Z-Dis MUXMulti-Channel Dissolution Monitor
Software Specification & Manual(Revision 0.9)

Process & Sensors Dept.:

Dr. Konrad Mack.................

.................................

Project Manager:

Jens Mondry.................

.................................

Quality Manager:

Reinhard Sallen.................

.................................

© 96-98 by Carl Zeiss Jena GmbH, OEM/M2 Sensors and Process Analytics Div.Document
created:Last update:

18/12/1996
26/05/1998

byJ. Mondryby

J. Mondry

Contents

1.

Hardware and software system specification

4

2.

Installation and File Structure6

2.1 Installation

6

2.2 Directories, Files and Access rights

6

3.

General system design10

4.

Automatic Dissolution Testing

12

5.

6.

7.

8.

4.1 The Main Screen

12

4.2 The Dissolution Run

14

4.3 The Run Info Dialog

18

4.4 Inter-Channel Calibration

19

4.5 System Suitability Test

21

4.6 Calculations used in Dissolution run

22

4.8 Dissolution Run Report25

Manual Operation of the System

26

5.1 The Manual Screen

26

5.2 Edit Sample Point Table

29

5.3 Calculations used in Manual Module

30

5.4 Z-Dis MUX parameter file format

31

Technical setup

32

6.1 The setup screen

32

6.2 Passwords

34

Validation

35

7.1 The Validation screen

35

7.2 Description of VK7000 test routines

37

7.3 Description of GP700 test routines

39

7.4 Description of MCS 500 series test routines

40

Project History

43

Supplements

44

Algorithm for smoothing and derivatives according to Savitzky-Golay

46

Labview Graph Handles

48

Zeiss ASPECT plus data file format

50

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1.

Hardware and software system specification

The Z-Dis MUX Dissolution Monitor Software will be designed and compiled using exclusively
National Instruments LabView development system (current release 4.01). The software is
to be programmed under and designed for MS Windows NT 4.0. The software will not be
portable (without recompilation) to other operating systems.
Being a Win NT 4.0 application, the Z-Dis MUX Dissolution Monitor Software will require thefollowing minimum hardware and software environment:•

IBM compatible Pentium (150 MHz or better recommended) with at least 32 MB RAM (64MB recommended)•

2 serial interfaces plus (!) mouse port•

about 50 MB of free capacity on an NTFS formatted (to enable file security features of NT)
harddisk (100 MB+ recommended)•

SVGA graphics card

•

Mouse

•

MS Windows NT 4.0 (logged on to a NT network)•

NT graphics mode set to 1024 x 768 x 256 colors, small fonts (!)•

A suitable printer (Laserjet type) and a suitable storage device (harddisk) must be logged on
to the network for remote protocol printout and data storage. The machine running Z-Dis
MUX must have access to the network printer and storage device.

Maximum raw data storage (every measured spectrum, parameters, results) for a 20point run will typically require about 500-700kByte. This could sum up to a typicalmonthly total ( 2-6 runs /day, 7 days / week) of approximately 30-50 Mbyte. Thus astandard 1-2 Gbyte harddisk will be sufficient for at least a 1-2 years of data storage.
• No Eco-PC (Power savings etc.) settings installed or activated (*)

Because Z-DIS MUX is designed for long duration runs it is strongly recommended touninstall or disable, respectively, any Eco-PC settings of your PC ( the likes of e.g.
processor shut-down if no input is made by mouse or keyboard etc.)• The MCS spectrometer, the VanKel Dissolution Bath and the DiCon GP700 multiplexer must
be properly connected to their respective interface ports of the PC

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2.

Installation and File Structure

2.1

Installation

In order to enable the PC to communicate with the MCS spectrometer unit via the plug-in PC
card the device driver for the spectrometer (kernel mode driver ) must be properly installed on
the system. The MCS 500 kernel mode driver is delivered on a separate disk together with thecomplete system.
The Z-Dis MUX software will be delivered on 3.5” disks complete with a standard installation
routine. To start the installation:• insert disk 1 into the floppy drive of your PC• run ZDISMXnn.EXE to install the software (nn.. release number)
The software will now be installed, the required directories etc. will be automatically created.
If an older release of the software is already installed on your system the old INI file settings will
be read and reused in the new installation. A registry group will be created holding the required
icons.

2.2

Directories, Files and Access rights

The installation must be carried out having Administrator access rights in NT. The software
can be installed into any directory. This directory will contain subdirectories for parameter files,
local data files and routine check (validation) protocols.
The access to these files (and also to the applications INI file) can be limited using the log-in
security features of NT/Z-DIS MUX (see below).

In order to employ the log-in routine of NT as the primary user determination and to make useof the built-in security mechanisms of NT ZEISS suggests to have the Z-Dis MUX software
installed and maintained by an (Administrator level) IT person and operated by the (User level)

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ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

lab personnel. The rights to delete or even modify acquired raw data and to manipulate vital ZDis system data will be restricted to Administrator level.
In any case the PC running Z-Dis MUX must have access to the network printer and data
storage, if required.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

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2.3

Data files

The measured spectra will be stored in the ZEISS native ASPECT plus data file format

For a description of the ZEISS ASPECT plus data file format see Supplement D..
All results of a runfor every sample point:•Time, sample and standard reading,•% Diss of vessels 1-6,•

Min Diss Result•

Max Diss Result•

Mean Diss Result•

Temperature (°C) , flag according USP ( specified temperature +/- 0.5°C)•

Stirring rate (rpm) , flag according USP ( specified rpm +/- 4%)

together with additional information (including an optional text descriptor field)•

Batch No.

•

Raw File Names••

Product
Compound••Stability Y/NStabiltiy Conditions

•
•
•
•
•

Strength
Media
Media Volume
Basket/Paddle
Method Name

•
•
•
•
•

Time Points
Condition
performed byAnalystApproved bywill be stored in form of a result ASCII file which can be used and edited e.g. in MS Excel. In
addition a printed protocol (according to ) can be generated on any active system printer.The
required additional information (that is not part of the applied method file but describes theindividual run) will be prompted for (dialog box) at the beginning of a run.

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3.

General system design

The following diagram shows the arrangement of components in the complete Z-DIS MUXsystem.

10

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software SpecificationZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

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4.

Automatic Dissolution Testing

4.1

The Main Screen

This screen displays the essential data during the dissolution run.
On the right side (top) the status of the devices and essential method selections are indicated.
The buttons on the right side open up secondary screens like On-line help, Manual Mode,
Technical Set-up and Device Check & Validation.
The controls of this screen (submenu buttons, graph selectors) will be individually enabled or
disabled according to the access level of the currently logged-in operator. (See 4.1 accessrights)
The filename and path of the current parameter file are displayed in the Headline Bar of thiswindow. Two graphs (dissolution curves and spectra display) represent the measured data.
For a description of the graph manipulation handles (left of the graphs) see Supplement C.

12

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

Short description of main screen controls and indicators:

Dissolution Graphdisplays the dissolution curves for any single or all of the dissolution
vessels. The vessels to be displayed can be specified in the
checkbox array left of the dissolution graph.

Spectradisplays the spectra for any single or all of the dissolution vessels.
The vessels to be displayed can be specified in the checkbox array
left of the dissolution graph (to avoid overloading the graph maybe
this should be restricted to radio button type, i.e. spectra of one
vessel at a time)

Energy/Absorbance/2nd Deriv: This switch can be used to toggle
between the display of the raw energy spectra, the backgroundcorrected absorbance spectra and their second derivs.

Single / All sample points: This switch can be used to toggle
between the display of the last measured spectrum of a vessel andan overlay of the spectra of all measuring points, i.e. theconcentration series

Timeshows the current duration of the dissolution run [hh:mm:ss].
This counter is started at the first sample reading of the run

Sample Point
F1 Run / Stop

indicates the current sample point
After a confirmation prompt the dissolution run will be started, F2-F5
buttons will be disabled. Pressing this button again will stop the
dissolution run. (All data produced by then will be stored)

F2 Load Paras
F3 Manual Mode
F4 Setup
F5 Validation

Load a method file (parameters) produced in Manual Mode
Manual Measurement and Parameter Set-up
Technical set-up (COM Port settings, Passwords etc.)
Collection of routine checks to confirm functionality of : Multiplexer,
Bath, Spectrometer, Data Evaluation Module (and maybe Probes).
Validation reports will be generated, printed and stored.

F10 Quit

After a confirmation prompt the Z-Dis MUX software will be ended.

All displays are continuously updated while the dissolution run is performed.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

13

4.2

The Dissolution Run

The Automatic Dissolution run (F1 Run) follows a defined routine which is described in thefollowing table.
Step

Dialog Box

Description

1

Initialisation of MUX (COM, Time), Spectrometer (Port,
Integration time, averaging) and Bath (COM).

2

Run Info Dialog Box

The program prompts for additional information describing
the run.

3...8

Insert Tablet / Basket Nr.

In a specified interval (currently depending on the MUX[1..6][OK]settling time) the operator is prompted to insert tablets /baskets. The time of confirmation is recorded as the zerotime point for the run of the corresponding vessel.

9..n

For every sample point:at SP – 20 seconds blank andstandard measurement is repeated.Then read 6 sample
spectra and the current temperature and rpm data from thebath. The concentration (%Diss) is determined from thecurrent blank/standard calibration and displayed in the
dissolution graphn+1

Run completed[OK]Store all acquired data, (local or remote), print protocol,
indicate the completion of the run.

The whole sequence can now be repeated with the next
method.

14

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15

16

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software SpecificationZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

17

4.3

The Run Info Dialog

This section will be completed, when the assignment of all parameters to either method orindividual run is clarified. (J.M.)

18

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

4.4Inter-Channel Calibration

The immersion probes have different transmission curves. In order to compensate for thesetransmission differences energy measurements are taken from all channels and are used tocalibrate the raw energy measurements in the channels.
The smallest automatically adjusted integration time is determined from all channels.

E1...8 (λ )Bubble detection:

If the determined integration time is too high or if it takes the system toolong to determine the integration time a bubble is assumed to be in the respective probe.
A warning message is issued and you may repeat the ICC after you have cleared therespective channel. If the determined ICC factor exceeds a given value (as specified in
the Run Info dialog) the same assumption is made by the program.
Using the determined common integration time (in order to avoid saturation in any of thechannels) energy measurements are taken from all channels at the same measuringconditions.
The channel N that yields the highest output value (counts) is selected as reference for theother channels. The ratio ("ICC factor", which in fact is a function of the wavelength, not a factor
as such) is computed for every channels as

ICC1...8 (λ ) =E N (λ )E1...8 (λ )Of course ICCN = 1 for all λ.

Example set of ICC curves:
These ICC curves are multiplied to every new energy measurement

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification19

measuredE1used(λ )..8 (λ ) = ICC1...8 (λ ) ⋅ E1...8in order to compensate for the transmission differences. So, being normalised to one energy
level, the energy spectra are now used to compute the absorbance spectra from sample andreference channel etc.

Spectrum graph

The upper left graph displays the energy spectra that are takenfrom the 8 channels

ICC graph

Below this the computed ICC factor curves will be displayed.

Test

After the ICC is completed you can run a test measurent on all 8
channels to see the accuracy of the ICC correction.

Test spectrum graph

The corrected spectra will be displayed in the right side graph. The
spectra should now be sufficiently congruent.

Repeat ICC

If required (bubbles), the ICC can be repeated.

Continue Run

Confirm ICC and continue

20

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

4.5

System Suitability Test

The System Suitability test is performed before the run.

The user is prompted to fill Vessel 8 with Standard 1. Then a blank and Standard
reading is taken.
Now the user is prompted to fill Vessel 8 with Standard 2. A Standard reading is taken,
the ratio of both standard readings is computed and the difference of the ratio and100% is compared to the Maximum allowed difference as specified in the Run Info
dialog. The SST is flagged accordingly.
A series of 6 readings is now taken from vessel 8. The %RSD is computed andcompared to the Maximum allowed %RSD as specified in the Run Info dialog. The SST
is flagged accordingly.
For the calculations used in SST see chapter 4.5.

The results of the SST are stored in the Dissolution Result file (4.5) and added to the
Dissolution report (4.6). The measured standard spectra (energy raw data) are stored inspectra files and can be viewed etc. with the Aspect+ software.
The results of the system suitability test are displayed in a message box. Upon
confirmation the dissolution run continues.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

21

4.6

Calculations used in Dissolution run

Spectra are measured in counts (diode), representing the energy input I(λi) onto the diodearray.
The wavelengths λi represented by the diodes are computed during the initialisation of thedevice from non-linear coefficients. These coefficients are provided by the manufacturer andstored in the MCS spectrometer’s internal EEPROM in the course of calibration and system
integration of the device. Because of the spherical characteristics of the spectral imaging these
λi are non-equidistant values, they differ slightly from an exact equidistant series of wavelength
values. In the course of the computation of absorbance spectra and values derived from them(concentrations etc.) the λi are recomputed to an array of equidistant λi values.

Blank & Background
Spectrum

E Blank ,Bckgr (λi ) = I Current (λi ) − I Dark (λi )Standard & Sample
Spectrum :E Std , Sample (λi ) = I Current (λi ) − I Dark (λi )Absorbance Spectrum : E S tan dard , Backgrnd (λi )

Abs S tan dard , Backgrnd (λi ) = − log
Blank
(
)
E
λ
i


 E Sample (λ ) 
Abs Sample (λi ) = − log Background i (λi )E( )Abs Std , Sample λ i = linInterpolation(Abs(λi ))2nd Deriv of Absorbance:( )SGsmoothSGderiv

Standard & Sample
Reading
resp.

22

(

(

Der Std , Sample λ i = SGderiv SGsmooth Abs Std , Sample))

numerical smoothing operation according to
Savitzky-Golay (see Appendix of Z-Dis Software
Manual)numerical 2nd derivative operation according to
Savitzky-Golay (see Appendix of Z-Dis Software
Manual)Rd Std ,Sample = Abs Std , Samplet (λevaluation )Der Std ,Sample = Abs Std , Samplet (λevaluation )ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

The spectral value at the fractional index of λevaluation is computedby linear interpolation.

Standard Response:

Re s Std 1, 2 =Rd Std 1, 2
Conc Std 1, 2

resp.

Re s Std 1, 2 =Der Std 1, 2
Conc Std 1, 2

Std Ratio 2 & Ratio 1

Re s Std 1
Ratio =
× 100
Re s1Std 2

Pass/failRatio → <>100 ± NomRatio%RSD Std2%Dissolution?

2
σ (Rd 2Std,..., 7 )% RSD =× 100
2
µ (Rd 2Std,..., 7 )withσ (x ) =andµ (x ) =% Diss Sample =1 n−1(xi − µ (x ))2∑
n − 1 i =0
1
n

n −1

∑x
i =0

i

Rd Sample Volume
×× 100
Re s Std 1 Dosage

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

23

4.7

Dissolution Run Result & Data Files

Excerpt from example data log file:....... Raw data stored in : M:\ARCHIVE\ZDIS_MUX\DATA96\S0105V00.R01 etc ;M:\ARCHIVE\ZDIS_MUX \DATA96\B0105BCK.R01 ;M:\ARCHIVE\ZDIS_MUX \DATA96\R0105STD.R01
Standard Concentration = 1,20000 mg/ml
Nominal Volume = 500 ml
Formulation = 500
Calibration Wavelength = 400,00 nm
Background Absorbencies....
Corrected Sample OD....
RESULTS....

The results of a run will be stored in plain ASCII files. These files can be re-printed, viewed, or
imported into Excel, Word etc. any time.

24

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

4.8

Dissolution Run Report

Each Method will produce a separate report. In any case an ASCII data file is created, if AutoPrint is enabled in the Technical Setup menu, the report will be printed after the run on thecurrently selected system printer. The printer must be pre-selected before the use of thesystem.
The page header includes :•Method, ARD reference number, Operator, Date & Time of the run•

Location and name of all data files(standard, blank & sample spectra, ICC data, SST spectra )•Location and name of parameter files

The footer includes:•

Version, page n of m

The report data include:•

Standard concentrations•

System suitability responses, RSD of System suitability•

Standard responses, response of last standard, ratio of standards•

Table of dissolution results, for every sample point:time, Mean, Min, Max, bath temperature, rpm & USP flagfor every sample vessel:
result, rpm, vessel temperature & USP flag•Individual vessel plots (like in the robotic software) including Q, Q+5, Qtime marker•

Mean Min Max plot (like in the robotic software) including Q, Q+5, Qtime marker•

Additional information to describe the run (see 2.3 )The layout of the report sheets will be designed as close as possible to the reports produced by
the Zeiss / Zymark Robotic Dissolution System.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

25

5.

Manual Operation of the System

5.1

The Manual Screen

The Manual Module is used to create and evaluate parameter files for the automateddissolution runs. It allows you to observe the complete spectra and their 2nd derivatives in order
to find the best calibration wavelength, integration time and other settings for the special
analytical problem.
The filename and path of the current parameter file are displayed in the Headline Bar of thiswindow.

For a description of the graph manipulation handles (upper right of the graphs) see
Supplement C.

26

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

Short description of Manual screen controls and indicators

Integration time

Integration time of the MCS 500 diode array spectrometer.

Average

Number of spectra to be averaged by the spectrometer in eachmeasurement.

MethodSample Points

Icon switch paddles / baskets
Number of sample points (measurements)
Edit : Calls a dialog box, that allows the operator to define thesample points. The sample point table (Nr, Time) can be filledautomatically ( Immediate release, Controlled release ) withpredefined segments corresponding to a total time and thenumber of sample points, or, respectively, can be edited
manually.

Standard Conc.

Specifies the concentration of the standard that will be measured(F5 Standard) and that will be used for the automatic run. The
value is required to compute the concentration of a sample
measurement.

Dosage Size

Specifies the dosage size that is required to compute theconcentration (%Diss) of a sample measurement.

Vessel Volume

Specifies the vessel volume that is required to compute theconcentration (%Diss) of a sample measurement.

Data Source

Icon switch to toggle between usage of Absorbance spectra or
2nd deriv of Abs.

Calibration
wavelength

Specifies the wavelength at which to compute the calibration
curve. The current calibration wavelength is indicated by a redline cursor in the graphs.

Smoothing

Determines the number of measuring points included in thesmoothing algorithm for the computation of the 2nd derivative.

F1 Help
F2 Load Para
F3 Save Para

On-line help
Load a method (parameter set)
Save a method (parameter set). File dialog box will be displayedin any case (thus works as both Save/Save as)

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

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F4 Save SpectraStores the currently displayed spectra in ASPECT+ file format.

Sample, Blank,
Standard[Shift F1 F6]Blank measurement. The obtained spectrum will be stored asblank (reference) for manual standard and sample
measurements.Standard measurement. The obtained spectrum
will be stored as Standard for evaluation of manual sample
measurements.
Sample measurement. The obtained spectra are blank(reference-) corrected. If a valid standard has been measured, ora MCA model is employed, the concentration(s) is(are) computedand displayed.

F5 ICC Run

Performs the inter-channel calibration to update the correction
factors for the differences of the individual channels

F7 Plot
F10 Quit
Spectra2nd Deriv

28

Plot current spectra and deriv graphs.
Quit Manual Module.
Displays measured spectra
Displays 2nd derivative of standard and sample spectra

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

5.2

Edit Sample Point Table

This dialog can be used to define and edit the series of samplepoints for the dissolution run.
The table is presented as a graph and on the right sight of the dialog box.
Use the two buttons to create two different types of sample point series.
Immediate Release: n sample points are created with the specified interval

example: SP 3 Interval 5 ->5, 10, 15 min

Controlled Release: n+m sample points are created with the specified intervals

example: SP 4 4 Interval 5 10 -> 5,10,15, 20,30,40,50,60 min
In addition the time table can now be manually edited.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

29

5.3

Calculations used in Manual Module

Spectra are measured in counts (diode), representing the energy input I(λi) onto the diodearray.
The wavelengths λi represented by the diodes are computed during the initialisation of thedevice from non-linear coefficients. These coefficients are provided by the manufacturer andstored in the MCS spectrometer’s internal EEPROM in the course of calibration and system
integration of the device. Because of the spherical characteristics of the spectral imaging these
λi are non-equidistant values, they differ slightly from an exact equidistant series of wavelength
values. In the course of the computation of absorbance spectra and values derived from them(concentrations etc.) the λi are recomputed to an array of equidistant λi values.

Blank Spectrum :E Blank (λi ) = I Current (λi ) − I Dark (λi )Standard & Sample
Spectrum :E Std , Sample (λi ) = I Current (λi ) − I Dark (λi )Absorbance Spectrum : E Std , Sample (λi )

Abs Std , Sample (λi ) = − logBlank(λi )  E

( )Abs Std , Sample λ i = linInterpolation(Abs(λi ))

( )

(

(

))

nd
2 Deriv of Absorbance:

Der Std , Sample λ i = SGderiv SGsmooth Abs Std , Sample

SGsmoothnumerical smoothing operation according to Savitzky-Golay(see Appendix of Z-Dis Software Manual)ndnumerical 2 derivative operation according to Savitzky-Golay(see Appendix of Z-Dis Software Manual)

SGderiv

Standard & Sample
Reading

Rd Std ,Sample = Abs Std , Samplet (λevaluation )resp.

Der Std ,Sample = Abs Std , Samplet (λevaluation )The spectral value at the fractional index of λevaluation is computed by linear interpolation.

Concentration:

30

Conc Sample =Rd Sample
× Conc Std
Std
Rd

Conc Sample =Der Sample
× Conc Std
Std
Der

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

5.4

Z-Dis MUX parameter file format

A parameter file contains all necessary parameters for a complete dissolution run. The
parameter files are stored in plain ASCII (use notepad or any other ASCII viewer)Example:[GENERAL]
FileID=Z-Dis MUX Dissolution Monitor Parameter File
Time=21.11.1995/12:26:49
Origin= Z-Dis MUX Dissolution Monitor V n.nn
Note=[Spectrometer]
IntegrationTime=25
Accumulation=20[Method]
Method=0
SamplePoints=3
SampleTimes=10;110;210
StdConc=1.0003
DosageSize=500
VesselVolume=300
MaxBackgroundAbs=0.0002
CalibWavelength= 400.00...
[Evaluation]
UseDeriv=0
Smooth=8CalibWavelength= 400.00[MCA]..(special settings for MCA modelling & evaluation)

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

31

6.

Technical setup

6.1

The setup screen

The Technical setup screen includes controls for several software settings.

Directories

Validation Data

Report files produced in the Validation submenu

ICC Data

Inter-channel correction data

Manual Data

data files generated in the manual mode

Parameter Files

Parameter sets (Methods) for dissolution runs

Multivariate Models

Multivariate model and calibration files referred to from multivariate(not used in this release)methods (parameter sets)

32

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

Spectral Raw Data

All raw spectra produced during a dissolution run

Dissolution Results

Storage of the Dissolution Reports on a network PC or, respectively, in a
local backup directory, if the network path is not accessible

Settings
Store dissolution results

Generate result file of the run (basis for report)

Store spectral raw data

Store all raw spectra produced during a dissolution run

Auto-Print

Print Dissolution Report automatically at the end of each Dissolution run.

Emulation

Enables Device emulation of Bath, MUX or spectrometer for off-line
demonstration purposes

Probes present

In case of any of the sample probes missing, the probe can be disabled
here, the system will still be able to perform runs.

COM Ports

GP 700, VK 7000

COM port settings for MUX and VanKel BathZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

33

6.2

Passwords

In this dialog, the password list can be modified along with the assigned access rights.
To add a new password enter the name and the password and assign an access level.
To remove a password from the list delete both name and password and the corresponding line
will be removed.
Z-Dis MUX access level hierarchy:
level

access to0

Administrator

everything

1

Chief operator

everything, except technical parameters(no access to Technical Parameter Setup)2

Operator

Load predefined methods and monitor automatic
measurement only34

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

7.

Validation

7.1

The Validation screen

The Validation screen gives access to special check and validation routines to create regular
reports on the status of hard- and software.

Most of the individual test routines (except for some required basic tests) can be
included/excluded by checking/unchecking the corresponding checkboxes. The test routines
will be performed in the given order. Test routines that run for a more than a few seconds will
display their own progress window, displaying essential information, temperature curves,
spectra etc. The test series can be cancelled any time.
Two types of reports can be created. The standard report lists date & time, device, test
identification and completion for every individual device test. This protocol is displayed on-line
to follow-up the progress. This report can be stored and printed.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

35

An extended protocol holds additional information, especially for the MCS spectrometer device,
like durations, limits, actual values, measured spectra etc. For the first release of Z-Dis MUX
this extended information is for storage and evaluation by Zeiss only. It will be made open andprintable as soon as possible.
The created validation reports can be printed and / or stored in a special validation directory.
This directory can be specified in the Technical Setup menu.

36

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

7.2

Description of VK7000 test routines

Communication: Initialisation
The serial communication with the VK 7000 unit is initialised according to the COM port settings
specified in the Technical Setup menu. A number of test commands is sent andacknowledgement is checked.

Communication: Synchronise Date & Time
The serial communication with the VK 7000 unit is once more checked by downloading thePC’s current date and time to be set on the VK7000, and afterwards verifying it, thus
synchronising the internal clocks of both the devices.

Mechanics: Drive Unit Lift/Lower
The drive unit of the VK 7000 is automatically moved down, up and down again in order toensure the proper function of drive and limiting switches.

Mechanics: Shaft Drives
The paddle spin velocity is sequentially set to 50, 100, 150 and 200 rpm and the actual rpm
value is read and displayed.

Mechanics: Sample Manifold Lift/Lower
The sample manifold is automatically moved down, up and down again in order to ensure theproper function of the manifold drive.

Temperature: Confirm Bath & Vessel Temperature(*)
The current temperatures of bath and sample vessels as send by the VK7000 are displayed.
They can be checked with an external temperature. Any required VK7000 calibrations of thethermosensors could / should be performed now. The current temperature readings must be
confirmed by pressing the OK button.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

37

Temperature: Thermostatting(*)
The nominal bath temperature is set to 36°C. The temperatures of bath and sample vessels as
read by the VK7000 are displayed in a temperature–time graph. The test routine finishes when
the bath temperature reading is 36°C. This test can take a couple of minutes, depending on theinitial bath temperature. If the thermostatting of the VK7000 pump unit works properly, a linear
increase of all temperatures can be observed.
(*) Please note that due to technical reasons (VanKel) the vessel thermistors will start sending
temperature data only from about 30°C and above.

38

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

7.3

Description of GP700 test routines

Communication: Initialisation
The serial communication with the GP 700 unit is initialised according to the COM port settings
specified in the Technical Setup menu. A number of test commands is sent andacknowledgement is checked.

Communication: Synchronise Date & Time
The serial communication with the GP 700 multiplexer unit is once more checked bydownloading the PC’s current date and time to be set on the GP700, and afterwards verifying it,thus synchronising the internal clocks of both the devices.

Mechanics: Positioning
The multiplexer is moved into all 8 positions and the signal is checked to ensure proper
positioning of the fiber switch.

Optics:Energy throughput (*)

The multiplexer is moved into all 8 positions and the signal is measured without multiplexer andwith the multiplexer inserted in the optical path.
(*) This test requires optical fibres to be rearranged at the spectrometer in order to measure theenergy throughput without multiplexer.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

39

7.4

Description of MCS 500 series test routines

The device test and validation routines implemented in this section are a direct implementationof parts of the Zeiss PA 224210-7121.000 internal Quality Test instruction as applied in the
production facility.
Some of the validation routines require only the measuring beam to be covered-up (darkcurrent etc.), some require special filters (and therefore a simple cell holder and two fibres).
These filters must be available to perform the corresponding tests.
NaNO2 solution cell for false light
test, cell holder and monofibres.

Filter-Set (HELLMA 666.000)
with Holmiumoxide & Standard
filters for wavelength andphotometric validation

Communication:40

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

Initialisation
The communication with the MCS 500 series spectrometer via the PC interface card isinitialised. The firmware is downloaded and a number of test commands is sent andacknowledgement is checked.Mechanics:

Shutter operationThe shutter isopened and closed several times and the energy throughput is monitored.

Spectrometry:

Energy and Sensitivity

The test routine automatically determines an optimum integration time for all the following tests(approx. 85% of the dynamic range). The resulting energy curve is displayed and evaluatedaccording to factory specifications.

Spectrometry:

Dark current test

Amount and uniformity (peak-to-peak noise and overall values) of the dark current signal of thespectrometer are checked according to factory specifications. The measuring beam must becovered (insert filter into cell holder turned by 90°) for this measurement. The dark current
signal is displayed.

Spectrometry:

Baseline reproducibility

The reproducibility of the spectral baseline in the range from 215 – 620 nm is determined.
After a reference measurement 10 sample measurements are performed and displayed, andthe baseline stability is checked according to factory specifications.

Spectrometry:

Baseline noise

The noise of the spectral baseline at 250 nm is determined.
After a reference measurement 50 sample measurements are performed and displayed, andthe measurement value at 250 nm is displayed in a graph. Finally the results (peek-to-peek) arechecked according to factory specifications.
Attention! It takes this test about 20 s to complete. Cell holder and optical fibres must not be
moved during the test!

Spectrometry:Zero-transmission noise

The zero-transmission noise at 250 nm is determined. On request the measuring beam must becovered (insert filter into cell holder turned by 90°) for this measurement.
After a reference measurement 50 sample measurements are performed and displayed, andthe measurement value at 250 nm is displayed in a graph. Finally the results (mean value,
standard deviation) are checked according to factory specifications.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

41

Attention! It takes this test about 20 s to complete. Cell holder and optical fibres must not be
moved during the test!

Spectrometry:

False light component

The false light component at 240 and 340 nm will be determined using NaNO 2 solution.
After a reference measurement a measurement of the NaNO2 solution will be performed.
The resulting spectrum will be displayed and the false light component is evaluated according
to factory specifications.

Spectrometry:

Wavelength accuracy & reproducibility

The wavelength accuracy is determined using a Holmiumoxide filter.
The wavelength accuracy is checked 10 times at 4 different wavelengths with the peek position
being determined by a 20-point interpolation between the spectral points. The resulting
spectrum is displayed and the wavelength accuracy is evaluated according to factory
specifications.
The wavelength reproducibility is checked as the largest wavelength difference between thesemeasurements and can be further investigated by long-time comparison of the validation
results.

Spectrometry:

Photometric accuracy

The photometric accuracy is checked using a standard filter set (Pm10) with defined reference
values. After a reference measurement the standard filters are measured and the measured
absorbancies are evaluated according to factory specifications and the defined values of thestandard filters.

42

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

8.

Project History

Release 1.0

First delivery release

due : xx.06.98

Release 0.9

Release According to User Interface Design Review P.Rogers’ visit to Jenareleased: 05.05.98- clear graph at beginning of run- added zero point to dissolution graph- real time clipped to +/- 15 sec- added Qt, Q, Q+5 to dissolution graph- removed background check- disabled any Multi-component features- SST is default, 1 std 1 reading, 1+6 std 2 readings- 1 minute accuracy in SP edit
- sp edit: linear only, but two time bases- Qt default 30 min, Q+5 default 75 %- removed component names from run info
- define Qt, Q, Q+5 in run info
- Std 1Conc, Std2 Conc in run info
- carrys over best integration time from ICC- infinty test included- flags SP results acc. to USP rpm +- 4%, T 37 +- 0.5 °C

Review 3.98

Phil Rogers (Pfizer) on site review at Zeiss, user interface design review

Release 0.8

Preliminary test release for Multicomponent Analysis

released : 2.98

not brought forth, archived at OEM-M2, further work from R 0.72

Release 0.4 - 0.72

Zeiss on-site test and demos

released : 4.97 – 3.98

Release 0.2

Revised and Signed Software Specification by Zeiss

released 21.04.1997

Review 02.04.97

Comments on Software Spec by Pfizer (FAX 2/4/97)

Release 0.1

Proposal of software specification by Zeiss

released 20.12.1996

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

43

Supplements

44

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software SpecificationZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

45

Algorithm for smoothing and derivatives according to Savitzky-Golay
Smoothed spectra and their derivatives are computed according to the Savitzky-Golay
algorithm. This fast numerical procedure provides the new data points using a set of predefinedcoefficients.

y new
=
j

n

1

coeff

(

⋅ ∑ y old
j + i − ( n +1) / 2 ⋅ coeff
n +1

i =1

)

The spectra to be processed must be of equidistant. type, i.e. the x-data points must be
evenly spaced by ∆X. The standard SG coefficients are computed for a ∆X of 1.
The coefficients have been computed according to R. Ludwig [see "Methoden derFehler- und Ausgleichsrechnung"; VEB Deutscher Verlag der Wissenschaften, Berlin
1969 ].
Coefficients for smoothing,using n points
i
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26

n=5
-3
12
17
12
-3
35

n=7
-2
3
6
7
6
3
-2
21

n=9
-21
14
39
54
59
54
39
14
-21
231

n=11
-36
9
44
69
84
89
84
69
44
9
-36
429

Coefficients for derivatives
(n=9)
n=13
-11
0
9
16
21
24
25
24
21
16
9
0
-11
143

n=17
-21
-6
7
18
27
34
39
42
43
42
39
34
27
18
7
-6
-21
323

n=21 n=25-171 -253-76 -138
9
-33
84
62
149 147
204 222249 287284 342309 387324 422329 447
324 462309 467
284 462249 447
204 422149 387
84 3429 287-76 222-171 147
3059
62
-33
-138
-253
5175

i
1
2
3
4
5
6
7
8
9
10

1st
-4
-3
-2
-1
0
1
2
3
4
60

2nd
28
7
-8
-17
-20
-17
-8
7
28
462

3rd
-14
7
13
9
0
-9
-13
-7
14
198

4th
14
-21
-11
9
18
9
-11
-21
14
143

The described algorithm is used in the ZEISS software to produce smoothed spectra and their derivatives.

46

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software SpecificationZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

47

Labview Graph Handles

The graph palette has controls for panning (scrolling the display area of a graph) and forzooming in and out of sections of the graph.

If you press the x autoscale button, LabVIEW autoscales the X data of the graph.
If you press the y autoscale button, LabVIEW autoscales the Y data of the graph. If
you want the graph to autoscale either of the scales continuously, click on the lockswitch, shown at the left, to lock autoscaling on.
The scale format buttons give you run-time control over the format of the X and Y
scale markers respectively.

You use the remaining three buttons to control the operation mode for the graph.
Normally, you are in standard operate mode, indicated by the plus or crosshatch. In
operate mode, you can click in the graph to move cursors around.
If you press the panning tool, shown to the left, you switch to a mode in which you canscroll the visible data by clicking and dragging sections of the graph.
If you press the zoom tool, shown at the left, you can zoom in on a section of the graph bydragging a selection rectangle around that section. If you click on the zoom tool and hold for a
moment, you get a pop-up menu you can use to choose some other methods of zooming. Thismenu is shown in the following illustration.

48

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

A description of each of these options follows.

Zoom by rectangle.
Zoom by rectangle, with zooming restricted to x data (the y scale remains
unchanged.
Zoom by rectangle, with zooming restricted to y data (the z scale remains
unchanged).
Undo last zoom. Resets the graph to its previous setting.
Zoom in about a point. If you hold down the mouse on a specific point, thegraph continuously zooms in until you release the mouse button.
Zoom out about a point. If you hold down the mouse on a specific point, thegraph continuously zooms out until you release the mouse button.

Note: For the last two modes, zoom in and zoom out about a point, shift clicking zooms in theother direction.

ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

49

Zeiss ASPECT plus data file format
author:E.Steinreleased :08.06.95

General remarks•

The header of the data file is similar to a windows-INI-file. To read a data file it is necessary
to interpret the sections GENERAL and DATA.
Every entry has to start at the beginning of a line. The section keywords are enclosed insquare brackets (’[’ and ’]’) and immediately followed by a CR/LF.

•

The keywords in the sections must befollowed immediately by an equal sign and then by thecorresponding value of the respective keyword (in GENERAL section). In theDATA section
the equal sign is to be followed immediately by a CR/LF. Here the first byte of the data has
to stand on the beginning of the next line. After the last byte of data a CR/LF is to be
appended.

•

All data are 4-Byte IEEE float values. ASPECT will accept values in the range(-1.0 E15 .... 1.0 E15) only.

•

The section GENERAL is always the first section in the data file.

•

Several more sections and keywords are defined for internal use and may occur in the data
files.

•

50

The data file should be opened in binary mode.

ZEISS Z-DIS UX MUX Dissolution Monitor V 09 - Software Specification

Format[GENERAL]TITLE=

small note of up to 50 characters

TYP=

0

old DOS-aspect format,

1

old DOS-aspect format,

2

old DOS-aspect format,

3

old DOS-aspect format,

4

current data file format

TIME=

date and time as a string in the format:
dd.mm.yyyy/hh:mm:ss

XUNITS=

unit of the abscissa values

YUNITS=

unit of the ordinate values

ZUNITS=

unit of the cycle values

FIRSTX=

start value of measurement range as string

LASTX=

end value of measurement range as string

NPOINTS=

number of measurement values per cycle as string

NCYCL=

number of cycles as string[DATA]ZDATA=

cycle values in a field of float values (data type float). The size of the
field (number of elements) is specified by keyword NCYCL. ZDATA is
not necessarily included in the data file, even if the number of cycles isgreater than 1 !

XDATA=

abscissa values in a field of float values. The size of the field isspecified by keyword NPOINTS. The abscissa values are the samefor all cycles.

YDATA=

measurement values in a field of float values. The size of the field is
NPOINTS * NCYCL. The cycle values are stored in subsequent
order (cycle 1, cycle 2, ...)ZEISS Z-DIS MUX MUX Dissolution Monitor V 0.9 - Software Specification

51