6 mpdp routine maintenance guide EN

[°C/min] Own references substances US Pharmacopeia USP 37-NF32 Melting range: Evaluation of collapse and clear point 1 Yes, 6, range 83–237 °C Japanese Industrial Standard K 0064 1 °C/

Day-to-Day Routine Maintenance

of Melting & Dropping Point Instruments

Performance Verification

2 METTLER TOLEDO Automated Melting & Dropping Point Analysis

Disclaimer

The information contained in this guide is based on the current knowledge and experience of the authors The guide represents selected, possible application examples The experiments were conducted and the resulting data evaluated in our lab with the utmost care using the instruments specified in the description of each application The experiments were conducted and the resulting data evaluated based on our current state of knowledge However, this guide does not absolve you from personally testing its suitability for your intended methods, instruments and purposes As the use and transfer of an application example are beyond our control, we cannot accept responsibility therefore

When chemicals, solvents and gases are used, the general safety rules and the instructions given by the manufacturer or supplier must be observed.

® ™ All names of commercial products can be registered trademarks, even if they are not denoted as such

For almost 5 decades METTLER TOLEDO has provided instrumental solutions for the automatic determination

of the thermal values melting point, dropping and softening point The MP and DP Excellence lines, METTLER TOLEDO’s latest release of compact instruments for thermal characterization, support the complete analytical workflow with innovative solutions

In order to characterize a material aside from chemical analysis, primarily physical methods allow us to

differentiate between, identify and classify substances or to describe quality aspects Thermal characteristics, such as melting and dropping point provide valuable and accessible information in this respect

This guideline provides advice and tips for the routine maintenance of the melting point and dropping point instruments in the daily use

The MP and DP Excellence lines consist of the following instruments:

• Melting point: MP50, MP70, MP90

• Dropping and softening point: DP70, DP90

4 METTLER TOLEDO Automated Melting & Dropping Point Analysis

tion 2 Tips & Hints for Accurate Melting Point Determination A practical and rather easy way to check the performance of a melting point instrument is the comparison

with standard reference samples A periodically repeated comparison reveals immediately if instruments deviate from the regular and required performance, if calibration is requested or even if service has to be done For comparison purposes several sets of standard reference materials are available

2.1 Melting Point Standards Overview

The following table provides an overview of the melting point standards that are important for melting point determination The individual standards specify the measurement parameters, the experimental setup (e.g heating medium; oil bath or furnace), the capillary dimensions and the detection of the melting point event Some of the pharmacopeias offer their own reference substances that are recommended for use in the calibration/adjustment of the instrument The instruments of the MP Excellence line fully comply with these standards

[°C/min]

Own references substances

US Pharmacopeia USP 37-NF32 <741>

Melting range: Evaluation

of collapse and clear point

1 Yes, 6,

range 83–237 °C

Japanese Industrial Standard K 0064

1 °C/min

Yes, 12, range 60–280 °C

Evaluation of clear point

1 Yes, 12,

range 69–263 °C

chapter 2.2.60

Table 1: Melting point standards overview

The following tables include melting point test results

of reference substances from two different suppliers, USP and WHO, that were measured with an MP90

For each reference substance, the measurement was obtained by taking the mean value of six capillaries The results reveal the excellent measurement accuracy and repeatability that can be achieved with MP Excellence instruments The basis of these measurements is careful sample preparation which can easily be achieved using the capillary filling tool

Figure 1: USP reference substances

2.2.1 USP References

USP specifies that the measured melting range must

a) lie within the specified minimum and maximum temperatures (e.g 81–83 °C for vanillin), and

b) must not be broader than the specified admissible values (e.g 1.5 °C for vanillin) So, the permitted measured melting range for vanillin could be 81.0–82.5, 81.3–82.8 °C etc

Name of USP

reference substance

[°C]

min/max admissible range min/max range

TC: 0.05

TC: 0.00

TC: 0.05

TC: 0.04

TC: 0.07

Table 2: USP references (MR: melting range, Repeatability: 6 capillaries)

Six capillaries of each USP reference substance were measured simultaneously and the respective transmission curves were evaluated in the melting range mode, meaning the default parameters of points A and C were used

Conclusions

The accuracy and repeatability of the results obtained from the MP90 are excellent With each of the tested reference substances a melting range smaller than the admissible reference value was reached The absolute melting range values were all within the specification temperatures Hence, the MP90 instrument is ideally suited

to determine melting points according to USP

6 METTLER TOLEDO Automated Melting & Dropping Point Analysis

2.2.2 WHO References

WHO reference substances are specified with a maximum permissible temperature range, in the same way as the METTLER TOLEDO reference substances

The melting point criterion is the clear point C, when all solid material has been transformed into the liquid state

Name of WHO reference substance

[°C]

Table 3: WHO references (MR: melting range, Repeatability: 6 capillaries)

Conclusions

The MP90 achieved excellent results also with the WHO reference substances The melting points of all tested references were within specifications The achieved repeatability was far better than the assigned values Thus, the MP90 is best suitable to measure melting points following WHO guidelines

Figure 2: WHO reference substances

3 Tips & Hints for Accurate Dropping & Softening Point Determination

The procedure to check the performance of dropping and softening point instruments is similar to the melting point instrument check However, more strict rules apply in terms of suitable reference materials measurement parameters

If we want to make sure that our dropping point instrument

functions correctly, we need to verify its measurement

accuracy The following section gives valuable tips and

hints to help execute the performance verification correctly

In order to check temperature accuracy we use reference

substances and compare their nominal values, including

tolerances, with the measured values ("calibration") If the

measured temperature values are outside the values of the

certified reference substance, the instrument needs to be

adjusted ("adjustment")

METTLER TOLEDO reference substances such as

benzophenone, vanillin, benzoic acid and potassium nitrate provide certified temperature values that can be used for temperature calibration of the DP70 and DP90 furnaces It is highly recommended that METTLER

TOLEDO reference substances are used for calibration and adjustment purposes of DP Excellence instruments The substances are securely identified with two barcodes showing the filling code and lot number The quality of the substances is guaranteed and is monitored by DSC measurement

The DP70 and DP90 Excellence instruments include an

automatic procedure that compares the measured value

with the nominal value The basis for comparison is the

thermodynamic melting point of the reference substance

(referred to as calibration substance) that is detailed on

the corresponding certificate and includes measurement

uncertainty The thermodynamic melting point is the

physically correct melting point temperature of the actual

sample, not the furnace temperature, and is independent

of the experimental setup

The dropping point of a reference substance is not equal

to the thermodynamic melting point as the measured

temperature is actually the furnace temperature and

not the sample temperature Therefore, the furnace

temperature value needs to be adjusted using a

correction value, which is stored for each reference

substance in the instrument

The correction factor is substance-specific and

heating-rate dependent It corrects the measured furnace

temperature to the thermodynamic melting point of the

relevant substance The correction factors in the table are

valid for a heating rate of 0.2 °C/min

Figure 3: METTLER TOLEDO reference substances

Figure 4: DP screen shot Entry field for correction factor and refer-ence substance

Potassium nitrate -1.4

Table 4: Correction factors based on thermodynamic melting point

8 METTLER TOLEDO Automated Melting & Dropping Point Analysis

Cup lids

Handle

Collector glass

Benzoic acid

Stand Sample carrier

Sample preparation tool

Cups

Spatula and rod

Balls

Once this is done, the comparison between measured and nominal temperature values is given Furthermore the correction factor takes into account the viscosity of the molten reference sample that drops from the cup, which has an influence on the dropping point temperature The correction factors have been determined empirically by comparing the furnace temperature dropping point with the known thermodynamic melting point of the reference substance

If the measured values of the reference substances are

(b) are outside of the nominal temperature value ranges, performance is not ok In this case, the instrument

issues a warning It then needs to be adjusted

3.2 Sample Preparation

The basis for comparable and reliable results in dropping point and softening point analysis is repeatable sample preparation This is why we recommend to use the accessory box of the DP instruments including the patented sample preparation tool

3.2.1 Excellence Accessory Box

The DP accessory box is included in the standard delivery of the DP70 and DP90 It provides useful accessories for reliable sample preparation:

• The DP sample preparation tool that enables efficient and clean filling of up to 4 dropping and softening point cups with liquid or solid substances, including a handle to place or remove the tool's plate into an oven or a refrigerator

• Two tamping rods to press ground solid samples into dropping or softening point cups

• 2 softening and 2 dropping point cups made of chromium-plated brass

• 2 stainless steel balls according to ASTM D6090

• 2 cup lids with vent hole to close the sample-containing cup

• 6 glass cups for collection of liquefied or softened samples during the respective tests

• Sample carrier that holds two dropping or softening point cups with glass collectors and cup lids

• A stand that holds two sample carriers

• A spatula to transfer the sample into a cup or to remove excessive sample

• A rod to remove excessive lubricant grease from a dropping point cup according to the procedure specified in ASTM D556

Figure 5: DP accessory box

Sample

preparation tool

3.2.2 Efficient and Reliable Sample Preparation: The Sample Preparation Tool

The basis for comparable and reliable results in dropping point and softening point analysis is repeatable sample preparation With the DP Excellence sample preparation tool this crucial step is perfectly supported:

• Efficient sample preparation as four cups can be prepared at a time

• Handling errors are minimized and operational security maximized

• Contamination of the outer surface of the sample cup is avoided which contributes to result reliability

The sample preparation tool consists of four pieces:

• A double-sided base plate that holds four dropping point cups on one side and four softening point cups on the other

• A support disk with four holes

• A disk-like funnel for powdered samples

• A handle to carry the whole tool (not shown in the pictures)

Dropping point cups are positioned on the side of the base plate with the deepest indentations The shallower indentations on the other side of the plate are used for positioning the softening point cups

A support disk is used to fix the cups and to make the upper rim of the cup level with the surface The support disk therefore serves a threefold purpose: first to prevent the sample from contaminating the outer surface

of the cups, second to facilitate the removal of excessive sample, and third to facilitate the complete filling of the sample cup with powdered samples

3.2.3 DP Excellence Sample Holder and Standard Compliant Cups

Standardized dropping and softening point cups from METTLER TOLEDO

are made of chromium-plated brass or aluminium The experimental setup required for an automatic dropping and softening point test consists

of the sample-containing cup, closed with a lid, and a collection glass underneath to collect the liquefied sample The sample carrier allows the efficient, simultaneous measurement of two samples, which are placed with the sample carrier into the DP furnace After test completion the sample carrier is removed from the furnace and securely placed on the stand to cool down to ambient temperature

It is then quickly disassembled and the collection glasses are put into the waste with the aluminium dropping

or softening point cups Cup lids prevent discharge of expanding sample, which avoids contamination of the

Cup Lids

Cups

Collection glass Stand

Figure 6: Work sequence with sample preparation tool

10 METTLER TOLEDO Automated Melting & Dropping Point Analysis

furnace

Tedious and time-consuming work in dropping and softening point analysis involves cleaning the components after completion of the analysis Unhealthy, nonpolar solvents may be required in order to dissolve the sample residues The DP Excellence system provides disposable aluminium sample cups and glass sample-collectors that make cleaning unnecessary The post-treatment process is therefore significantly accelerated and the system is ready for the next measurements within a short time The DP Excellence solution is therefore much more efficient than other competitor systems that require complete cleaning of the sample holder prior to the next analysis

4 How to Clean the Dropping Point Furnaceon

Thermal treatment under pure oxygen atmosphere

or ambient air is recommended, if the furnace of a

DP70 or DP90 Excellence dropping point system

is contaminated with decomposition products that

originated from thermal decomposition of the samples

such as lubricant grease during dropping point tests

However, best practice is to avoid having to clean

the furnace This is achieved by preparing samples

carefully and making sure that the sample carrier,

cups and cup lids are free of residue Nevertheless, the

area around the sample carrier can still become sticky

over time and request removal of such decomposed

materials

• The video image has darkened and may require adjustment of the brightness factor

• During startup of the instrument the furnace position may not be accurately detected anymore Then a

respective error message will appear to alert the user and to indicate that default parameters for furnace position detection are being used

4.2 Cleaning procedure

Please adhere to the general lab safety measures and instrument safety as described in the operating instructions If you are unsure about the cleaning procedure, please contact METTLER TOLEDO first for service advice

Instead of disassembling the furnace followed by thorough manual cleaning with solvents or abrasive materials,

a thermal treatment is recommended

Apply pure oxygen gas and heat the furnace to 400 °C until clean At this temperature the decomposed materials are oxidized to carbon dioxide Usually a one hour treatment is sufficient to clean the contaminated parts If necessary the procedure shall be repeated

Figure 10: Cross section view of a DP70 The furnace and the cam-era glass that may be contaminated with decomposition products