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 some articles, the melting process is accompanied by simultaneous decomposition, which is visually evidenced as a side event like darkening of the material, charring, bubbling, or other incident. The visual impact of this side reaction frequently obscures the end of the melting process, which it may be impossible to accurately determine. In those circumstances, only the beginning of the melting can be accurately established; and it is to be reported as the melting temperature. The accuracy of the apparatus to be used as described below should be checked at suitable intervals by the use of one or more of the available USP Melting Point Reference Standards, preferably those that melt nearest the melting temperatures of the compounds being tested (see USP Reference Standards 11).

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.

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 2.5 to 3.5 mm high when packed down as closely as possible by moderate tapping on a solid surface.

Heat the bath until the temperature is about 30 below the expected melting point. Remove the thermometer, and quickly attach the capillary tube to the thermometer by wetting both with a drop of the liquid of the bath or otherwise, and adjust its height so that the material in the capillary is level with the thermometer bulb. Replace the thermometer, and continue the heating, with constant stirring, sufficiently to cause the temperature to rise at a rate of about 3 per minute. When the temperature is about 3 below the lower limit of the expected melting range, reduce the heating so that the temperature rises at a rate of about 1 to 2 per minute. Continue heating until melting is complete.

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.

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.

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. In the event of dispute, only the melting range or temperature obtained as directed for Class I, Apparatus I, is definitive.

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. In the event of dispute, only the melting range or temperature obtained as directed for Class Ib, Apparatus I, is definitive.

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, and raise the temperature of the bath at the rate of 2 per minute to 30, then change to a rate of 1 per minute, and note the temperature at which the first drop of melted substance leaves the thermometer. Repeat the determination twice on a freshly melted portion of the test substance. If the variation of three determinations is less than 1, take the average of the three as the melting point. If the variation of three determinations is 1 or greater than 1, make two additional determinations and take the average of the five.