Many official drugs contain varying amounts of water either in the form
of water of crystallisation i.e. hydrates or in absorbed form. Therefore
it is important to specify limits of water content in order to maintain
some sort to uniformity in these drugs.
Water content can be determined by any one of the following procedures: Loss on drying, for drugs containing no constituents other than water volatile at 105°C; Water content by Karl Fischer (Titrimetric) Mix and accurately weigh the substance to be tested, and, unless otherwise directed in the individual monograph, conduct the determination on 1 to 2 g. 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 to be employed in the determination. Put the test specimen in the bottle, replace the cover, and accurately weigh the bottle and the contents. By gentle, sidewise shaking, distribute the test specimen as evenly as practicable to a depth of about 5 mm generally, and not more than 10 mm in the case of bulky materials. Place the loaded bottle in the drying chamber, removing the stopper and leaving it also in the chamber. Dry the test specimen at the temperature and for the time specified in the monograph.[ NOTE — The temperature specified in the monograph is to be regarded as being within the range of ±2° of the stated figure. ] Upon opening the chamber, close the bottle promptly, and allow it to come to room temperature in a desiccator before weighing. 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. Water Content by Karl Fischer The most important method of determination of water content is the Karl Fischer electrometric titration method. It is widely applied for moisture determination of drug substances because it is very rapid, specific and requires very small amount of sample. The method consists of titration of sample in methanol in Karl Fischer reagent which incorporates iodine, sulpher dioxide, pyridine and methanol. The reactions involved are shown as: I2 + SO2 + H2O ® 2HI + SO3
SO3 + C5H5N ® C5H5N.SO3 (Pyridine-Sulfur-trioxide)
HI + C5H5N ® C5H5N.HI
C5H5N.SO3 + CH3OH ® C5H5N.HSO4CH3
Standardisation of Karl Fischer reagent Place sufficient quantity of methanol in the titration vessel and add sufficient amount of Karl Fischer reagent to give the characteristic end point. Weigh accurately 150-350 mg of sodium tartrate, (Na2C4H4O6,2H2O) accurately weighed, by difference and titrate to the end point. The water equivalence factor, F in mg of water per ml of the reagent is given by the expression 0.1566 w/v, where w is the weight, in mg, of the sodium tartrate and v is the volume, in ml, of the reagent required. The water equivalence factor F, in mgs of H2O per ml of reagent is calculated according to the formula 0.1566 x w/v, where W is the weight in mgs of sodium tartrate and V is the volume in ml of the reagent. Each mg of sodium tartrate is equivalent to:
2H2O 36.04------------------------ = ------------------- = 0.155 mg of H2O Na2C4H4O6,2H2O 230.08
Procedure Add 30 ml of methanol into titration flask. Neutralize with Karl Fischer Reagent to the electrometric end point. Refill burette. Weigh accurately specified qty of sample and transfer into a titration flask stir for 1 minute and titrate the solution with Karl Fischer reagent to the electrometric end point. Record the volume of Karl Fischer reagent consumed.
Calculation Formula: B.R. x F x 100 % Water (w/w) = ------------------------------- wt x 1000 Where, B.R. = Volume of Karl Fischer reagent consumed in ml. F = Karl Fischer Reagent factor in mg/ml. wt = Weigh of sample taken in g.
Also Read:Calibration of Karl fisher apparatusCalibration of automatic potentiometric titratorCalibration of ViscometerCalibration of UV CabinetCalibration of Analytical BalanceCalibration of melting point apparatusCalibration of FT-IR Spectrophotometer
Water content can be determined by any one of the following procedures: Loss on drying, for drugs containing no constituents other than water volatile at 105°C; Water content by Karl Fischer (Titrimetric) Mix and accurately weigh the substance to be tested, and, unless otherwise directed in the individual monograph, conduct the determination on 1 to 2 g. 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 to be employed in the determination. Put the test specimen in the bottle, replace the cover, and accurately weigh the bottle and the contents. By gentle, sidewise shaking, distribute the test specimen as evenly as practicable to a depth of about 5 mm generally, and not more than 10 mm in the case of bulky materials. Place the loaded bottle in the drying chamber, removing the stopper and leaving it also in the chamber. Dry the test specimen at the temperature and for the time specified in the monograph.[ NOTE — The temperature specified in the monograph is to be regarded as being within the range of ±2° of the stated figure. ] Upon opening the chamber, close the bottle promptly, and allow it to come to room temperature in a desiccator before weighing. 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. Water Content by Karl Fischer The most important method of determination of water content is the Karl Fischer electrometric titration method. It is widely applied for moisture determination of drug substances because it is very rapid, specific and requires very small amount of sample. The method consists of titration of sample in methanol in Karl Fischer reagent which incorporates iodine, sulpher dioxide, pyridine and methanol. The reactions involved are shown as: I2 + SO2 + H2O ® 2HI + SO3
SO3 + C5H5N ® C5H5N.SO3 (Pyridine-Sulfur-trioxide)
HI + C5H5N ® C5H5N.HI
C5H5N.SO3 + CH3OH ® C5H5N.HSO4CH3
Standardisation of Karl Fischer reagent Place sufficient quantity of methanol in the titration vessel and add sufficient amount of Karl Fischer reagent to give the characteristic end point. Weigh accurately 150-350 mg of sodium tartrate, (Na2C4H4O6,2H2O) accurately weighed, by difference and titrate to the end point. The water equivalence factor, F in mg of water per ml of the reagent is given by the expression 0.1566 w/v, where w is the weight, in mg, of the sodium tartrate and v is the volume, in ml, of the reagent required. The water equivalence factor F, in mgs of H2O per ml of reagent is calculated according to the formula 0.1566 x w/v, where W is the weight in mgs of sodium tartrate and V is the volume in ml of the reagent. Each mg of sodium tartrate is equivalent to:
2H2O 36.04------------------------ = ------------------- = 0.155 mg of H2O Na2C4H4O6,2H2O 230.08
Procedure Add 30 ml of methanol into titration flask. Neutralize with Karl Fischer Reagent to the electrometric end point. Refill burette. Weigh accurately specified qty of sample and transfer into a titration flask stir for 1 minute and titrate the solution with Karl Fischer reagent to the electrometric end point. Record the volume of Karl Fischer reagent consumed.
Calculation Formula: B.R. x F x 100 % Water (w/w) = ------------------------------- wt x 1000 Where, B.R. = Volume of Karl Fischer reagent consumed in ml. F = Karl Fischer Reagent factor in mg/ml. wt = Weigh of sample taken in g.
Also Read:Calibration of Karl fisher apparatusCalibration of automatic potentiometric titratorCalibration of ViscometerCalibration of UV CabinetCalibration of Analytical BalanceCalibration of melting point apparatusCalibration of FT-IR Spectrophotometer
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