Zyleris PharmaTech specializes in innovative high-throughput experimentation technology for applications in topical pharmaceutical and personal care product industries. We provide high-throughput screening services for topical formulation development. Services provided: 1. High-throughput Franz Cell skin absorption and penetration screening service. 2. High-throughput screening of compound library to identify candidates for topical and transdermal delivery. 3. High-throughput absorption depth profiling in stratum corneum layer. 4. Skin absorption and penetration enhancement development service. 5. Topical formulation development and optimization service. For more information about the technology and our services, please visit us at www.zyleris.com.

1. High-Throughput Franz Cell Technology
Platform For Topical Formulation Screening
Best of Both Worlds – Speed and
Efficiency (High Throughput ) and Data
Compatibility (Standard Franz Cell)
Zyleris PharmaTech (Lake Bluff, Illinois, U.S.A)
1

2. Topical Formulation Development –
Challenges and Opportunities
• Industry standard Franz Cell technology (static and flow-
through type) – low throughput and expensive.
• No HTS technology in the market for topical formulation
or compound library screening.
• Limited number of formulations screened in topical
formulation development process. Question: is the
formulation slated for clinical development really best
possible one to move forward?
• Small number of compounds evaluated for topical and
transdermal delivery.
2

3. Zyleris’ High-Throughput Screening (HTS)
Technology – Design Considerations
• Compatibility with the standard Franz Cell (not re-
inventing the wheel).
• Multiple screening modes (absorption and penetration).
• Galenic forms (semi-solids/liquids and transdermal
patches).
• Contact between tissue and receptor medium.
• Efficient mixing.
• Precision temperature control.
• Sample collection (fast, easy, and automation-ready).
• Last, but not least – high-throughput.
3

4. Zyleris’ HTS Technology – Design Features
• Franz Cell principle – static type with a donor and
receptor chamber separated by a tissue membrane.
• Each HTS station is a compact, modular 108-cell unit
(size: 12x11 inches).
• Diffusion area 0.5 sq. cm (8mm is in diameter.) in each
HTS cell.
• All glass and Teflon construction (chemically inert).
4

5. Zyleris’ HTS Technology – Key Design
Advantages
• Key factors in ensuring data reliability and reproducibility
(from system design point of view): mixing, sampling,
and temperature control.
• Unique design that eliminates potential stagnant layer or
bubbles between tissue membrane and receptor
medium.
• Efficient mixing without vortexing.
• Sampling mechanism to ensure uniformity in sample
collection across all HTS cells in the screening station.
• Precision temperature control.
5

6. Zyleris’ HTS Schematic and Workflow
Load Screen Collect
= Individual Cell
Analysis
6

7. Zyleris’ HTS Technology – Operating
Features
• Same operating principle as Franz Cell – process,
collect, and analyze.
• One tissue membrane for each cell in HTS station.
• Parallel processing.
• Fast and easy sample collection.
• Controlled and efficient mixing.
• Controlled temperature.
• Fully validated against standard Franz Cell (We provide
free technology comparison and validation service).
7

8. Zyleris’ HTS Technology – Screening
Features
• Applicable to all common dosage forms – gels, lotions,
creams, ointments, serums, solutions, etc.
• Applicable to transdermal patches (matrix- and reservoir-
type). Adaptable for iontophoretic patch.
• Flexible enough for any type of skin absorption and
penetration study.
• Animal and human skin tissues as well as synthetic
membranes.
• Ocular, buccal, lung, or any other tissues, nails (with
adapter).
• Finite and infinite dose (occlusive or non-occlusive).
8

9. Zyleris’ HTS Technology – Screening
Features: The Case of Transdermal Patches
• Membrane/matrix type – cut the patches into circles and
carry out HTS screening as same as semi-solid/liquid
dosage forms.
• Reservoir type
Current system: accept reservoir diameter up to 8mm
(Min. diameter: 12 mm including peripheral seal).
Modified system: accept reservoir diameter up to 11mm
(Min. diameter: 15 mm including peripheral seal).
9

10. Zyleris’ HTS Technology - Key Benefits
• Franz Cell in a high-throughput fashion.
• First HTS technology capable of operating at absorption
and penetration mode.
• Speed and efficiency (lower cost per formulation).
• Data compatibility with standard Franz Cell.
10

11. Services Provided
• High-Throughput Skin Absorption and Permeation
Screening
• High-Throughput Screening of Compound Library for
Topical and Transdermal Delivery
• High-Throughput Absorption Depth Profiling in Stratum
Corneum Layer
• Percutaneous Absorption and Permeation Enhancement
Development Services
• Formulation Development and Optimization Services
11

12. Skin Absorption and Penetration Screening
Services
• Penetration Mode
API collected in receptor medium.
• Absorption Mode
API absorbed in epidermis and/or dermis layer.
• Absorption and Penetration Mode
API absorbed in epidermis and/or dermis and collected
in receptor medium.
• Absorption and Penetration Mode - Mass Balance Study
API left on skin surface, absorbed in stratum corneum
(SC) layer and epidermis and/or dermis layer, and
collected in receptor medium.
• Custom Mode
Any type of absorption and penetration study.
12

13. Skin Absorption Depth Profiling in SC Layer
• HTS Formulation Screening
- Absorption and release in SC layer.
• High-Speed Tape-Strip Processing
- Capable of processing 48 tape strips at a time.
- Consistency and uniformity across all strips during
each stripping cycle.
- Strip pooling for depth profiling.
- Solvent extraction/digestion.
13

14. Formulation Screening - Schematics
Topical
Absorption
Transdermal
Penetration
14

15. In Vitro Absorption and Penetration
Screening Services – Skin Model
• Fresh Pig Ear Skin
- Standard model
• Human Cadaver Skin
- Standard model
• Custom
- Customer may request or provide tissue membranes for
specialized studies.
15

16. In Vitro Absorption and Penetration
Screening Services – Skin Integrity Test
• Measurement of Electrical Resistance (Impedance)
- LCR meter operated at 100 – 1,000 Hz (lower frequency generally
yields greater sensitivity and better differentiation) .
• Electrical Resistance (Impedance, Z Value)
- Dependent upon skin type, temperature, frequency, testing
medium, etc.
• Established Threshold Value in Our Laboratory
- Fresh pig ear skin => 5 Kohms at 100 Hz.
16

17. In Vitro Absorption and Penetration
Screening Services – Sample Processing
• Stratum Corneum (SC) Layer
Tape-stripping followed by solvent extraction.
• Epidermis and/or Dermis Layer
Tissue digestion/homogenization followed by solvent
extraction. Separation of epidermis from dermis.
• Receptor Medium
- Saline, PBS or TBS buffer
- Saline, PBS or TBS buffer with a non-ionic surfactant
(e.g., oleth-20) or BSA for hydrophobic API.
17

18. In Vitro Absorption and Penetration
Screening Services – Data and Reporting
• Data
Raw data as total amounts at each data point.
• Reporting
Project report including detailed protocol, experimental
procedure, and data.
18

19. In Vitro Absorption and Penetration
Screening Services – Analytical Services
• Standard method of analysis
LC-MS-MS.
• Method development/transfer
- Develop new method.
- Method transfer.
• DIY (Do-It-Yourself) Analysis Option
Samples are returned to customers for their own
analysis.
19

20. Study Protocol
• Screening Protocol
Three replicates per formulation (N=3).
Rapid formulation screening and lead generation.
• Optimization Protocol
Six replicates per formulation (N=6).
Formulation fine-tuning and optimization.
• Custom Protocol
Per specification (N= any number).
20

21. HTS – Current Capability
• Penetration Study (Transdermal)
70 formulations per week (three replicates and 3-4 data
points per formulation).
• Absorption and/or Penetration Study (Topical)
35 formulations per week (three replicates and 3-4 data
points per formulation).
• Zyleris has the capacity (2,200 HTS cells) to equip 20
HTS stations – screening capability can be easily
ramped up, when needed.
21

22. Business Model
• HTS Screening Service – Fee-for-Service
- Clients supply formulations* to be screened. Pricing is
quoted based on per formulation.
- Formulations developed by Zyleris.
*: Zyleris offers preformulation and formulation development services.
22

23. Turnaround Time
Typical Guideline – In Transdermal Mode
• Up to 70 formulations (three replicates per formulation).
• Up to 4 data points at 2, 4, 8, and 24 hr.
• Timeline*
- Formulation screening + DIY analysis option: within 2-3
weeks.
- Formulation screening + LC-MS-MS analysis +
reporting: within 4-5 weeks.
* Actual turnaround time is typically sooner than the above guideline.
23

24. Pricing
Factors that affect the pricing:
• Study mode (transdermal, topical absorption, depth
profiling, mass balance, etc.).
• Replicates per formulation.
• Data points.
• Number of formulations.
• Number of APIs in each formulation (if analytical service
is selected).
• Any special handling requirements.
24

25. Thank you!
25