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Delivering
Detail
Diligence
Dedication
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www.jubilantbiosys.com
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The added Dimensionin Drug Discovery
Focus on: DMPK & Toxicology Services
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Proven Expertise in Protein Structure Determination
Permeability
● Caco-2 (A –› B and B –› A); PAMPA; MDCK-MDR-1
Solubility
● Aqueous (various pH); SGF; SIF (kinetic and TD)
Pharmacokinetics
● In Mice (SAM, Nude mice; Balb/c); Rats (S.D, Wistar); Rabbits and Dogs (outsourced)
● Bile duct cannulated rat PK
● Cannulation of portal vein, lymphatic vessel and urinary bladder in rats
● Cassette dosing is possible
● Microsampling in mice
● Dose escalation studies
● DBS (dried blood spot)
Absorption
Metabolic Stability
● Liver microsomes; S-9 fractions and Hepatocytes
CYP and FMO profiling
CYP Induction (PXR/in vivo)
CYP Inhibition
Metabolite ID
● In vitro using liver microsomes, hepatocytes
● In vivo from plasma, bile, urine and feces
Glutathione Trapping
Blood/Plasma Partitioning
Time Dependent Inhibition
Plasma and Chemical Stability
Metabolism
Protein Binding
● Equilibrium dialysis (ED); Ultra filtration
Tissue Distribution
● In Rats (using cold compound)
ED method to determine fu in plasma, tumor, CSF and brain homogenate
Distribution
PK-PD (with in vivo pharmacology)
Toxicokinetics (with Toxicology)
D2M Prediction (with Development group)
Cross Functional Activities
Mass Balance (using metabolic cages)
Biliary and Urinary Excretion
Excretion
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In-Vivo Pharmacokinetics
Mice (C57BL/6, BALB/c, Nude, SCID, SAM) and Rat (Sprague Dawley, Wistar)
Vivo Bio Tech, Hyderabad; Reliance, Mumbai; Harlan and Charles River
Oral, Intravenous, Subcutaneous, Intraperitoneal, Perfusion etc.Capability to cannulate bile duct, portal vein, urinary bladder etc.
Breeding and colony maintained at PalamurBio by Isoquimen, Spain.
Details will be provided on request
Beagle dog (tie-up with PalamurBio, Mahaboobnagar, Hyderabad and Vimta Labs, Hyderabad)
Cynomolgus (Southern Research Institute, USA and Covance, China)
Rodent Dog Monkey
Strains
Routes ofAdministration
Plasma in case of PK studies (in rodents, dog and monkey).In case of rodents we can analyze NCE concentration in all tissues including brain
Matrix for Analysis
Single or Repeated (4/7/14/28-day) dosingRegimen
0.08 or 0.17 (IV only), 0.25, 0.5, 1, 2, 4, 8, 10 (PO only) and 24 hTime Points
5-6 days (PO + IV) 7 days (per route) Will be provided on requestTurnaround Time
20 compounds/week Will be provided on requestCurrent Capacity
Retro-orbital /Tail vein /Jugular Vein (100 µL)
Jugular Vein and Radial Vein (0.5 to 1 mL)Blood Sampling
Animal Source
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Instrumentation and Software
● Six LC-MS/MS instruments (API-6500, API-5500, API-4000: 2; Thermo Ultra and API-4000 Q-Trap with UPLC)● Three HPLC units● Nitrogen evaporators● Refrigerated centrifuges● Deep freezers (-80oC and -20oC)● Freeze-drier● Tissue homogenizer● Franz Diffusion cell● Shaking water bath (Julabo)● CO2 incubator● Genevac evaporator (to remove DMSO)● Microbalances with printer● Positive pressure SPE● Vacuum manifolds with pump● Ultrasonicator● Milli-Q water system● UPS and Standby Generator
● WinNonlin● Graphpad Prism● Galileo LIMS● LightSight software for MetID● Automaton (method development)
● Franz diffusion cells – Skin permeation● RapidFire 365 – For high throughput screening
RapidFire 365 -New Plate Handling
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Turnaround Time for Various DMPK Studies
Study No. Study title Turn around time
1 Solubility in PBS, SGF, FaSSIF, FeSSIF 5-6 days
2 Metabolic stability in microsomes 5-6 days
3 CYP liability 5-6 days
4 Protein binding 5-6 days
5 Caco-2/MDCK-MDR-1/PAMPA assay 6-7 days
6 Stability in plasma/Chemical stability 5-6 days
7 Reactive metabolite study 5-6 days
8 In-vivo PK in rodents 6-7 days
9 Tissue distribution 10 days
10 Biliary excretion 10 days
11 Bioanalytical method validation 15 days
12 Met-ID 15 days
13 CYP profiling 5-6 days
14 Time dependent inhibition 5-6 days
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Throughput of Studies in 2018
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Expertise in Bioanalysis
● Strong bioanalytical team with capabilities to enable fit-for-purpose and/or full validated HPLC and LC-MS/MS methods
● Wide range of in vitro and in vivo assays
● Expertise in handling various matrices (plasma, blood, bile, urine, feces and various tissues)
● Array of sampling processing techniques like precipitation, liquid-liquid extraction, solid-phase extraction and derivatization process
● Enabled highly sensitive methods (pg/mL as LLOQ) for several client programs
● Developed fit-for-purpose bioanalytical methods for various biomarkers using LC-MS/MS and RapidFire (to support efficacy / target engagement studies)
● Chiral separations
● Prodrug analysis
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Preformulation Capabilities
● Intrinsic dissolution in aqueous media
● Dissolution at different pH
● Dissolution in biorelevant media
Dissolution Study
● Bulk density
● Tap density
● Compressibility and Housner ratio
● Flow properties
● Selection and recommendation of preferred excipients for preclinical/ clinical dosage form development
Bulk Properties
● Excipients compatibility study will be preformed with excipients, based on the intended dosage form and formulation development strategy
● Excipients compatibility study will be done by isothermal stress method and will be evaluated for related substance by HPLC analysis
● Based on excipients compatibility, excipients will be selected for further development work
Excipients CompatibilityStudy
● Selection of one lead and one back up for stable salt and polymorph
● Characterization of salt and polymorph
● Stability study
● Solubility study
● PK study in rodents or other species
Salt and Polymorph Screening and Characterization
● pH Solubility profile in buffer system
● Solubility in biorelevant media
● Solubility in presence of solubilizers
Solubility Study
● Crystal shape or habit
● Particle size distribution
● Bulk density and tap density
● Thermal properties
● Powder X-ray diffraction
● Hygroscopicity
Solid State Characterization
● Solution state● Solid state
Stability Study
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Preclinical Formulations Development-Oral Route
Drug/physicochemical/ studypurpose/dose, animal species
Nanosuspension
Solid dispersion
Emulsion, microemulsions, SMEDDS, solid lipid nanoparticles
Discovery/ structural modification
Solution(e.g.: water, pH buffer)
Suspension (e.g: 0.5% methyl cellulose)
Co-solvent and pH Cyclodextrins and pH
Micelles and pH
Micronized suspension
No
No No
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Yes
Yes
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Preclinical Formulations Development-IV Route
Discovery/structural modification
Drug/physicochemical/study purpose/ route, animal species
No
Nanosuspension
Microemulsions, liposomes etc.
pH adjustmentCo-solvent and pH
Cyclodextrins and pHSurfactant and pH
No
Solution (e.g: normal saline, D5W)
No
Yes
YesIn vitro serial dilution
evaluation for precipitation
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Laboratory Animal Facility - Regulatory and Ethical Status
● Jubilant Biosys is committed to the humane treatment of the research animals. Animals are treated with the highest standards of respect, compassion, and particular attention is given to housing conditions, social interaction and enrichment
● The Animal Facility is registered with: “Committee for the Purpose of Control and Supervision of Experiments on Animals” (CPCSEA) Reg. no. 1026/PO/RcBi/S/07/CPCSEA. (Ministry of Environment, Forest and Climate Change, Govt. of India)
● Repeated dose toxicity studies (28 and 90 days) with Functional Observations Battery
● AAALAC full Accreditation since June 2012
● NGCMA certified facility (Jun 2015)
● IAEC (Institutional Animal Ethics Committee) monitors activities related to the animal facility & ensure that all animal experimentation procedures are carried out strictly as per the guidelines and approved study protocols
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Toxicology Capabilities
● Maximum Tolerated Dose (MTD) study
● Dose range finding study (4, 7 and 14 days)
● Repeated dose toxicity studies (28 and 90 days) with Functional Observations Battery
● Toxicokinetics studies
General Toxicology (GLP / Non-GLP)
● Ames test / Mini-Ames study
● Micronucleus test (In-vivo & In-vitro)
● Chromosomal aberration test (In-vitro)
Genotoxicology (GLP / Non-GLP)
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Jubilant Biosys Limited
Bengaluru Research Site:
#96, Industrial Suburb 2nd Stage, Yeshwantpur Bangalore - 560 022 Karnataka India.
Tel: +91 80 66628400
Noida Research Site:
B-34, Sector 58, Noida, Uttar Pradesh 201301
Tel: +91 120 409 3300
For more information:[email protected]
Thank you for your time
