Agilent 8453 Solution Bundles for Spectrophotometer … as fast as a single reading on conventional equipment ... Pharmaceutical Value Chain Informatics Business Strategy ... Survey

Agilent 8453 Spectrophotometer and UV-visible ChemStationfor Dissolution Testing

Solution Bundles for automated Dissolution Testing

General considerations

UV benefits• Simple, rugged and reliable equipment

- lower investment and maintenance costs- lower downtime

• Online measurements and fast results• Ease of operation and faster validation

- less operator time

UV disadvantages• No physical separation of components• Only compounds with a sufficient extinction coefficient can be

analyzed• No direct identification of impurities or decomposition products

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General considerations

LC benefits•Physical separation and identification of entire formulation

- most information about test•Several different detectors applicable

- larger variety of formulations can be analyzed

LC disadvantages•More complex equipment

- less reliable and higher price•More parameter to control •Extra column, solvent and vials required

- higher costs per analysis•Longer analysis time


Agilent Dissolution SolutionUV Analysis

Dissolution Testing Solution based on:• 8453 Spectrophotometer• 3 different sampling systems (automated)• ChemStation for UV-Visible Spectroscopy

Design Goals:• Compatibility• Scalability• Flexibility• Ease-of-learning and Ease-of-use• Regulatory Compliance Tools

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How are samples analyzed?Sampling

Concentration at defined time points for ingredient(s)• On-line monitoring (fiber optics) : no sample transfer

• Manual sampling: sample collection by operator

• Fraction collector: automatic sample drawing and storage

• Off-line sample analysis

• On-line analysis: real-time acquisition, fast analysis required, immediate results


General considerations off-line

Advantages• No direct link to analytical instrument

• Less complexity of setup

• Analytical equipment not tied to dissolution run

• Sample storage with the ability of repetitive analysis

• Allows for longer analysis time even with short sampling times

Disadvantages• Vials for storage required

• Requires non decomposing ingredients

• Results typically available after completion of the run


On-line analysis

Advantages• Immediate results

• Automated runs

• Higher reproducibility, reliability of results

• Frees valuable operator time

Disadvantages• Instrument tied to dissolution tester

• Requires short measurement and analysis time

• Investment cost


On-line sampling with the 8453G1127A Multicell based Sampling (parallel)

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Advantages• Fast cycle time (< 2 min)• No medium loss

(closed loop system)• No cross-contamination• Simultaneous sampling

(compatible with "basket" method)

Disadvantages

• Multiple flow cells• Most expensive sampling system

October 20118453 Dissolution Testing

On-line sampling with the 8453G1128A Valve based Sampling (sequential)

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Advantages

• Single cell• Reliable• Less expensive

Disadvantages

• Longer cycle times between time points(5, 7.5 or 10 min cycle)

• Medium loss (to waste)• Potential sample carryover• Vessel-to-vessel delay

(may be incompatible with "basket" method)


On-line sampling with the 8453 - G1129A Multi-Apparatus Valve Sampling (sequential, parallel)

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Advantages

• Single cell• Reliable• Lowest cost per apparatus


Disadvantages• Longer intervals between time pts. (5, 7.5 or 10 min cycle)• Lost medium• Potential sample carryover• Vessel-to-vessel delay (may be incompatible with

"basket" method)

Agilent UV-Visible Spectroscopy SystemsThe 8453 Spectrophotometer

Agilent 8453 UV-Vis Spectrophotometer- 190-1100nm Wavelength Range- 1nm Slit Width, 1nm Sampling Interval- 0.1 second Full Spectrum Scan- Fully EP & USP compliant

-> improved Resolution, lower Stray Light- Instrument logbooks

-> GLP

Key advantage: spectral information by defaultAcquisition as fast as a single reading on conventional equipment


Spectrophotometer Instrument Design

Detector

SampleLight

source

Polychromator

Entrance slit

Dispersion element

Monochromator

Sample

Detector

Light source

Entrance slit

Exit slit

Dispersion element

Conventional single-beam Spectrophotometer

Diode Array Spectrophotometer


UV-Visible ChemStation Software Product Structure

Biochemical Analysis

Add-on product

General PurposeBase product

AdvancedAdd-on product

Standard Execute Advanced Verification and Diagnostics

AdvancedDissolution TestingMultibath Dissolution Testing

Kinetics

ThermalDenaturationCombined Report

DissolutionAdd-on product

Security PackAdd-on product

Security PackAdd-on product


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Dissolution Testing ModeMain Screen


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Agilent 8453 Dissolution TestingBath Driver Concept

Agilent ChemStation Bath “Driver”

RS2

32

LAN

, G

PIB

Agilent 8453Spectrophotometer

Sample transfer

Datatransfer

DDE Connection DDE Connection


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Agilent Apparatus DriverG7900AA

•Dissolution Apparatus Control

− Via Dissolution method− Direct Control Dialog

•Online Monitoring and Check of apparatus parameter

− Variable Data Reading Frequency•Data Integration into a single results file

•Supported Apparatus Models:

− Agilent 708-DS/709-DS− VK 7025− VK 7000/7010


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Dissolution Testing Mode Single Component Quantification

Standard• Unlimited number of standards• Choice of four calibration curve types• Single, average or three-point background

correctionAdvanced• Any combinations of wavelengths• Any spectral processing (e.g. derivative + smooth)• Least squares or Maximum Likelihood fit• Single or multi-wavelength values


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Can eliminate the need for chromatographic separation

Dissolution Testing Mode Multi-component Quantification

Advanced (only)

• Unlimited number of standard spectra• Any spectral processing (e.g. derivative)• Calibration with pure component standards or with mixed

component standards• Least squares or Maximum Likelihood fit• Graphical and statistical evaluation tools

• standard deviation for each analyte• the standard deviation of calibration


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Agilent UV-visible ChemStationDissolution Software Summary

•Rich Data Analysis features•Full Spectral Acquisition support •Match Factor for Sample Integrity checking•Multi-ingredient Formulation Analysis•Excipient Corrections

•On-line Control and Monitoring• Open System Architecture via apparatus driver

• Flexibility and Scalability• Sampling System independent Method

• Security Pack Software for 21 CFR Part 11 compliance


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8453 Systems OverviewDissolution Features

Off-line Sampling

Multicell Sampling

Valve Sampling

Multibath Sampling

Apparatus Driver G7900AA applicable

No Yes Yes Yes, individual per apparatus

Minimum Cycle Time

Any > ~1 minute, free adjustable

5, 7.5 and 10 minutes

5, 7.5 and 10 minutes

Volume loss/measurement

3 - 10 ml none 3 - 7 ml 3 - 7 ml

DosageDropping

Any Simultaneous Staggered Staggered


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8453 Systems Ordering Product Numbers

Off-line Sampling

Multicell Sampling

Valve Sampling

Multibath Sampling

8453 with PC, Printer and Base Software

G1815A G1815A G1815A G1815A

DissolutionSoftware

G1118AA G1118AA G1118AA G1118AA

Apparatus Driver

NA G7900AA G7900AA G7900AA

Sampling System

None or89090A SipperG1811AAutosampler

G1127A G1128A G1129A(2 apparatus),G1130A(adds apparatus)

Apparatus NA 708-DS 708-DS 2 708-DS,+ additional


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Where selling Agilent Dissolution Equipment?Pharmaceutical Value Chain

Informatics

BusinessStrategy

DiseaseUnderstanding

TargetIdentification

TargetValidation

Lead CompoundSelection

Generate Compound

Evaluate Compound

Optimize Compound

Discovery Testing

Process Research& Scale UP

Stability &Formulation

Safety Testing

Exploratory DrugCandidate (EDC)

Investigational New Drug

(IND)

Phase I Trials

Phase II Trials

Phase III Trials

New DrugApplication (NDA)

Manufacturing

Post MarketSurvey

Phase IV Trials

Bioavailability

Disease Discovery

DrugDiscovery

DrugDevelopment

ClinicalTrials

Manufacturing & Post MarketSurveillance


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Agilent 8453 Dissolution Testing System (R&D)

Features/Benefits Single apparatus, automated on-line UV dissolution testing system

Acquisition of complete spectra for flexible re-evaluation of result during method development

Flexible reports and vessel grouping (e.g. 3/3) Meets all USP/EP specifications and 21 CFR part 11 (electronic

records and signatures)

Control and monitoring of dissolution baths of all major manufacturers

System configuration 8453 Pharmaceutical System G1815AA

Dissolution Software G1118AA

Apparatus Driver Software G7900AA

Fast Sampling system G1127A

708-DS Dissolution apparatusProcess Research

& Scale UP

EDC

IND

Safety Testing


DrugDevelopment

Stability &FormulationStability &

FormulationNew bundled system: G7922AResearch 8453 Dissolution System


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Agilent 8453 Dissolution Testing System (QA)

Features/Benefits Single and Multi Apparatus dissolution testing (maximum 4)

Less expensive compared to parallel sampling

No cell difference compensation required

Flexible reports and vessel grouping (e.g. 3/3) Meets all USP/EP specifications and 21 CFR part 11 (electronic

records and signatures)

Control and monitoring of dissolution baths of all major manufacturers

System configuration 8453 Pharmaceutical System G1815AA

Dissolution Software G1118AA

Apparatus Driver Software G7900AA(per apparatus)

Valve based sampling ( >= 5 minutes)

G1128A (single) orG1129A (dual) + G1130A (additional one)

708-DS Dissolution apparatus (up to 4)Process Research& Scale UP

EDC

IND

Safety Testing

DrugDevelopment


New bundled systems: G7920A, G7921AValue 8453 Dissolution SystemMulti-apparatus 8453 Dissolution System


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Options available withBundled 8453 Dissolution Systems

Option #890 Delete Printer• Customers apply networked printers

Option #695 Delete PC• Customers have their preferred PC/IT equipment vendor

Option #900 System without 708-DS apparatus• Customers require a specially configured apparatus• Customers want to automate existing equipment

Option #910 Replace 708-DS with 709-DS apparatus• Customer wants bathless apparatus


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Agilent 8453 Dissolution Testing SystemsSummary

Easy ordering structure of online 8453 Dissolution Systems

Sampling according to needs suitable for pharmaceutical formulation development as well as quality control

New brochure availablePN 5990-7389EN


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Documents

Agilent 8453 Solution Bundles for Spectrophotometer … as fast as a single reading on conventional equipment ... Pharmaceutical Value Chain Informatics Business Strategy ... Survey