AutomatedUV Dissolution Testing

with Fiber Optics

Opt-Diss 410™

2

Overview

• Why Fiber Optics?

• How does it work?

• Cost savings

• Versatility

3

Overview

• What do the regulatory agencies have to say?

• Why the Opt-Diss?

• Who is already using the Opt-Diss?

• Summary

4

Goals for Automation

• Eliminate operator error - better accuracy,reproducibility

• Reduce labor– unattended operation– no manual sampling

• Reduce costs

5

Why UV?

• Much faster than HPLC

• Much cheaper than HPLC– No columns– Less reagents– Less labor

• Now an option even for some multiactiveproducts or single actives with strong excipientinterference!

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Why UV with Fiber Optics?

Because it is easier to move light than liquids!

• Infinite supply of photons• “Spilled” photons don’t cause errors• No carryover• No consumables• Real time data

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Why UV with Fiber Optics?

• Save time– No manual sampling or automated fraction

collection

• Save money– No test tubes, filters, syringes, pump tubing,

cuvettes– Completely unattended operation

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How doesFiber Optic UV

work?

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Schematic

1 Bath1

2

4

3

5

2 UV

3 Fibers

4 Probe

5 Software

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Probe is “In-Situ Cuvette”

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Real Time Spectra

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Near Real Time Dissolution Data

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What about the effects ofexcipients, other

particles, undissolvedcapsules, etc.?

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Uncorrected Profile:

100%

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Light Scattering CorrectionUse algorithms to correct for light scattering producedby turbidity:

• Baseline Correction– Single reference wavelength– Two wavelengths (perpendicular drop)– Average over range

• Derivative– First derivative– Second derivative

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“Average Over Range” BaselineCorrection

0.000

0.050

0.100

0.150

0.200

0.250

0.300

0.350

0.400

0.450

0.500

200 220 240 260 280 300 320 340 360 380 400Wavelength (nm)

Abso

rban

ce

Baseline offset= average absorbance

between and

Net absorbance used tocompute concentrationsand % dissolved

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Corrected Profiles

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How Much Time Can You Save?

• No manual sampling

• No replacing filters

• No flushing/cleaning tube lines

• No replacing tubing

• No calibrating samplers

• No calculating dissolution results

19

How Much Money Can You Save?

For a typical dissolution instrumentrunning:

• 2 tests per day

• 4 time points per test

• 5 days a week

• Analyst’s annual salary of 5M¥

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Savings per Bath

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How Much Money do You Save?

Now how manydissolution baths doyou have in your lab?

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Versatility

Dissolution ofthe fastest

tolongest lastingformulations

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Versatility

Data as rapidly as every 5 seconds

• Ideal for “flash” O. D. dosage forms

• Enables “Time Point Bracketing”– Multiple sample readings around

Time Point– Allows overcoming “anomalous data

points” without having to do stage II

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Versatility

Zero media volume loss

• Unlimited data points– Suitable for any extended release

testing– Complete dissolution profile for

modeling

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Versatility

Dissolution values in real time

• Formulators have opportunity to abortbad tests sooner

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Versatility

No filters, lines, pumps, cuvettes

• No filter clogging• No filter/tubing adsorption or leaching• No algae growth in lines• No problem with hard to pump viscous

solutions• No dirty cuvettes

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What Do Regulatory Agencies Say?

“It’s just another way of performing UV”

USP Chapter <1092>The Dissolution Procedure: Development and ValidationSpectrophotometric Analysis Section:

“Fiber optics as a sampling and determinative method, withproper validation, is an option.”

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What Do Regulatory Agencies Say?

• Several products approved with fiber optics UV asalternative method

• One product released in Europe with fiber optic UVas principle method

• The USP and the multiple FDA locations own anduses an Opt-Diss

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The Opt-Diss 410

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Main Components

• ARCH™ probes• CCD spectrometer

based UV• Deuterium source• Fully integrated

bath(s)• Complete system

software

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ARCH™ Probe

• Available pathlengths: 0.25mm –10.0mm

• Compatible with 400 – 2000 mLmedia volumes

• Versions are available for minivessels (100/200mL)

• Negligible hydrodynamic effect –probes remain resident

• Resistant to bubble formation andparticle trapping

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CCD based UV• Data from all 8 or 12 vessels measured with one

detector

• Simultaneous data collection:

– 8 or 12 channels

– Spectra

• No moving parts

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Detector Image:Signal from all Vessels Projected on CCD

12345678

Wavelength

Vessel

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Deuterium Source

• Low-noise light source

• Precision shutter only moving component insystem– Average life 3.5 million cycles (or 10 years)

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System Software• Defines and controls

collection of UV data

• Synchronizes bathoperation to data collection

• Real-time display ofabsorbance, light intensity,% dissolved andconcentration

• 21 CFR Part 11 compliantwith full audit trail

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System SoftwareMulticomponent capability:

• Can measure products withmore than one API or withsignificant excipientinterference in a single runwithout separation

• Uses well accepted ClassicalLeast Square fittingtechnique

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Why chose theOpt-Diss 410?

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Opt-Diss vs. Competition• Better components:

– Arch™ probes specifically designed for dissolution– Single detector design– Very stable deuterium lamp

• Better software– Complete system control

• One manufacturer for entire system– Better integration– One validation– Full ownership

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Better Components

Exclusive patented arch probe optimizedfor dissolution:

• Available shorter pathlengths (starting at 0.25mm vs.1mm) – able to measure higher concentrations

• Negligible hydrodynamic effect – probes can remainresident

• Resistant to bubble formation and particle trapping

• Can also use dip or microvolume type fiber optic probesfor special cases

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Advantages of the Arch ProbeTransflectance Light Path

Trapped Bubble

Particulate Buildup

Transverse Light Path(ARCH™)

Open structure minimizesbubble entrapment andprevents particulate buildup.

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Better Components (Cont.)

Opt-Diss 2 dimensional scientific CCD detectorsimultaneously captures entire spectrum from all vessels.No moving parts or scanning.

Competitor’s one wavelength at a time detector means:• Have to scan spectrum of each vessel sequentially, so not

truly instantaneous spectrum• Multiplexer to switch among vessels has moving parts,

variability in signal• Need to validate cross-correlation of all channels to

show no channel-to-channel variation caused bymultiplexer

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Better Components (Cont.)

Opt-Diss steady state deuterium lamp has almost novariation as a function of time on the timescale ofdissolution runs.

Competitor’s pulsed xenon lamp has pulse to pulsevariations as high as 50%. Needs continuous compensationwith second reference detector.

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Better Components (Cont.)

Single detector - only one detector to calibrate,validate

• Competitor’s multiple spectrometer design (1per vessel) means:

• “N” detectors to calibrate• “N” detectors to validate each cycle• Validate cross-correlation of all channels to show

no channel-to-channel variation caused bymultiple detectors

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One Manufacturer

Fully integrated solution

• System (bath + analyzer)software

• One validation• Easy changing of volumes,

etc.

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Easy Volume Change

Spacersreproduciblyadjust probeposition

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No Finger PointingOne point of contact for support or to resolve bothbath and analyzer issues.

No …

“It’s the fiber optic system.Call them”

“It’s the bath. Call them”

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Who Uses Fiber Optics?

• Nearly 200 systems installed

• 9 out of top 10 pharma companies

• Non-pharma companies

• The USP and multiple FDA US locations!

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Selected Opt-Diss Users

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Summary

• Fiber optic UV is an accepted dissolutionanalytical method

• Saves time and money• Enables measurements otherwise impossible• Accepted by regulatory agencies

• Opt-Diss 410 is the optimum fiberoptic UV, part of a true completesolution

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Summary

Let us show you what the Opt-Diss 410 can do for you:

• With your samples: We willgladly run them in our lab

• In your lab: Let us demo thesystem for you

Thank You!

Distek, Inc.121 North Center Drive

North Brunswick, NJ 08902Phone (732) 422-7585 • Fax (732) 422-7310info@distekinc.com • www.distekinc.com