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.

1
The Pharmaceutical CompositionMethodology
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 Sovic Brkicic

2
Presentation

• new formulation of drug - Pharmaceutical
  composition (PC)
• The Technology
• The Platform
• Therapeutic benefits
• Financial benefits

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The Pharmaceutical Composition

• Oral pharmaceutical composition
• capsules (particles placed in capsules)
• other formulations (tablets, suspension etc.)
• Controlled drug release
• 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)

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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

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Coated particle
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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
• RD - levodopa

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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
• risperidone
• olanzapine
• alendronate

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Patent application

• Patent application

• Inventors and applicants

• 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/publicationDetails/
  biblio?CCWONR2012136816A2KCA2FTDND3date
  20121011DBEPODOClocaleen_EP

• Inventors
• Zdravko Dokuzovic
• Ljiljana Sovic Brkicic
• Patent applicants
• Ljiljana Sovic Brkicic
• Cvjetko Brkicic

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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)

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Dissolution profiles (in vitro)

• Figure 3. In vitro dissolution profiles
• (of our profiles of levodopa)

• Figure 2. In vitro dissolution profile
• (of existing formulation of levodopa)

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Competing solutions (levodopa)
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Highlights

• Therapeutic benefits
• improved safety, efficacy and tolerability
• improved compliance
• Trials (plan)
• Bioavailability study
• Bioequivalence study
• Small clinical trials
• Concept tested earlier
• WO/1998/027961

• Economical benefits
• patent extension
• line extension
• for payers
• Trials (note)
• known main substance
• known additional substances
• NO - big clinical trials
• TRL technology readiness level

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Benefits

• Therapeutic benefits

• Economical 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

• 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)

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Drug utilisation - projection
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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)

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Possible cooperation?

• Pharmaceutical company or Investor
• RD of new formulations (fast development of new
  products)
• Trials Bioavailability studies or small
  clinical trials
• Production
• Licensing
• ________________
• Project
• Steps

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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

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Contact

• http//www.pharmaceutica.blc.hr/
• Ljiljana Sovic Brkicic
• ljiljana.sovic_at_gmail.com