Introduction of Melting Point Determination

There are generally three methods for the determination of melting point. The first method is to measure solid medicines that are easily crushed; the second method is to measure solid medicines that are not easily crushed (such as fats, fatty acids, paraffin, lanolin, etc.); the third method is to determine petrolatum or other Similar substances. When not specified under each item, it refers to the first method. According to the different properties of the substance to be tested, the determination method is divided into the following three types. The first method: when not specified under each item, it refers to the first method, which is to measure solid medicines that are easy to crush. Take the appropriate amount of the test product and grind it into a fine powder. Unless otherwise specified, it should be dried according to the conditions of drying and weightlessness of each drug. If the drug is a test product that does not check dry weight loss, the lower limit of the melting point range is above 135 ° C, and does not decompose when heated, it can be dried at 105 ° C; the test product with a melting point below 135 ° C or thermally decomposed can be used in pentoxide Dry in a phosphor dryer overnight or use other suitable drying methods, such as constant temperature and reduced pressure drying. Take the appropriate amount of the test product and place a capillary for the determination of melting point (referred to as capillary, made of neutral hard glass tube, more than 9cm long, inner diameter 0.9 ~ 1.1mm, wall thickness 0.10 ~ 0.15mm, one end fusion seal; when the thermometer used is immersed When the temperature transfer fluid is above 6cm, the length of the tube should be appropriately increased so that the exposed liquid surface is more than 3cm). Tap the wall of the tube or use a clean glass tube of suitable length to place it vertically on a watch glass or other suitable hard object. Put the capillary tube from the upper port to let it fall freely and repeat several times to make the powder tightly gather at the fusion-sealed end of the capillary tube. The height of the test article is 3mm. In addition, put the thermometer (sub-immersion type, with a scale of 0.5 ℃, corrected by the reference substance for the melting point measurement) into the temperature-transmitting liquid (the melting point is below 80 ℃, use water; the melting point is above 80 ℃, use silicone oil or liquid paraffin) In the container, make the distance between the bottom end of the mercury ball part of the thermometer and the bottom of the container more than 2.5cm (with a container heated internally, the distance between the mercury ball of the thermometer and the upper surface of the heater is more than 2.5cm); add the temperature transfer liquid to make the temperature transfer liquid The heated liquid level is suitable for the immersion line of the thermometer. When the temperature transfer fluid is heated and the temperature rises to about 10 ℃ lower than the lower limit of the specified melting point, immerse the capillary containing the test product in the temperature transfer fluid and attach it to the thermometer (can be fixed with a rubber ring or capillary clamp), The position must be such that the content of the capillary is suitable for the middle of the mercury ball of the thermometer; continue to heat, adjust the temperature increase rate to 1.0 to 1.5 ℃ per minute, and stir continuously to keep the temperature of the temperature transfer liquid uniform during heating, and record the test sample at the initial melting To the temperature at the time of full melting, repeat the measurement 3 times and take the average value to get it. Second method: Determination of solid medicines that are not easily crushed (such as fat, fatty acid, paraffin, lanolin, etc.). Take the test sample, pay attention to melting it at the lowest possible temperature, and suck it into the capillary tube open at both ends (same as the first method, but the tube end is not sealed), so that it is up to about 10mm. Let it stand for 24 hours in a cold place at or below 10 ° C, or let it stand on ice for not less than 2 hours. After solidification, use a rubber band to tightly bind the capillary to the thermometer (same as the first method), so that the content of the capillary The object part fits in the middle of the thermometer mercury ball. Immerse the capillary tube and thermometer in the heat transfer liquid according to the first method, and the upper end of the test sample should be about 10mm below the liquid surface of the heat transfer liquid; be careful to heat it up, so that the temperature rises to about 5 ℃ lower than the lower limit of the specified melting point When the temperature rise rate is adjusted so that the rise per minute does not exceed 0.5 ℃, until the test sample begins to rise in the capillary, check the temperature displayed on the thermometer to get it. The third method: determination of petrolatum or other similar substances. Take an appropriate amount of the test sample, slowly stir and heat to a temperature of 90-92 ° C, put it in a flat-bottom heat-resistant container, so that the thickness of the test sample reaches 12mm ± 1mm, and let it cool down to 8 ~ above the upper limit of the specified melting point 10 ℃; take a thermometer with a scale of 0.2 ℃, a mercury ball length of 18 to 28 mm, and a diameter of 5 to 6 mm (the upper part is pre-coated with a cork plug, and a small groove is opened at the edge of the plug), after cooling to 5 ℃, wipe dry and Carefully insert the mercury bulb of the thermometer vertically into the molten test sample until it touches the bottom of the container (submerged by 12mm), then take it out, hang it upright, and let the surface of the test sample adhering to the thermometer bulb become cloudy. Immerse it in water below 16 ℃ for 5 minutes, take it out, and then insert the thermometer into a test tube with an outer diameter of about 25mm and a length of 150mm, plug it tightly, hang the thermometer in it, and make the bottom end of the thermometer bulb about 15mm away from the bottom of the test tube ; Immerse the test tube in a water bath of about 16 ℃, adjust the height of the test tube so that the sub-immersion line on the thermometer is flush with the water surface; heat the temperature of the water bath to 38 ℃ at a rate of 2 ℃ per minute, and then at a rate of 1 ℃ per minute Increase the temperature until the first drop of the test product leaves the thermometer; check Temperature display on the meter, as an approximation to the melting point of the test. Take the test product again and repeat the measurement several times as before; if the difference between the melting points measured before and after 3 times does not exceed 1 ° C, the average value of 3 times can be taken as the melting point of the test product; if the difference between the measured melting points exceeds 3 times At 1 ℃, it can be measured twice, and the average value of 5 times is taken as the melting point of the test product. Cautions when operating the melting point determination method: "Initial melting" refers to the temperature at which the test sample begins to liquefy in the capillary when there are obvious droplets; "Full melting" refers to the temperature at which the test sample is fully liquefied. The method for measuring the test sample that melts and decomposes at the same time is as described above, but the temperature rise rate is adjusted to increase 2.5 to 3.0 ° C per minute; the temperature at which the test sample begins to liquefy (or when bubbles start to form) is used as the initial melting temperature; test The temperature at which the solid phase of the product disappears and all liquefies is taken as the full melting temperature. When the disappearance of the solid phase is not obvious, the temperature at which the decomposition product of the test product begins to expand and rise shall be taken as the full melting temperature. When some drugs cannot distinguish their initial melting and full melting, the temperature at which the mutation occurs can be used as the melting point.

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