Loss on drying and validation of Moisture Analyzers

Transcription

1 Loss on drying and validation of Moisture Analyzers S.ZALI M.Sc. Dept. of Physico chemistry Razi vaccine serum research institute 1389/8/12

2 WATER DETERMINATION (921) Many Pharmacopeial articles either are hydrates or contain water in adsorbed form. As a result, the determination of the water content is important in demonstrating compliance with the Pharmacopeial standards. Generally one of the methods is called for in the individual monograph, depending upon the nature of the article. In rare cases, a choice is allowed between two methods. USP30 NF25 Page 385

3 WATER DETERMINATION (921) When the article contains water of hydration, the Method I (Titrimetric), the Method II (Azeotropic), or the Method III (Gravimetric) is employed, as directed in the individual monograph, and the requirement is given under the heading Water. The heading Loss on drying (see Loss on Drying 731 ) is used in those cases where the loss sustained on heating may be not entirely water. USP30 NF25 Page 385

4 Water and Loss on Drying Where the water of hydration or adsorbed water of a Pharmacopeial article is determined by the titrimetric method, the test is generally given under the heading Water. Monograph limits expressed as a percentage are figured on a weight/weight basis unless otherwise specified. Where the determination is made by drying under specified conditions, the test is generally given under the heading Loss on drying. However, Loss on drying is most often given as the heading where the loss in weight is known to represent residual volatile constituents, including organic solvents as well as water. USP30 NF25 Page 385

5 LOSS ON DRYING (731) The procedure set forth in this chapter determines the amount of volatile matter of any kind that is driven off under the conditions specified. For substances appearing to contain water as the only volatile constituent, the procedure given in the chapter, Water Determination 921, is appropriate, and is specified in the individual monograph. USP30 NF25 Page 300

6 LOSS ON DRYING (731) Mix and accurately weigh the substance. If the test specimen is in the form of large crystals, reduce the particle size to about 2 mm by quickly crushing. Tare a glass stoppered, shallow weighing bottle that has been dried for 30 minutes under the same conditions Put the test specimen in the bottle. By gentle, sidewise shaking, distribute the test specimen as evenly as practicable to a depth of about 5 mm generally. Place the loaded bottle in the drying chamber. Dry the test specimen at the temperature and for the time specified. USP30 NF25 Page 300

7 LOSS ON DRYING (731) If the substance melts at a lower temperature than that specified for the determination of Loss on drying, maintain the bottle with its contents for 1 to 2 hours at a temperature 5 to 10 below the melting temperature, then dry at the specified temperature. Where the specimen under test is Capsules, use a portion of the mixed contents of not fewer than 4 capsules. Where the specimen under test is Tablets, use powder from not fewer than 4 tablets ground to a fine powder. USP30 NF25 Page 300

8 LOSS ON DRYING (731) Where the individual monograph directs that loss on drying be determined by thermogravimetric analysis, a sensitive electro balance is to be used. Where drying in vacuum over a desiccant is directed in the individual monograph, a vacuum desiccator or a vacuum drying pistol, or other suitable vacuum drying apparatus, is to be used. Where drying in a desiccator is specified, exercise particular care to ensure that the desiccant is kept fully effective by frequent replacement. USP30 NF25 Page 300

9 LOSS ON DRYING (731) Where drying in a capillary-stoppered bottle in vacuum is directed in the individual monograph, use a bottle or tube fitted with a stopper having a 225 ± 25 μm diameter capillary, and maintain the heating chamber at a pressure of 5 mm or less of mercury. At the end of the heating period, admit dry air to the heating chamber, remove the bottle, and with the capillary stopper still in place allow it to cool in a desiccator before weighing. USP30 NF25 Page 300

10 XM120 Moisture Analyzer Developed for users with highest requirements and a wide range of samples High end instrument, conforming to the most stringent International standards Fastest sample optimum precision analysis

11 Introduction Top quality technology Weighing technology which meets all international metrological regulations Weighing range 124 g / readability of balance 1 mg High temperature range up to 230 C, temperature increments of 1 C, results displayed to 0.01% 3.4" VGA touch-screen graphic display Graphic print-out (RS232 interface) Extended method memory capacity Choice of radiation heat source: halogen, quartz infrared, dark infra-red

12 Introduction Simple controls Icon driven user guidance Variety of start-up and end-point control selections Three-phase drying for total control Easy access sample holder Practical construction to enable easy cleaning

13 Introduction Quality Assurance Results displayed in GLP guideline format. Numerical and statistical analysis available Real-time results shown in graphic display Download latest software through the internet

14 Technical Data Moisture Analysers

15 CLEANING Procedure: 1) Unplug the unit. 2) Allow the unit to cool for at least thirty (30) minutes. 3) Check that the unit is still unplugged. 4) Use a mild detergent and a soft rag to clean the external surfaces of the unit. CAUTION: Do not immerse unit in water or any other cleaning solution. 5) Carefully remove the weighing pan, draft shield and sample holder to thoroughly clean them.

16 CLEANING 6) Keep all warning labels clean. 7) Clean the chamber and other parts. Use extreme care in removing the accumulated residue with a clean, damp cloth. 8) Keep the mechanical part of the printer free from dirt and dust. Periodically lift up the printer cover to clean the printer mechanism with a soft brush.

17 Calibration Balance Calibration Temperature adjustment

18 Balance Calibration Enter a user-definable weight as a criterion for calibration in "ext.- def." mode

19 Balance Calibration The instrument performs a zero point measurement ( g is displayed flashing) The instrument performs a zero point measurement (0000 g is displayed flashing After the zero point measurement, the display flashes the recommended calibration weight ( g) or the weight defined by you. Place the calibration weight on. The display flashes Once the display stops flashing, this indicates that the calibration has ended.. The measured weight is displayed.

20

21 Temperature adjustment

22 Temperature adjustment Temp.-1. Set, C: First target temperature. You can enter other target temperatures according to your samples. (default 100 C).. Act, C: Temperature which was actually reached. If the temperature adjustment tool is connected, the temperature is automatically copied over from the temperature adjustment tool. Otherwise, it has to be input manually.. Temp.-2. Set, C: Second target temperature (default 160 C).. Act, C: Temperature which was actually reached. If the temperature adjustment tool is connected, the temperature is automatically copied over from the temperature adjustment tool. Otherwise, it has to be input manually.

23

24

25 Linearity A balance is linear when the displayed weight is equal (within the tolerance specified) to the actual weight, for weights between minimum and maximum capacity. To determine if the unit is linear, the same test mass is weighed at two pre-loads.

26 Repeatability (Balance) Number Average= Standard deviation= RSD= Weight=100gr E E-4 Weight=1gr E E-2

27 Thermogravimetric Analysis Thermogravimetric analysis involves the determination of the mass of a specimen as a function of temperature, or time of heating, or both, and when properly applied, provides more useful information than does loss on drying at fixed temperature, often for a fixed time and in what is usually an ill-defined atmosphere. Usually, loss of surface-absorbed solvent can be distinguished from solvent in the crystal lattice and from degradation losses. The measurements can be carried out in atmospheres having controlled humidity and oxygen concentration to reveal interactions with the drug substance, between drug substances, and between active substances and excipients or packaging materials. USP30 NF25 Page 377

28 Thermogravimetric Analysis While the details depend on the manufacturer, the essential features of the equipment are a recording balance and a programmable heat source. Equipment differs in the ability to handle specimens of various sizes, the means of sensing specimen temperature, and the range of atmosphere control. Calibration is required with all systems, i.e., the mass scale is calibrated by the use of standard weights; calibration of the temperature scale, which is more difficult, involving either variations in positioning of thermocouples and their calibration; or in other systems, calibration involves the use of standard materials because it is assumed that the specimen temperature is the furnace temperature. USP30 NF25 Page 377

29 Thermogravimetric Analysis Procedural details are specified in order to provide for valid interlaboratory comparison of results. The specimen weight, source, and thermal history are noted. The equipment description covers dimensions and geometry, the materials of the test specimen holder, and the location of the temperature transducer. Alternatively, the make and model number of commercial equipment are specified. In all cases, the calibration record is specified. Data on the temperature environment include the initial and final temperatures and the rate of change or other details if nonlinear. The test atmosphere is critical; the volume, pressure, composition, whether static or dynamic, and if the latter, the flow rate and temperature are specified. USP30 NF25 Page 377

30 Validation of facility systems and equipment The validation protocols for equipment and systems are normally divided into three segments: IQ, OQ, PQ. For systems and equipment, Performance Qualification is often synonymous with Validation. Depending on the function and operation of some equipment, only IQ/OQ are required. For equipment whose correct operation is a sufficient indicator of its function, and that are monitored and/or calibrated on a regular schedule (e.g. ph meter, incubator, centrifuge, freezer), the installation and operational qualifications are performed. Systems such as air, water, steam, and major equipment which perform critical support processes, such as sterilization (autoclave, oven), depyrogenation (oven or tunnel), or lyophilization, require installation, operational and performance qualifications. A WHO guide to good manufacturing practice (GMP) equirements Part 2: Validation

31 Validation of facility systems and equipment The following table lists the typical categories of systems and equipment which require performance qualification Systems Equipment Air (HVAC) Autoclave Compressed air Depyrogenation oven or tunnel Pure Steam Lyophilizer Raw steam Continuous flow centrifuge Purified water WFI Central vacuum A WHO guide to good manufacturing practice (GMP) equirements Part 2: Validation

32 Installation qualification(iq) The IQ should list all the identification information, the location, utility requirements and any safety features of the equipment. The IQ protocol prepared for each piece of equipment or system lists the name, description, model and identification numbers, the location, utility requirements, connections, and any safety features of the system/equipment which need to be documented. It should verify that the item matches the purchase specifications, and that all drawings, manuals, spare parts list, vendor address and contact number, and other pertinent documentation are available. A WHO guide to good manufacturing practice (GMP) equirements Part 2: Validation

33 Operational qualification (OQ) This document outlines the information required to provide evidence that all the components of a system or of a piece of equipment operate as specified. This involves testing of all normal operation controls, all alarm points, all switches and displays, interacting controls, and any other indications of operations and functions. The OQ document should provide a listing of SOPs (or reference to specific manual instructions) for operation, maintenance and calibration; information on the training of operators; and instructions for any static or dynamic tests to show that the equipment operates as expected under normal conditions. Specifications and acceptance criteria must be defined for all the operations. The OQ document should include information on equipment or system calibration, preoperational activities, routine operations and their acceptance criteria. A WHO guide to good manufacturing practice (GMP) equirements Part 2: Validation

34 Performance qualification (PQ) This part of the validation for systems and equipment is performed after both Installation and Operational Qualifications have been completed, reviewed and approved. The PQ document describes the procedure or procedures for demonstrating that a system or piece of equipment can consistently perform and meet required specifications under routine operation and, where appropriate, under worst case situations. The PQ should include a description of the preliminary procedures required, the detailed performance test(s) to be done, and the acceptance criteria for each test. The PQ also requires that other supporting equipment used during the qualification have been validated (e.g. the steam system must be validated before the autoclave can be validated). A WHO guide to good manufacturing practice (GMP) equirements Part 2: Validation

35