the pharmaceutical composition methodology described in this presentation has been developed to...
TRANSCRIPT
The Pharmaceutical Composition
Methodology described in this presentation has been developed to improve controlled drug delivery through site specific release of marketed or novel pharmaceutical products.
Presentation
•Pharmaceutical composition (PC)
•The Technology
•The Platform
•Therapeutic benefits
•Financial benefits
The Pharmaceutical Composition
Oral pharmaceutical composition• capsulas• other formulations (tablete, suspension etc.)
Controlled drug release• a lot of small particles which are retained and released at targeted place• size of the coated particles is preferably about 20 to about 5000 µm• this results highly reproducible controlled release• better controlled release of drug than existing oral formulations
Site specific drug release • drug is released in targeted segment of GI system (duodenum for levodopa)• this site specific drug release is pH dependent• applicable at diferent segment of GI system (cytostatics etc….)
Technology
• developed technology for the preparation of new PC
• described process for preparing of new oral PC
• technology - fluid bed spray granulation
• it is known technology (modified)
• modification – number and the order of layers over the base
(explanation at next slides)
Figure 1. Spray Granulationhttp://www.glatt.com/cm/en/process-technologies/agglomeration-granulation/spray-granulation.html
Coated particles
Sheme Coated particle
0. drug resin complex
1. controlled release layer
2. bioadhesive layer
3. enteric layer (pH dependent)
diameter 100-5000 µm
The Platform • the technology is usable to different (numerous) drugs
depending on the molecular structure
• 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...
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
Some Other Examples
antipakinsonics antipsyhotics antiepileptics cytostatics other drugslevodopa olanzapineropinirole risperidone
problem uncontrolled administration
uncontrolled administration
uncontrolled administration
uncontrolled administration
uncontrolled administration
result (new formulation – new technology)
therapeutic benefit
√ √ √ √ √
financial benefit √ √ √ √ √
drugs N03 drugs for GI sistem antihypertensives
controlled administration
controlled administration
controlled administration
controlled administration
controlled administration
Inventors and patent applicants
Inventors
•Zdravko Dokuzović•Ljiljana Sović Brkičić
Patent applicants
•Ljiljana Sović Brkičić•Cvjetko Brkičić
Patent Application• the application prepared by patent attorney in Germany
• filed European patent application (EP)• priority date: 6 April 2011
• filed PCT application• international filing date: 5 April 2012• Original document: WO2012136816 (A2) ― 2012-10-11• http://worldwide.espacenet.com/publicationDetails/biblio?
CC=WO&NR=2012136816A2&KC=A2&FT=D&ND=3&date=20121011&DB=EPODOC&locale=en_EP
• filed applications at national phases (at 90 countries)• http://patentscope.wipo.int/search/en/detail.jsf?
docId=WO2012136816&recNum=6&docAn=EP2012056366&queryString=amlodipine&maxRec=4229
Why did we develop a new PC? • to solve problems at treatment of Parkinson disease (PD) • PD is long-lasting disease (life long disease)• PD is characterized by a dopamine deficiency• dopamine is a neurotransmitter in the brain• levodopa (LD) is a dopamine precursor (levodopa dopamine)• it is 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 (30 to 50 years)• duration of LD treatment is 3 to 5 years (existing formulations)• uncontrolled administration of LD causes more side effects • solved problems (with new PC)________________• Duodopa (model drug) – good CR, uncomfortable application
What Did We Expect of a New Drug Formulation?•new (better) forumlation of levodopa•controlled administration of drug (levodopa)•controlled blood level of drug
(it will result with controlled level of levodopa in the brain)•less side effects of drug (levodopa)
•developed technology (The Platform)•which is usable to all molecules containing N (nitrogen) ___________________
problem – uncontrolled administration of drug (blood level of drug is out of therapeutic window – piks)
Dissolution profiles (in vitro)Figure 2. In vitro dissolution profile of
levodopa Figure 3. In vitro dissolution profiles of levodopa
(our pharmaceutical compositions)
Clinical Developement PlanProduce model drug at GMP process
Bioequivalence studies (BE studies)•to compare our PC with existing CR formulations
Clinical trials •small clinical trials•for drugs without comparable CR formulations•the presentation of additional benefits
__________________
similar concept is tested earlier (marketed products)
PCT Patent WO/1998/027961 (DRC + coated particles –dextormetorphane...)
Highlights
Therapeutic benefits• improved safety, efficacy and tolerability• improved compliance
Economical benefits• patent extension• line extension• for payers
Potential Therapeutic Benefits
Competitive advantages of new formulation compared with existing products:
•highly reproducible controlled release•better absorption•controlled drug blood level •lower drug level fluctuations•lower side effects than in existing formulations•lower single dose •lower number of single doses per day•better bioavailability
Economical Benefits• production of better products with competitive advantages
compared to existing drugs
• lower costs of drug tretment (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)
Timetable
• time – the most important factor of this project
(international filing date: 5 April 2012)• duration of patent protection – 20 years• every waste day – lost benefit
R&D (of 10 new formulations)Clinical trials (or BE studies)Location (decision)Laboratory (building)Factory (building)Registration of drugsProduction of drugsMarketing
2014 2015 2016 2017 2018
Drug utilisation - projection
Table 1. Drug utilisation in Croatia, 2012*1. 2. 3. 4. 5. 6. 7. 8. 9.
ATK INN Drug utilisation in Croatia, 2012 (kn),
at 4.500.000 people*
Projection of drug utilisation at 1.000.000.000 people
(kn)**
Projection of drug utilisation at 1.000.000.000 people
(EUR)**
1% 5% 10%1. C10AA05 atorvastatine 113.564.574 25.236.572.000 3.364.876.267 33.648.763 168.243.813 336.487.6272. A02BC02 pantoprazole 94.591.626 21.020.361.333 2.802.714.844 28.027.148 140.135.742 280.271.4843. C09BA03 lisinoprile,
combination80.320.444 17.848.987.556 2.379.865.007 23.798.650 118.993.250 237.986.501
4. C09AA05 ramiprile 62.786.622 13.952.582.667 1.860.344.356 18.603.444 93.017.218 186.034.4365. N05AH03 olansapine 62.577.934 13.906.207.556 1.854.161.007 18.541.610 92.708.050 185.416.1016. C08CA01 amlodipine 61.806.772 13.734.838.222 1.831.311.763 18.313.118 91.565.588 183.131.1767. M01AE01 ibuprofene 58.409.627 12.979.917.111 1.730.655.615 17.306.556 86.532.781 173.065.5618. N05AX08 risperidone 51.635.139 11.474.475.333 1.529.930.044 15.299.300 76.496.502 152.993.0049. C10AA01 simvastatine 50.260.943 11.169.098.444 1.489.213.126 14.892.131 74.460.656 148.921.31310. A02BA02 ranitidine 44.284.427 9.840.983.778 1.312.131.170 13.121.312 65.606.559 131.213.117
Total:**** 201.552.032 1.007.760.160 2.015.520.320Legend:**********
Blue colored - official dana from HALMED (http://www.almp.hr/?ln=hr&w=publikacije&d=promet_lijekova_2012)
Projection of market of the new formulaton, as a part of total market (EUR)***
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)
Projection of drug utilization at 1.000.000.000 citizens as a part of world population (1 EUR=7,5 kn)Drug utilization in Croatia, 2012, http://www.almp.hr/
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 drug price ih higher than projected – new technology, patent protection, better products
Possible cooperation?
Cooperation:
•Business cooperation
•R&D• R&D, protocols, bioequivalence studies, clinical trials etc.
•production
•licensing
•other
