Transcript Title

March 2008
Lisapharma – Confidential
1
Company Introduction
&
Proprietary Technologies
March 2008
Lisapharma – Confidential
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LISAPHARMA at a glance
Fully owned by Italian capital
Family-ruled business from its foundation to today
Manufacturing plant of dosage forms in full GMP
compliance, including β-lactam ceph derivatives dedicated
line
Driven to technological developments throughout strong
liaisons with different university bodies
Operative on the Italian and international markets through
a portfolio of proprietary medicines
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Milestones
 1925: Lisapharma is established in Bologna
 1949: HHQQ and plant moved to actual site of Erba (Co)
 1968: first export business to Taiwan
 1970: establishment of international production units in Nicaragua &
Costarica
 1993: first manufacturing activity as toll manufacturer with Novartis
 2000: start of phase-out of production of oral solid non-sterile products
 2002: establishment of the j.-v. with Omicron for the manufacture of
oral solid non-sterile products
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Key facts & figures
 Fully owned Italian manufacturing plant for sterile injection products,
non-sterile liquids, semisolids
 J.-V. participation in Omicron plant (Italy) for oral solid non-sterile
production
 148 total headcounts, out of which 80 reps
 International customers portfolio of 81 accounts
 International sales in 32 different countries worldwide
 Intellectual property of 18 patents covering original technologies
 Development & RA expenditure up to 5.60% of company revenues
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Goals
To consolidate the presence in the Italian market
To improve the penetration in existing countries outside
Italy and to expand to further new markets its business
partneriships
To enlarge the toll manufacturing activities for renowned
international companies
BY………………………..
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Strategy
 In-house development of generic registration dossiers focusing on
niche products (injectable class,…)
 Partnering and/or tightening strategic alliances allowing the best
exploitation of the in-house developed patented technologies
(Sucralfate Gel, Dome Matrix™, Patch-non-Patch™, Chimerical
Agglomerates™)
 Diversification of the product portfolio to include additional non-RX
compounds “dedicated” to specialists (food supplements, medical
devices,…)
 Strengthening the existing collaborations through the proven high
standard of quality and service provided, by doing so attracting new
potential customers too
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PROPRIETARY TECHNOLOGIES
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Proprietary technologies
Long-lasting cooperation between Lisapharma and well
reputable Universities in Italy
Focusing in the development of novel delivery systems,
due to the increased market demand for drug delivery
technology
 Aiming to develop versatility in drug delivery, as much as
adaptability to different drugs to inhance patient
compliance
ALL THIS LED TO
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Proprietary technologies
FOUR PLATFORMS
Dome Matrix™, oral platform
Patch-non-Patch™, transdermal platform
Chimerical Agglomerates™, inhalation nasal platform
Sucralfate Gel, as unti-ulcer for GI tract and skin wounds
The technologies are covered by patents and available for
discussions
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The Platform Concept in DDS
• More than 15% of the total pharma market – in excess of
U$ 80 billion - is covered by drug delivery technolgies
• Future belongs to biotech drugs, to old drugs to be
revaluated, to new drugs offered with appropriate dds, and
to generics
• The systems invented shall posses not only versatility in
delivery, but also adaptability to different drugs
• The term platform indicates a delivery system capable to
be adapted to various drugs, strenghts, mechanisms of
delivery, in order to control not only the time but also the
site of delivery
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DOME MATRIX®
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Dome Matrix®
• The system is based on tablets (modules) with a peculiar
shape made of swellable polymer for controlling the
release rate
• The typical shape of the module is a cylindrical tablet
having one concave and one convex base designed to
allow the convex base to be inserted in the concave
• The shape permits to put together several modules to
create different assembled release systems
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Dome Matrix®
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Dome Matrix®
• A peculiar assembly can be obtained by fitting the concave
base of two modules allowing the construction of a floating
system able to keep the release of the substance into the
stomach
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Dome Matrix®
• Piled configurations can be obtained by staking the
modules convex face into concave face
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Dome Matrix®
• Dome Matrix® finds its ideal application whenever there is
a need for:
a prolonged release of solid dosage forms and it may
represent an effective answer to the need to have
versatility in the substance release kinetics
modulation of dose administered
association of different substances in one modular
system
improving the efficacy of the substance delivered,
providing a time-and-space controlled release system
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Dome Matrix®
• Dome Matrix® technology can be applied
To “old” products presented in innovative dosage forms
New compounds combined with an original and
innovative delivery route
• Dome Matrix® industrial development is in progress
• Dome Matrix® is covered by patent, license or transfer
could be considered
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Patch-non-Patch®
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Patch-non-Patch®
Patches vs. Traditional Systemic Formulations
• Constant plasma levels
• Lower incidence of side effects
vs Injection
vs Oral
Non invasive
Increased bioavailability
More acceptable
Reduced dosing frequency
No need of specialized
No drug interaction
personnel
• Limitation
Low skin permeability (daily dosing < 10 mg)
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Patch-non-Patch®
Patches vs. Traditional Systemic Formulations
• Topical formulations (solutions, creams, gels,…) can:
− Be accidentally removed – contact time
− Applied at the wrong dose
− Stick to cloths
• Patches guarantee control in:
− Dose applied
− Area of application
− Contact time
− Release kinetics
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Patch-non-Patch®
The Typical Structure of a Patch
• Multi-layer structures composed of:
−Backing
−Deposit of the active (solid/liquid)
−(Membrane)
−Adhesive
−Release liner
Backing
Deposit
Membrane
Adhesive
Liner
Minitran®
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Patch-non-Patch®
The Typical Structure of a Patch
Lidoderm®
• Plasters
−Backing (woven-non-woven)
−Thick adhesive hydrogel
containing the active
−Liner
• Gauzes soaked in gel/oil formulations
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Medicell Patch®
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Patch-non-Patch®: the Novelty
Backing
Active+Adhesive
Liner
Patch-non-Patch®
SEM Image
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Patch-non-Patch®: Characteristics
• Dry
• Not self-adhesive
• Flexible, transparent
• Water permeable
• Electrically conductive
• Organic solvents not required
• Adhesive only on wet skin
• Washeable with water
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Patch-non-Patch®
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Patch-non-Patch®: Case Studies
Lidocaine
Estradiol
Hydrocortisone
Caffeine
Nitroglycerin
Herbal extracts
Thiocolchicoside
Progesterone
Rutin derivatives
Ibuprofen lysine
Nicotine&Bupropion
Ketoconazole
Diclofenac
Sumatripan
Clindamycin
Acyclovir
Clorexidine
Nicotinamide&Salicylic ac.
Thyroxine
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Patch-non-Patch®: Production
• Solution (suspension) of all components in water
• Lamination on the release liner at predetermined time
• Oven drying (60-80°C)
• Cutting
• Thickness of 40-200 µm
• Different shapes/patterns possible
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Patch-non-Patch®: The Cosmetic difference
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Patch-non-Patch®: The Cosmetic advantage
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Patch-non-Patch®: Advantages vs
Competitors
Feature
P-n-P®
Patch Plaster Gel
% of active released
High
Low
Low
Low
Time lag
No
Yes
Yes
No
Duration of activity
Long
Long
Long
Short
Adaptation to skin surf.
Yes
No
No
?
Occlusive
No
Yes
Yes/No No
Water soluble
Yes
No
?
Yes
Electrically conductive
Yes
No
?
Yes/No
Cosmetically acceptable
Yes
Yes/No No
Easy to be removed
Yes
No
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?
Yes/No Yes
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Patch-non-Patch®: Advantages vs
Competitors
Feature
P-n-P®
Patch Plaster Gel
Preservatives needed
No
No
Yes
Organic solvents requ.
No
Yes
Yes/No No
Drying step critical
No
Yes
Yes
-
Active crystalliz.critical No
Yes
Yes
Yes
Cost of production
++++ +++
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Yes
++
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Patch-non-Patch
®
Patch-non-Patch® is meant for pharmaceutical, cosmetic,
medical device and medical industries
Patch-non-Patch® feasibility studies with different
actives/prototypes are available and further can be added
Patch-non-Patch ® allows several potential applications
including smoking cessation products, analgesic patches,
caffeine-based cellulite treatments, among the others
Patch-non-Patch ® is covered by patent, license or transfer
can be considered
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Chimerical Agglomerates™
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Chimerical Agglomerates™
• Inhalation nasal platform
• A new nasal form as powder able to satisfy different
technological requirements related to preparation and
administration of powders through non-invasive routes
such as oral, buccal and nasal ones
• The powder is made of agglomerates of micro-particles
obtained by spray-drying process of an aqueous or hydroalcoholic solution containing the substance and excipients
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Chimerical Agglomerates™
• In case of insufflation, the agglomerates dimension are
useful for the dose metering of the powder into the
insufflation device
• After insufflation, due to turbolence of air flow,
agglomerates are broken into fragments of appropriate
dimension for nasal or buccal administration which are
rapidly deaggreagated in the primary micro-particles by
water
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Chimerical Agglomerates™
Primary microparticles
20 µm
 Prepared by spray
drying
 Ø 5-10 µm
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Chimeral Agglomerates
200µm
 Roundish shape
 Free flowing
 Ø 106-850 µm
 They break up into
fragments during
insufflation
Lisapharma – Confidential
Fragments
200µm
 Suitable size for
nasal deposition
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Chimerical Agglomerates™
• Chimerical Agglomerates™ is very versatile system since
it is possible to prepare formulations of different
substances by varying the composition of the microparticles
• Chimerical Agglomerates™ scale of development is
laboratory tested – scale up phase
• Chimerical Agglomerates™ is covered by patent, license
or transfer could be considered
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Chimerical Agglomerates™
• Highly respirable insulin case study
 Dry insulin powders have been prepared by using spray-drying
process starting from suspensions or aqueous solutions of the
active ingredient in acetic acid
 As metering device has been used a commercial device able to
administer 2 mg of insulin powder when activated by an air flow of
60 l/min
 Stability study has been carried out for 12 months during which the
powders have been kept in two different conditions: 25°C-60% RU
and 2-8°C
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Chimerical Agglomerates™
• Highly respirable insulin case study
 Powders obtained form insulin suspensions showed lower values of
FPF (10-30%) compared to those obtained by drying of solutions of
insulin (60-80%)
 Particles obtained applying this latter option have corrugated
surface characteristics, when examined through SEM analysis
 All powders showed a median volume diameter below 5 µm,
therefore suitable for inhalatory administration
 The chemical and physical stabilities of powders obtained starting
from acetic acid solutions were the best one and the hydrolytic
degradation products, the related substances as well as the
covalent aggregation products remain within the spec limits
described in EP, also when the powders were stored at 25°C up to
24 months
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Chimerical Agglomerates™
• Highly respirable insulin case study
 By spray-drying process therefore is possible to obtain dry insulin
powders characterized by high stability and suitable particle shape
able to make the powders highly breathable and manageable for
manufacturing
 These powders show good flow properties which allow them to be
easily charged in a adevice for insufflation
 By this approach insulin crystals are transformed in micro-particles
 The product does not contain excipients, so reducing the potential
side effects associated to them
 The room temperature stability of these pwders allows the product
to be stored in non-refrigerated conditions
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Sucralfate Gel
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Sucralfate Gel
• Sucralfate is a safe and active antiulcer drug
• A new physical form of Sucralfate, named Sucralfate Gel,
has been patented and developed and possesses colloidal
properties due to the reduced particle size
• The material is a humid solid since the drying of the
sucralfate gel causes the lost of the gel properties
• It has been demonstrated that sucralfate gel superior
activity is due to a demonstrated strong bio-adhesion
towards the oral and gastrointestinal mucosa, which allows
the product to persist in contact with the tissue to be
healed
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Sucralfate Gel
• Other than the development of Sucralfate Gel as oral suspension for
the treatment of GI ulcers, the peculiarity of this new material has
suggested a series of further development.
• One of this has been the topical use of Sucralfate Gel for the treatment
of the skin ulcers of various origin, which has got the CE approval as
Medical Device
• This was made possible again by the bio-adhesion properties of the
Sucralfate humid gel that allowed the preparation of a simplified and
self-adherent topical preparation
• The topical preparation can be used also as a carrier for topical
substances and it is patented
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Sucralfate Gel
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Sucralfate Gel
• There are already on the market in many countries various products
based on the Sucralfate Gel technology including:
• Sucralfate gel topical 25% for the treatment of skin ulcers of various
origin (Medical Device)
• Sucralfate gel oral suspension 1g/5ml sachet
• Sucralfate gel oral suspension 2g/10ml sachet
• Dried sucralfate gel tablets 1g (under registration)
• Dried sucralfate gel sequential tablets + ketoprofen
• Dried Sucralfate gel sequential tablets + aspirin
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…Good tips to partnering with Lisapharma
 Small though efficient and dedicated team group allowing quick
decision process
 Flexibility combined to first class service
 Quick adaptation to market changes
 Fast reacting to customers’ demands and needs
 Commitment to innovation
 Very promising tech package portfolio
 Excellent expertise and know how in manufacturing of injection
products
 Independent company not belonging to any group
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