Focusing on Pharmacy The Analysis, Characterization and Identification of Substances

5/24/2018 Focusing on Pharmacy The Analysis, Characterization and Identification of Substances

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Focusing on PharmacyThe Analysis, Characterization and Identification of Substances


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Company founder Thomas NETZSCH(1845 - 1897), born in Selb, Germany

Expertise in Thermal Analysis

The NETZSCH Company was founded in 1873 inSelb, Germany, by the brothers Thomas and ChristianNetzsch. Today, it is a sound, medium-sized, family-run company specializing in the manufacturing ofmachines and measuring instruments. As a globalinnovator, Netzsch continues to grow its three busi-ness units of 2,100 employees in the manufacturing,sales and service divisions.

Analyzing & Testing

Grinding & Dispersing

Pumps

Flame Photometer from 1958


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Experts in Thermal Analysis for over 50 years

As early as 1953, the Analyzing & Testing businessunit began developing and manufacturing thermo-analytical instruments. In 1962, NETZSCH-Gertebauwas registered as an independent limited company.

Its headquarters are still located in Selb, where themajority of the measuring instruments are manu-factured, including all instruments for differentialscanning calorimetry (DSC), thermogravimetry (TG)and simultaneous thermal analysis (STA). NETZSCHtechnology is made in Germany and it istechnology you can rely on.

Since its inception, NETZSCH has been continuouslyexpanding its library of applications and solidifyingits role as an expert in Thermal Analysis. Today,NETZSCH offers a complete product line of instru-ments for research, development and qualityassurance. Cutting edge technology, premium

service, and high quality standards make NETZSCH aleading manufacturer.

NETZSCH Your Partner for Thermal Analysis.


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Quality and Service Come First

Chemical and pharmaceutical research, development,and manufacturing all place high demands on thesecurity, accuracy, dependability and reproducibilityof the analytical methods employed. NETZSCH instru-ments set high standards in these areas with regardto precision, flexibility and consistency.

For Thermal Analysis, the Pharmacopoeia of Europe(Ph. Eur., chapter 2.2.34) and the United States (USP,

chapter 891) describe the methods for differentialscanning calorimetry (DSC) and thermogravimetry(TG or TGA). These methods can be utilized for thecharacterization of both pure substances and mix-tures. Thermal Analysis yields valuable informationabout the physical-chemical properties of suchmaterials.

The coupling of thermobalances to gas analysissystems such as mass spectrometers (QMS, quadru-pole mass spectrometer) or FTIR instruments (FourierTransform Infrared Spectroscopy) expands thespectrum of analysis and allows for conclusions to

be drawn on evaporation processes (release ofsolvents, sublimation) or changes in the chemicalcomposition (water release from hydrates, de-

composition) of active pharmaceutical ingredients,additives and formulations..

Typical application fields for DSC, TG:

Purity testing

Determination of melting of glass transitiontemperatures

Polymorphic studies

Investigation of interaction betweencomponents

Determination of thermal stabilities

Analysis of composition

Studies of decomposition kinetics


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Methology:

A DSC measures the change in heat balance (heatabsorption or heat release) of a sample duringheating or cooling as compared to an inert reference.With a thermobalance (TG), the mass change of a

sample can be determined as a function of temper-ature or time. Simultaneous thermal analysis (STA)combines both methods in one instrument.

The customer is our focus!

It is our philosophy to provide you with a completesolutions packages specially tailored to yourneeds for the successful accomplishment of yourtasks. Along with our high-performance instruments,we offer you measurement and evaluation softwareconforming to 21 CFR part 11 (FDA regulationElectronic Records, electronic signatures), flexiblequalification documents (IQ-OQ), individually

designed service plans, on-site calibration service, avariety of training options, and expert applicationsupport. Our qualified staff from the applications,laboratory, technical service and training departmentswill be pleased to discuss your requirements from

selecting appropriate measurement parameters tointerpreting the results. Various seminars, usersmeetings and individual customer training sessionscan help you tap into the full potential of yourthermoanalytical systems and get optimal results.

We look forward to sharing our decades of hands-onexperience with you. You can find plenty of applica-tion examples in our book entitled Characterizationof Pharmaceuticals, on our website, or in ourcustomer magazine (OnSet) published twice a year..

Put your faith in us!


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Superior Service

Optimal customer service and worldwide support aretrademarks of NETZSCH.

Our training department offers a wide variety ofevents, tailored to the needs of users from research,education and industry. Our application laboratoriesare expert partners for contract testing and our

scientists work out individual solutions to your labsspecific requirements.

In addition, NETZSCH Analyzing & Testing offers abroad range of instrument-specific services. TrainedNETZSCH employees in more than 45 service centersworldwide provide fast, reliable customer support forinstallation and commissioning, calibration or main-tenance.

What NETZSCH offers

Installation, commissioning and initialqualification of your instruments

Installation and commissioning include a com-plete configuration and parameterization of your

instrument, as well as comprehensive instructionfor your operators. After successful commis-sioning, our service engineers carry outthe installation qualification (IQ), operationqualification (OQ) and assist you with theperformance qualification (PQ). The type andextent of the documentation is designed aroundyour requirements.

Hotline service

Our experienced service staff is happy to provideyou with assistance by telephone and e-mail.Inquiries are normally handled within 24 hours.


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Flexible qualification agreements andcalibration service

You decide how often your instrument should beinspected this guarantees that your mainte-nance schedule is customized to your needs. Our

clearly structured service price list makes plan-ning and budgeting straightforward and mini-mizes your administrative efforts. Your servicehistory manual gives you an overview of theinstrument configuration and the schedulingfor your next instrument qualification.

To make sure that your Netzsch instrument stillcomplies with the corresponding specificationsand standards after extended operation, ourservice team will coordinate with you systemcheck-ups. On request, we will also carry out re-qualifications after a software update is installed.All members of our expert service staff receive

continuing education in maintenance, repair andvalidation on a regular basis. We can guaranteean efficient and professional service perfor-mance.

On-site repairs and spare part service

Diagnostic systems implemented within NETZSCHinstruments enable quick and efficient problemsolving. Any problems are immediately localized

and service quickly restored.

For newly installed instruments, we guaranteespare part availability for at least 10 years.Almost any spare part can be shipped from ourwarehouse within two working days after receiptof your order. Should on-site repair be impos-sible, our exchange and loan services will offeryou a suitable component replacement for theduration of the repair time.


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Ribavirin

DSC is used for studying the melting behavior ofcrystalline samples. The standardized DSC evaluationmethods determine the melting point as an extra-polated onset. The peak area is proportional to themelting enthalpy. The temperature difference be-tween the beginning of melting (extrapolated onset)and the temperature at which the entire sample ismelted (peak maximum) is dependent upon thesample amount, among other variables. Opticalmethods such as the capillary method show thetemperature at which the sample no longer containsany crystalline (diffusing) portion, which correspondsto the peak maximum of the DSC curve. The begin-ning of melting cannot always be clearly determined

by means of the capillary method.

Deoxyribonucleic acid (DNA)

During thermal treatment of deoxyribonucleic acid(DNA), a structural transition occurs from the helicalstructure to isolated single strands. This transitioncan be observed as an endothermal effect in the DSCthermogram (red). By plotting the heat flow versustime during the transition as an integral (blue), thetemperature at which 50% of the helical structurehas become single strands can be determined. Thistemperature is a measure of the stability of the helix

and is also designated as the melting temperature ofDNA.

Applications


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Diclofenac sodium

Many powdery solids tend to adsorb moisture(deliquescence) or form pseudopolymorphs(solvates). Diclofenac sodium shows no tendency tobind water at 40C up to a relative humidity of50%. At a relative humidity of 75%, however, awater absorption of 29% occurs. If the moisturecontent of the sample atmosphere is then reducedagain to 5%, the release of water can be observedby means of the TG signal; the reversibility of thewater absorption can thereby be confirmed. Theexposure of active ingredients and formulations at40C and a relative humidity of 75% serves fortesting storage stability in climates with high humid-ity.

In both research and production related monitoring, it is important to analyze properties such as melting behavior, purity,thermal stability, decomposition behavior and the absorption of moisture during storage. The following examples show theversatile possibilities for employing thermal analysis instrumentation in pharmaceutical applications.

-Lactose monohydrate

By investigating -lactose monohydrate with the STA449 Jupiter, simultaneous TG and DSC data can beobtained with one measurement. By the mass loss of4.91% along with the endothermal signal at 144C,dehydration of -lactose mono-hydrate to water-free-lactose. The energetic effects at 165C and 171C,however, are not connected with a mass change andcan therefore be interpreted as structural phasetransitions. The decomposition is shown by the mass

loss in the TG curve and already starts at the begin-ning of the melting process of water-free -lactose.


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Applications

Aminobenzoic acid

The gas-tight design of the DSC 204 F1Phoenix

allows it to be directly combined with instrumentsfor Fourier Transform Infrared Spectroscopy (FTIR)and mass spectrometry (MS). This enables not onlythe recording of caloric effects for the sample, butalso the identification of evolving gaseous sub-stances (like residual solvents or humidity). Amino-benzoic acid decomposes immediately after melting(peak temperature: 192C). The mass-to-charge ratio(amu) detected in the mass spectrometer enables theidentification of the investigated substance and itsfragments.

Maltose monohydrate

The coupling of a DSC 204 F1Phoenix to a FourierTransform Infrared Spectrometer (FTIR) allows,among other things, for the monitoring of gasrelease during dehydration of hydrates. Even whenusing temperature programs providing severalheating and cooling cycles, FTIR data can be recod-ed continuously. This is implemented during themeasurements as the Gram-Schmidt trace in thethermoanalytical evaluation software. The exampleused here is maltose monohydrate. The sampledehydrates during the first heating and is present asan amorphous anhydrate during cooling. In thesecond heating, the glass transition and subsequentdecomposition can be observed.


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Melting behavior of biphenyl (C12H10)

Based on the Vant Hoff approach, impurities ineutectic mixtures can be quantified in a concentra-tion of


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Proteus Pharm is an efficient, easy-to-operate

software combining all regulatory requirements(technical compliance) with a maximum of

flexibility and user friendliness.One can upgrade to advanced modules, such astemperature-modulated DSC (TM-DSC*), determina-

tion of specific heat (cp), determination of the calcu-lated DTA signal (c-DTA), automation of evaluationswith integrated result monitoring (macrorecorder) or

purity determination at any point in time. Someadvanced options are already included in the soft-ware of the F1 series instruments, specially designed

for research & development.

* TM-DSC not available in North America and Japan

In 1997, the United States Food and Drug Admin-istration (FDA) published regulations defining re-quirements for electronic records and criteria for theuse of electronic signatures. The objective of theseguidelines known as 21 CFR Part 11 after thelocation of their publication is the complete trace-ability of processes in the development, approvaland production of drugs and medical products.

Proteus Pharm- a Customized Software Solution

All-in-one concept

Even the basic version of the software programincludes all relevant functions for the evaluation andgraphical presentation of DSC or TG measurements.These include:

Determination of onset, peak, end temper-atures as well as inflection points

Analysis of peak areas (enthalpies) and partialpeak areas with selectable baseline

Evaluation of glass transitions

Determination of mass-loss steps

Calculation and presentation of 1st and 2nd

derivatives

Extensive graphical choices

Graphic and data export


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Effectice security system independent of theWindows operating systems:

The software can be adapted to almost any laborganization despite its regulated built-in securitysystems. Apart from the request to enter a user

name and password when opening the software,the user will not notice any difference during themeasurement and evaluation as compared to aprogram which does not comply with the FDAregulations.

A combination of user name and password servesto identify authorized personnel. Unauthorizedaccess attempts are recorded reliably and result ina blocking of the corresponding user account. Thisblocking can only be cancelled by the authorizedsafety administrator.

Audit Trail:

Proteus Pharm keeps two logs in which all rele-vant actions are recorded (who has done what whenand why). One audit trail is connected to the safetysystem, the second one to the measurement andevaluation part of the software.

Database orientation with convenient searchpossibilities:

Proteus Pharm supports the two databasesystems, Microsoft SQL Server and Oracle. Thismakes it possible to search not only by file namebut also by any entries made during the parameterdefinition. For example, a listing of all measurementsof a certain sample carried out during the last two

months can be generated in a matter of only a fewseconds

Electronic signatures:

Electronic signatures can also be activated ordeactivated with one simple click of the mouse.Best conditions for working in the hybrid mode.

Method editor:

With the method editor, measurement instructions(SOPs = standard operation procedures) can beformulated independently from the instrument,computer or instrument configuration.

For all users bound to conformity with 21 CFR Part11, Proteus Pharm is the ideal solution. For areasindependent from this guideline, we recommend ourproven NETZSCH Proteus software.


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TG 209 F3 Tarsus

Reliable thermobalance for quality assuranceand process optimization

Top-loading balance; fast and easy to operate

Gas-tight construction

Determination of the calculated DTA signal(c-DTA)

Automatic sample changer (optional) for up to20 samples

The Right Instrument for Every Application

DSC 200 F3 Maia

Robust, reliable DSC for routine applications

Easy handling

Great variety of accessories

Low maintenance costs


TG 209 F1 Iris - FTIRSTA 449 F1 Jupiter - FTIR

High-resolution, high-performance combina-tion for the characterization and identificationof gaseous products

Heated transfer line to prevent condensation


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* not available in North America and Japan

TG 209 F1 Iris

Highly precise mirco thermobalance for use inresearch & development

Vacuum-tight design

Pre-configured for coupling to gas analysissystems (FTIR or MS)

High sample throughput by means of fastheating and cooling rates

Automatic sample changer (optional) for up to64 different crucibles

DSC 204 F1 Phoenix

Dynamic differential scanning calorimeter tomeet highest requirements

Various sensors, optimized for different appli-cation fields

Temperature-modulated DSC (TM-DSC)*

Pre-configured for coupling to gas analysissystems (FTIR or MS)

Automatic samples changer (optional) for upto 64 different samples

STA 449 F1 Jupiter

Unrivalled flexibility in simultaneous thermalanalysis

Thermo nanobalance with a digital resolutionof 0.025g

Modular concept

A variey of furnaces and samples holders



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www.netzsch.com NGBGBPharmaE15000608MMM

Service at NETZSCH means worldwide competence, professionalism and the highestlevel of customer satisfaction.You can count on us!

Asia:NETZSCH Instruments Co., Ltd.

Room 2402-05, Unicom International Tower,547 Tianmu Road (W)Shanghai 200 070ChinaPhone: +86 21 63532705Fax: +86 21 63532704E-mail: [email protected]

Americas:NETZSCH Instruments, Inc.37 North AvenueBurlington, MA 01803USAPhone: +1 781 272 5353Fax: +1 781 272 5225E-mail: [email protected]

Europe:NETZSCH-Gertebau GmbHWittelsbacherstrae 4295100 SelbGermanyPhone: +49 9287 881-110Fax: +49 9287 881-505E-mail : [email protected]

NETZSCH Korea Co. Ltd.5F, Jaeneung Bldg., #1294-3, Beaksuk-DongIlsan-Gu, KoyangKoreaPhone +82 31 907-3193Fax: +82 31 908-3198

E-mail: [email protected]

Focusing on Pharmacy The Analysis, Characterization and Identification of Substances

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