Transcript Oral pharmaceutical composition - BLC pharmaceutica

The Pharmaceutical Composition
Methodology described in this presentation has been developed to improve
controlled drug delivery through site specific release of drug.
Described technology is usable to marketed or novel pharmaceutical products.
Croatia, Zagreb, June 10, 2015
Ljiljana Sović Brkičić
Presentation
• new formulation of drug - Pharmaceutical composition (PC)
• The Technology
• The Platform
• Therapeutic benefits
• Financial benefits
The Pharmaceutical Composition
Oral pharmaceutical composition
• capsules (particles placed in capsules)
• other formulations (tablets, suspension etc.)
Controlled drug release
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a lot of small particles which will be placed in capsules
drug is released during the time (from PC)
size of the coated particle is preferably about 20 to 5000 µm
this results with highly reproducible controlled release
it is better controlled release of drug compared to existing oral formulations
Site specific drug release
• a lot of small particles which are retained and released at targeted place
• this site specific drug release is pH dependent
• release of drug is possible at diferent segment of GI system
(for levodopa targeted place is duodenum)
The Technology
• it was developed the technology (our own technology)
• it was described process of preparation of new PC
• the technology is fluid bad spray granulation (modified)
• modification:
• number od coatings
• the order of coatings
• www.glatt.com
Coated particle
3. enteric layer (pH dependent)
2. bioadhesive layer
1. controlled release layer
0. drug resin complex
diameter 100-500 µm
The Platform
• the technology is usable to different (numerous) drugs
depending on the molecular structure
• it is usable to all molecules containing N (nitrogen)
• the technology is suitable for active agents belonging to
Class I of the Biopharmaceutics Classification System (BCS)
which are characterized with high permeability and high
solubility
• preferred group of drugs - antiparkinsonics, antiepileptics,
antipsychotics, antihypertensives, cytostatics etc...
_____
• EU project
• timetable
• R&D - levodopa
2016
I
1
2
3
4
5
6
II
2017
III
IV
I
II
2018
III
IV
I
II
III
R&D (characterisation of complex)
R&D (optimatization of PC of levodopa)
Production in GMP process
Bioaviliability studies
Project management
Publication of project
6 month
method
12 month
R&D
duration of project
6 month
BE studies
12 month
registration
IV
2019
I
The Potential
The potential of the technology – it is applicable to:
• all innovative drugs
• innovative drugs at the end of patent protection
(to prolong the patent protection)
• generic drugs (for preparation of the generic drugs with an additional value)
Finalized formulations:
•
•
•
•
•
levodopa + carbidopa or benzerazide and entacapone
ropinirole
antipakinsonics
antipsyhotics
risperidone
drugs
levodopa
olanzapine
ropinirole
risperidone
olanzapine
problem
uncontrolled
uncontrolled
administration
administration
result
controlled
controlled
alendronate
antiepileptics
N03
cytostatics
other drugs
drugs for GI sistem antihypertensives
(new formulation
– new technology)
administration
administration
uncontrolled
administration
controlled
administration
uncontrolled
administration
controlled
administration
uncontrolled
administration
controlled
administration
therapeutic
benefit
financial benefit
√
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√
√
√
√
√
√
√
√
Patent application
Patent application
• the application prepared by patent
attorney from Germany
• filed European patent application
(EP)
• priority date: 6 April 2011
• filed PCT application
• international filing date:
5 April 2012
• Original document:
WO2012136816 (A2) ― published
2012-10-11
• filed applications at national
phases (at 90 countries)
• „search report” of October 17, 2013
•
http://worldwide.espacenet.com/publicationD
etails/biblio?CC=WO&NR=2012136816A2&KC=
A2&FT=D&ND=3&date=20121011&DB=EPODO
C&locale=en_EP
Inventors and applicants
Inventors
• Zdravko Dokuzović
• Ljiljana Sović Brkičić
Patent applicants
• Ljiljana Sović Brkičić
• Cvjetko Brkičić
Why and What?
• to solve problems at treatment of
Parkinson disease (PD)
• PD is long-lasting disease (end life)
• dopamine deficiency causes PD
• dopamine is a neurotransmitter (brain)
• levodopa (LD) is a dopamine precursor
• the drug of choice in the treatment of PD
(“gold standard”)
• it is the most effective drug in the
treatment of PD
• duration of PD is 30 to 50 years
• duration of good LD treatment is 3 to 5
years (with existing formulations)
• uncontrolled administration of LD causes
more side effects
• drug treatment – low and slow
• the idea was to prepared oral
formulation of levodopa with good CR
• we were solved problems of
uncontrolled administration of
levodopa (with new PC)
•
•
•
•
•
•
•
•
•
•
•
•
•
•
it was developed new PC
it is PC with controlled administration of drug
it is controlled release of drug
it is site specific release of drug
it enables controlled blood levels of drug
it causes less side effects of drug (levodopa)
it was developed the new technology
it is The Platform
it is usable to all molecules containing
nitrogen (N)
the technology will be presented at the
example of levodopa
levodopa is used as a model drug
technology will enable great therapeutic
benefit to persons with PD
potential financial benefits will be bigger on
the other examples
it is technology for blockbusters
(past and future)
Dissolution profiles (in vitro)
Figure 2. In vitro dissolution profile
(of existing formulation of levodopa)
Figure 3. In vitro dissolution profiles
(of our profiles of levodopa)
Competing solutions (levodopa)
grade
description
5
too good
4
excelent
3
2
A
Technological
complexity
B
Innovativeness
C
Therapeutical benefit
1
acceptable
0
bad
D
E
F
G
Side effects
Availabilility for
patients
Simplicity for use
Price
Highlights
Therapeutic benefits
• improved safety,
efficacy and tolerability
• improved compliance
Economical benefits
• patent extension
• line extension
• for payers
Trials (plan)
• Bioavailability study
• Bioequivalence study
• Small clinical trials
Trials (note)
• known main substance
• known additional
substances
• NO - big clinical trials
Concept – tested earlier
• WO/1998/027961
• TRL – technology readiness level
Benefits
Therapeutic benefits
• it is highly reproducible
controlled release
• it enables better absorption
and better bioavailability
• it enables controlled blood
levels of drug
• it enables lower fluctuations
of blood levels of drug
• it causes lower side effects
• it will be applied lower
single dose
• it will be applied lower
number of single doses a day
Economical benefits
• production of better products
with competitive advantages
compared to existing formulations
• lower costs of drug treatment
(duration of PD – 50 years)
• higher price of drug - compared to
the price of existing drugs – (new
position – use, features, price)
• broadly acceptable technology
(The Platform)
• higher costs of production – new
technology (compensation at
higher price, better products,
market ratio)
Drug utilisation - projection
Table 1. Drug utilisation in Croatia, 2012*
1.
2.
3.
4.
ATK
INN
Drug utilisation in
Croatia, 2012 (kn),
at 4.500.000
people*
5.
6.
Projection of drug utilisation
at 1.000.000.000 people
(kn)**
Projection of drug utilisation
at 1.000.000.000 people
(EUR)**
7.
1%
1.
C 10AA05
atorvastatine
113.564.574
2.
A02BC 02
pantoprazole
94.591.626
3.
C 09BA03
80.320.444
4.
C 09AA05
lisinoprile,
combination
ramiprile
5.
N05AH03
olansapine
62.577.934
6.
C 08C A01
amlodipine
61.806.772
7.
M01AE01
ibuprofene
58.409.627
8.
N05AX08
risperidone
51.635.139
9.
C 10AA01
simvastatine
50.260.943
10.
A02BA02
ranitidine
44.284.427
Total:****
Legend:
*
**
***
****
62.786.622
25.236.572.000
21.020.361.333
17.848.987.556
13.952.582.667
13.906.207.556
13.734.838.222
12.979.917.111
11.474.475.333
11.169.098.444
9.840.983.778
3.364.876.267
2.802.714.844
2.379.865.007
1.860.344.356
1.854.161.007
1.831.311.763
1.730.655.615
1.529.930.044
1.489.213.126
1.312.131.170
8.
9.
Projection of market of the new formulaton, as a
part of total market (EUR)***
5%
33.648.763 168.243.813
28.027.148 140.135.742
23.798.650 118.993.250
18.603.444
93.017.218
18.541.610
92.708.050
18.313.118
91.565.588
17.306.556
86.532.781
15.299.300
76.496.502
14.892.131
74.460.656
13.121.312
65.606.559
201.552.032 1.007.760.160
Drug utilization in Croatia, 2012, http://www.almp.hr/
Projection of drug utilization at 1.000.000.000 citizens as a part of world population (1 EUR=7,5 kn)
Projection of market of new drug (our PC) as a part of total market (new technology, patent protection, better products)
Corection factor (higher drug price - patent protection, factor 2 or 3)
Blue colored - official data from HALMED (http://www.almp.hr/?ln=hr&w=publikacije&d=promet_lijekova_2012)
10%
336.487.627
280.271.484
237.986.501
186.034.436
185.416.101
183.131.176
173.065.561
152.993.004
148.921.313
131.213.117
2.015.520.320
Market potential
• market potential is bigger than presented at Table 1.
• targeted population is bigger than projected at Table 1.
• market of EU (Croatia is member of EU)
• market of Asia and Africa region
• other markets – USA, Canada, Japan
(not included in projection)
• potential price of drug is higher than what is projected –
it is the new technology, patent protection, better products
• usable to different drugs (blockbusters – past and future)
• Market potential of new formulation of levodopa (project):
Year
1.
2.
3.
4.
5.
Share of market (%)
2
4
6
8
10
Number of DDDs
Number of capsules
8,760,000
26,280,000
17,520,000
52,560,000
26,280,000
78,840,000
35,040,000
105,120,000
43,800,000
131,400,000
Legend: 1 EURO = 7,6 HRK; DDD for levodopa + carbidopa 0,6 g
Revenue (EURO)
18,603,474
37,206,947
55,810,421
74,413,894
93,017,368
Possible cooperation?
Pharmaceutical company or Investor
• R&D of new formulations (fast development of new products)
• Trials – Bioavailability studies or small clinical trials
• Production
• Licensing
________________
• Project
• Steps
Project
Development
Proceeding 1
Proceeding 2
Registration
Production in
GMP proces
Trials
Proceeding 3
Proceeding 4
Proceeding 5 and Proceeding 6
Future
Commercialization
The Opportunity…
Patient
• better drug treatment (better therapy)
Pharmaceutical company
• business opportunity
Investor
• investment to project with global potential
Innovator
• to find way for finalization of project
Contact
• http://www.pharmaceutica.blc.hr/
• Ljiljana Sović Brkičić
• [email protected]