![]() ![]() For Pharmacopeial purposes, the melting range, melting temperature, or melting point is defined as those points of temperature within which, or the point at which, the first detectable liquid phase is detected to the temperature at which no solid phase is apparent, except as defined otherwise for Classes II and III below. A melting transition may be instantaneous for a highly pure material, but usually a range is observed from the beginning to the end of the process. Factors influencing this transition include the sample size, the particle size, the efficiency of heat diffusion, and the heating rate, among other variables, that are controlled by procedure instructions. In order to achieve consistency and repeatability during melting point determinations, the following conditions should be applied. Use dried material that has been gently pulverized and introduced into a capillary tube to a nominal height of 3 mm, and perform the melting determination at a heating rate of 1
![]() ![]() ![]() Eight procedures for the determination of melting range or temperature are given herein, varying in accordance with the nature of the substance. When no class is designated in the monograph, use the procedure for Class Ia for crystalline or amorphous substances and the procedure for Class II for waxy substances.
The procedure known as the mixed-melting point determination, whereby the melting range or temperature of a solid under test is compared with that of an intimate mixture of equal parts of the solid and an authentic specimen of it, e.g., the corresponding USP Reference Standard, if available, may be used as a confirmatory identification test. Agreement of the observations on the original and the mixture constitutes reliable evidence of chemical identity.
APPARATUS Apparatus with cameras or other computerized equipment with advantages in terms of accuracy, sensitivity, or precision may be used provided that the apparatus is properly qualified.
Apparatus I:
An example of a suitable melting range Apparatus I consists of a glass container for a bath of transparent fluid, a suitable stirring device, an accurate thermometer, and a controlled source of heat. The bath fluid is selected with a view to the temperature required, but light paraffin is used generally and certain liquid silicones are well adapted to the higher temperature ranges. The fluid is deep enough to permit immersion of the thermometer to its specified immersion depth so that the bulb is still about 2 cm above the bottom of the bath. The heat may be supplied by an open flame or electrically. The capillary tube is about 10 cm long and 0.8–1.2 mm in internal diameter with walls 0.2–0.3 mm in thickness.
Apparatus II:
An instrument may be used in the procedures for Classes I, Ia, and Ib. An example of a suitable melting range Apparatus II consists of a block of metal that may be heated at a controlled rate, its temperature being monitored by a sensor. The block accommodates the capillary tube containing the test substance and permits monitoring of the melting process, typically by means of a beam of light and a detector. The detector signal may be processed by a microcomputer to determine and display the melting point or range, or the detector signal may be plotted to allow visual estimation of the melting point or range.
PROCEDURES
Procedure for Class I, Apparatus I:
Reduce the substance under test to a very fine powder, and, unless otherwise directed, render it anhydrous when it contains water of hydration by drying it at the temperature specified in the monograph, or, when the substance contains no water of hydration, dry it over a suitable desiccant for NLT 16 h (or at the conditions stated in Loss on Drying
![]() ![]() Charge a capillary glass tube, one end of which is sealed, with a sufficient amount of the dry powder to form a column in the bottom of the tube 3 mm high when packed down as closely as possible by moderate tapping on a solid surface. Due to the instrument design, alternative sample sizes may be instructed by the instrument manufacturer.
Heat the bath until the temperature is about 10
![]() ![]() ![]() ![]() The temperature at which the column of the substance under test is observed to collapse definitely against the side of the tube at any point indicates the beginning of melting, and the temperature at which the test substance becomes liquid throughout corresponds to the end of melting or the melting point. The two temperatures fall within the limits of the melting range. If melting occurs with decomposition, the melting temperature corresponding to the beginning of the melting is within the range specified.
Procedure for Class Ia, Apparatus I:
Prepare the test substance and charge the capillary as directed in Procedure for Class I, Apparatus I. Heat the bath until the temperature is about 10
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Procedure for Class Ib, Apparatus I:
Place the test substance in a closed container and cool to 10
![]() ![]() ![]() If the particle size of the material is too large for the capillary, precool the test substance as directed above, then with as little pressure as possible gently crush the particles to fit the capillary, and immediately charge the tube.
Procedure for Class I, Apparatus II:
Prepare the substance under test and charge the capillary tube as directed in Procedure for Class I, Apparatus I. Operate the apparatus according to the manufacturer's instructions. Heat the block until the temperature is about 10
![]() ![]() The temperature at which the detector signal first leaves its initial value indicates the beginning of melting, and the temperature at which the detector signal reaches its final value corresponds to the end of melting, or the melting point. The two temperatures fall within the limits of the melting range. If melting occurs with decomposition, the melting temperature corresponding to the beginning of the melting is within the range specified.
Procedure for Class Ia, Apparatus II:
Prepare the test substance and charge the capillary as directed in Procedure for Class I, Apparatus I. Operate the apparatus according to the manufacturer's instructions. Heat the block until the temperature is about 10
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Procedure for Class Ib, Apparatus II:
Place the test substance in a closed container and cool to 10
![]() ![]() ![]() If the particle size of the material is too large for the capillary, precool the test substance as directed above, then with as little pressure as possible gently crush the particles to fit the capillary, and immediately charge the tube.
Procedure for Class II:
Carefully melt the material to be tested at as low a temperature as possible, and draw it into a capillary tube, which is left open at both ends, to a depth of about 10 mm. Cool the charged tube at 10
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Procedure for Class III:
Melt a quantity of the test substance slowly, while stirring, until it reaches a temperature of 90
![]() ![]() ![]() ![]() ![]() ![]() Fix the thermometer securely in a test tube so that the lower point is 15 mm above the bottom of the test tube. Suspend the test tube in a water bath adjusted to about 16
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USP38–NF33 Page 525
Pharmacopeial Forum: Volume No. 39(5)
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