drug Application in Japan for
its influenza drug CS-8958, which is delivered using Hovione’s TwinCaps®
inhaler. Applications are expected soon via Hovione’s licensee Biota for
Europe and the US markets.
16 14
New Technologies
Proprietary DPI technology – how
to stand out from the crowd
To take advantage of opportunities for inhalation drug delivery in both
respiratory and systemic diseases, manufacturers of inhalation drug therapy
are focusing on the development of proprietary technology platforms for
efficient development and manufacturing as well as to differentiate themselves
from the competition.
Strategic decisions are primarily based on:
� Cost efficiency
� Patient acceptability
� Development timelines
� Patent protection of the proprietary solution
“We use a capsule-based system. We were granted a patent for a combination
using HPMC capsules and a capsule-based DPI device”
R&D director, Pharmaceutical Company
The choice of the system can be made at a very early stage before product
development has begun. Input is usually sought from business development
and marketing specialists to ensure that the proposed system is in
line with market trends and will meet customer needs. In early development
stages, R&D works closely with management to look at product performance,
feasibility and timing in addition to the cost of goods and the
position of the new product within the company’s pipeline and product
portfolio. As the project moves ahead studies are required for formulation
development, compatibility and stability, feasibility and scaling up as well
as for the clinical programme.
Figure 4: Development processes for inhalation systems
The overall approach to the choice of technology and the device will depend
on the company’s business strategy. A big pharmaceutical, R&D based
company will prefer to develop or use its own existing proprietary technologies
and will work on formulating the Active Pharmaceutical Ingredient

Inhalation technology
(API) to fit the inhalation drug delivery system. Smaller companies, if not
specialized in inhalation drug therapy, will usually seek outside help from
device manufacturers to find the best available system for their drug
(Figure 4).
The considerations that influence the manufacturer’s decision process
when developing a DPI include dosing, performance, cost efficiency, device
size, number of doses, and functionalities that can offer added value and
product differentiation in terms of patient acceptability e.g. simple to use,
eco-friendly, hygienic and portable (Figure 5).
Figure 5: Criteria for the development of an inhaled delivery system
The most popular DPI technologies are either blister or capsule based.7
Both delivery systems offer comparable performance in high accuracy dosing.
However, blisters rely on more cumbersome, high precision devices for
their administration. The blister devices tend not to be so popular with
patients and seem to be more expensive to produce compared to capsule
systems [2,7]. The advantage of blister based systems may be their suitability
for highly moisture-sensitive products.
When the decision has been made to opt for a capsule-based system, a
capsule supplier is the ideal development partner. A recent market survey
found that Capsugel, the market leader in two piece capsules, was the first
supplier mentioned by respondents [7]. Researchers noted that existing
customers particularly appreciate the development and manufacturing
support provided by Capsugel throughout the development and commercialization
process that ranges from
The choice of the capsule and capsule supplier is as important as the selection
of the inhalation device in terms of the technological suitability, patient
needs, product performance and possibilities for product differentiation
(e.g. device design, capsules branding). Customisation of capsule-based
inhalation systems remains the most effective way of adding value and
making the product stand out from its competitors.
Conclusion
Inhalation technology is used extensively for the local treatment of chronic
respiratory diseases such as asthma and COPD and also in other indications
such as influenza or pain management that require a rapid onset of action
and can be treated systemically via the lungs.
The global market for pulmonary drug delivery is growing rapidly and is
17 15
New Technologies
expected to reach US $37.7 billion within the next five years with the US
and Europe accounting for 75% share. There is a move away from the traditional
MDIs towards newer, more sophisticated DPIs reflecting the increased
research into powder formulations and innovations in particle
engineering. Capsule-based devices in particular, offer many benefits to
patients in terms of precise dosing, ease of use and dose visibility. The
devices are hygienic to use and simple to clean and are presented in attractive
designs.
For manufacturers capsule-based DPI technology provides greater freedom
to innovate and differentiate their products whilst benefiting from
straightforward development, speed to market and efficiency in later manufacturing.
In addition, capsule-based DPIs meet the practical requirements
expressed by patients whilst ensuring effective treatment delivery.
Nowadays, the ideal development partner for capsule systems has to offer
both standardized inhaled delivery solutions for smaller pharmaceutical
and generic companies or more original, tailor-made solutions for larger
companies.
References
[1] Dry Powder Inhalation: Devices, Drugs, Therapeutics, Markets and
Forecasts, Greystone Associates, July 2009
[2] DPI Solutions – Overall landscape and patients’ expectations, Market
Research Study by Vision Critical for Capsugel, April 2011
[3] Lavorini F, Corrigan CJ, Barnes PJ, Dekhuijzen PR, Levy ML, Pedersen S,
Roche N, Vincken W, Crompton GK; on behalf of The Aerosol Drug
Management Improvement Team (ADMIT). Retail sales of inhalation
devices in European countries: So much for a global policy. Respir
Med. 2011 Jul;105(7):1099-1103.
[4] Heijerman H et al. Inhaled medication and inhalation devices for lung
disease in patients with cystic fibrosis: A European consensus J Cyst
Fibros. 2009 Sep;8(5):295-315.
[5] Media Releases: Novartis receives EU approval recommendation for
TOBI® Podhaler®, a fast and simple therapy that helps reduce treatment
burden for cystic fibrosis patients, September 2010 (http://
www.novartis.com/newsroom/media-releases)
[6] Newsroom: FDA Grants Bayer HealthCare Pharmaceuticals Orphan
Drug Designation for Investigational Ciprofloxacin Dry Powder Inhaler
for the Treatment of Cystic Fibrosis, March 2010 (http://
pharma.bayer.com)
[7] DPI Solutions – Overall landscape and clients’ expectations, Market
Research Study by Vision Critical for Capsugel, January 2011
[8] PRWeb. Global pulmonary drug delivery technologies report. March
2010

Agenda
APGI events
Skin and Formulation 4 th Symposium
June 4-5, 2012
2 nd APGI Coating Workshop
April 17, 2013
Lyon Congress Center
Lyon, France
http://www.apgi.org/Skin4.htm
E-mail: apgi.asso@u-psud.fr
Phone: +33-6-29366739 or +33-1-46602510
Fax: +33-1-46835308
University of Lille, Lille, France
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Phone: +33-6-29366739 or +33-1-46602510
Fax: +33-1-46835308
APGI Information days
APGI/ Unipex Information Day: "Controlled
drug and flavour release"
November 20, 2012
CNAM Paris,
Paris, France
APGI/Sanofi Information Day: "Le séchage en
milieu industriel"
April 5, 2013
École Nationale Supérieure des Mines d'Albi-
Carmaux, Campus Jarlard
Albi, France
18 16
Agenda
3 rd Conference on Innovation in Drug Delivery
September 22-25, 2013
Congress Center of Pisa
Pisa, Italy
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E-mail: apgi.asso@u-psud.fr
Phone: +33-6-29366739 or +33-1-46602510
Fax: +33-1-46835308
9 th World Meeting on Pharmaceutics, Biopharmaceutics
and Pharmaceutical Technology
March 31-April 3, 2014
Lisboa Congress Centre,
Lisbon, Portugal
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E-mail: apgi.asso@u-psud.fr
Phone: +33-6-29366739 or +33-1-46602510
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Phone: +33-6-29366739 or +33-1-46602510
Fax: +33-1-46835308

BULLETIN COTISATION A L’APGI 2012/ SUBSCRIPTION FORM TO APGI 2012
MEMBRE ACTIF ET MEMBRE ASSOCIE/ ACTIVE MEMBER AND ASSOCIATE MEMBER
Since July 1, 2010 the French VAT (19,60%) will be added to the amount of the subscription
*(TTC) €
2012 3 Ans/Years
Industrie/Industry ⃝ 165,00 ⃝ 495,00
197,34* 592,02*
Université, Hôpital, Retraité/
Academia, Hospital, Retired ⃝ 70,00 ⃝ 210,00
83,72* 251,16*
Co-inscription APGI + AFEPG
(Association des Enseignants Francophones ⃝ 80,00 ⃝ 240,00
en Pharmacie Galénique) 95,68* 287,04*
Etudiant/Jeune diplômé*, **/ ⃝ 25,00 ⃝ 75,00
Student/Young Graduate*, ** 29,90* 89,70*
*Diplôme de 3 e cycle obtenu depuis moins de 2 ans/ postgraduate diploma since less than 2 years
**Diplôme/Diploma
Ville/Town Année/Year
MEMBRE CORRESPONDANT/
CORRESPONDENT MEMBER ⃝ 200,00 ⃝ 600,00
239,20* 717,60*
MEMBRE BIENFAITEUR/
BENEFACTOR MEMBER ⃝ 500,00 ⃝ 1500,00
À partir de/from 598,00* 1794,00*
⃝ Oui, Oui, je souhaite participer à la journée d’information APGI/Unipex le 5 avril 2013. Journée gratuite pour les membres de l’APGI
Yes, I will participate in the APGI/Unipex Information Day on April 5, 2013. No registration fee for APGI members.
⃝ Oui, je souhaite m’inscrire et régler la cotisation pour 3 ans. J’éviterai ainsi toute augmentation de tarif pendant cette période
Yes, I would like to subscribe and pay for 3 years, this to avoid any increase of the fee during this period.
Nom/Name Prénom/First Name
Institution/Institution
Fonction/Function
Adresse/Address
Tél./Phone E-mail
Adresse de facturation/Invoicing address
MODE DE PAIEMENT/PAID BY
Paiement après réception facture/On receipt invoice:
Chèque ci-joint/Cheque enclosed
Carte bancaire/Credit card
⃝ Visa ⃝ Eurocard ⃝ Mastercard
No carte/Card No
Montant/Amount Expiration/Date of expire
Signature/Cardholderd’s signature
The data may only be used by APGI and its members. According to article 34 of the French Law entitled “Informatique et Liberté“ dated January,
6th, 1978, you have the right to access, modify and delete the data which regard you. To exercise this right or to indicate that the data should
not be used by our members, please write to: APGI at the following address:
APGI • 5, rue Jean-Baptiste-Clément • 92296 Châtenay-Malabry cedex (France), Tél.: +33(0)6 29 36 67 39 or +33(0)1 46 60 25 10 • Fax : +33(0)1 46 83 53 08
E-mail : apgi.asso@u-psud.fr • www.apgi.org, SIRET 434 287 447 00016 • TVA / VAT N° FR 63 434 287 447
19

APGI
5, rue Jean-Baptiste-Clément
92296 Châtenay-Malabry cedex , France
Tél.: +33-6-29366739 or +33-1-46602510
Fax : +33-1-46835308
E-mail : apgi.asso@u-psud.fr
www.apgi.org