Edition: BP 2025 (Ph. Eur. 11.6 update)
Dextran 70 Infusion
General Notices
Dextran 70 Injection, Dextran 70 Intravenous Infusion
Action and use
Plasma substitute.
DEFINITION
Dextran 70 Infusion is a sterile solution containing Dextran 70 for Injection, in Glucose Infusion or in Sodium Chloride Infusion. It is supplied as a ready-to-use solution.
The infusion complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of dextrans
5.5 to 6.5% w/v.
CHARACTERISTICS
An almost colourless, slightly viscous solution.
TESTS
Acidity
Titrate 25 mL with 0.01M sodium hydroxide VS using phenol red solution as indicator. Not more than 1.25 mL of 0.01M sodium hydroxide VS is required to neutralise the solution.
Molecular size
For solutions in Glucose Infusion, before proceeding with tests A, B and C add 4 volumes of ethanol (96%), centrifuge and dissolve the residue in sufficient Sodium Chloride Infusion to restore the original volume.
A. Determine the viscosities, Appendix V H, Method I, at 37°, using a U-tube viscometer (size C) of solutions in saline solution containing about 3.5, 2.5, 1.5 and 0.75% w/v of Dextrans, accurately determined. Calculate the viscosity ratio by dividing the time taken for the meniscus to fall from E to F using the liquid being examined by the time taken using saline solution. For each solution plot (viscosity ratio – 1.00)/concentration against concentration. The intercept on the viscosity ratio axis of a straight line through the points represents the intrinsic viscosity. The intrinsic viscosity is 0.22 to 0.27. B. Place 100 mL in each of five stoppered flasks and adjust the temperature to 24.9° to 25.1°. Maintaining this temperature, add slowly with continuous stirring sufficient absolute ethanol to produce a faint cloudiness (about 45 mL). To the separate flasks add 0.5, 1.0, 1.5, 2.0 and 2.5 mL of absolute ethanol, stopper the flasks and immerse in a water bath at about 35°, shaking occasionally, until clear solutions are obtained. Transfer the flasks to a water bath maintained at 24.9° to 25.1° and allow to stand overnight or until two clear liquid phases are formed. Discard the supernatant liquids, dissolve separately the syrupy residues in sufficient saline solution to produce 25.0 mL, remove the ethanol by evaporation at a pressure of 2 kPa, dilute to 25.0 mL with water and determine the optical rotation, Appendix V F. From the optical rotations calculate the amounts of dextrans precipitated as described in the Assay. Choose that fraction containing as nearly as possible but not more than 10% of the dextrans present in the infusion and determine its intrinsic viscosity by the method described under test A using a U-tube viscometer (size A). The intrinsic viscosity is not more than 0.36. C. Dilute the solution being examined with saline solution to contain 6% w/v of Dextrans. Place 100 mL in each of four stoppered flasks and add slowly, with continuous stirring, 80, 90, 100 and 110 mL respectively of absolute ethanol. Stopper the flasks, transfer to a water bath maintained at 24.9° to 25.1° and allow to stand overnight or until two clear liquid phases are formed. Separate the supernatant solutions from the syrupy residues. Remove the ethanol from each supernatant solution separately by evaporation at a pressure of 2 kPa, dialyse in cellophane tubing against water to remove sodium chloride, adjust the volume to 25.0 mL with water, add sufficient sodium chloride to produce solutions containing 0.9% w/v and determine the optical rotation, Appendix V F. From the optical rotations calculate the amounts of dextrans present as described in the Assay. Choose that fraction containing as nearly as possible but not more than 10% of the dextrans present in the infusion and determine the intrinsic viscosity by the method in test A. The intrinsic viscosity is not less than 0.13.
Content of glucose
For solutions in Glucose Infusion, 4.5 to 5.5% w/v, when determined by the following method. Dilute 15 mL to 50 mL with water. To 5 mL in a stoppered flask add 25 mL of a buffer solution containing 14.3% w/v of sodium carbonate and 4.0% w/v of potassium iodide and 25 mL of 0.05M iodine VS. Stopper the flask, allow to stand for exactly 30 minutes at 20°, add 35 mL of 2M hydrochloric acid and titrate immediately with 0.1M sodium thiosulfate VS. Repeat the operation using 5 mL of water and beginning at the words ‘add 25 mL…’. The difference between the titrations represents the amount of iodine required to oxidise the glucose. Each mL of 0.05M iodine VS is equivalent to 9.01 mg of glucose.
Bacterial endotoxins
The endotoxin limit concentration is 1.21 IU per mL, Appendix XIV C.
ASSAY
For solutions in Glucose Infusion
Add 0.05 mL of 5M ammonia to the required volume and measure the optical rotation, Appendix V F. Calculate the content of dextrans from the expression
0.5076(α– 0.528D)
where α is the observed angular rotation and D is the content of glucose as a percentage w/v determined in the test for Content of glucose.
For solutions in Sodium Chloride Infusion
Measure the optical rotation, Appendix V F, and multiply the value obtained by 0.5076.
STORAGE
Dextran 70 Infusion should not be exposed to undue fluctuations in temperature.
LABELLING
The strength is stated as the percentage w/v of dextrans. The label states (1) the name of the solvent; (2) that the infusion should not be used if it is cloudy or if a deposit is present.
