Apparatus
The apparatus required is shown in Figure 1. The apparatus required is shown in Figure 1. It consists of a capillary metering valve, A, followed by a flow meter, B, to control and monitor the flow of nitrogen through the system. Halogenated vinyl plastic tubing and a rubber fitting, C, are used to connect the flow meter to a sidearm of a reaction flask, D. Flask D is a 250-ml round-bottom, boiling flask, resting in a suitable heating mantle, E. Flask D is provided with a 225-mm Hopkins coil reflux condenser, F. The condenser terminates in a U-shaped trap, G, which contain two 25-g bands of 20-mesh zinc, the bands being bounded and separated by three 3-inch plugs of glass wool. The trap terminates in an adapter, H, that by means of a halogenated vinyl plastic tubing and a twist cock connector, I, connects with a 250-ml gas washing bottle, J. The inlet (bubbling) tube extends almost to the bottom of the gas washing bottle, and it terminated in a fritted disk having a coarse porosity. The size of all glass joints is 24/40, except for the 45/50 joint of the gas washing bottle.
Figure 1. Apparatus
System suitability
Using D-glucuronolactone as the standard, proceed as directed for procedure, but do not perform the preboiling steps. Calculate the value for system suitability using the formula. The value for system suitability should be between 0.02 and 0.06.
Value for system suitability= CNaOHxVNaOH - CHCl xVblank
Where
CNaOH is the concentration of sodium hydroxide solution added, mol/l
VNaOH is the volume of sodium hydroxide solution pipetted, ml
CHCl is the concentration of hydrochloric acid, mol/l
Vblank is the volume of hydrochloric acid used for the titration of the blank, ml
Procedure
Weigh accurately about 0.25 g of the sample into the reaction flask, D. Add 50 ml of 0.1 mol/l hydrochloric acid, insert several boiling chips and connect the flask to the reflux condenser, F, using syrupy phosphoric acid as a lubricant.
Note: Stopcock grease may be used for the other connections.
Connect the nitrogen line to the sidearm of the flask, and adjust the flow of cooling water to about 2 l/min. Maintain the flow of nitrogen through the apparatus at 90 to 100 ml/min. Raise the heating mantle, E, to the flask, heat the sample to boiling and boil gently for 2 min. Turn the heat off, lower the mantle, E, and allow to cool for about 10 min. Connect the empty gas washing bottle assembly, J, and sweep the system with nitrogen at a rate of 90 to 100 ml/min for 5 min. Reduce the nitrogen flow to 60 to 65 ml/min, add 10 drops of 1-butanol, pipette 25.0 ml of 0.25 mol/l sodium hydroxide solution and add 50 ml of distilled water into the bottle, rinsing down the inside of the gas washing bottle, and replace the cap. Detach the rubber fitting, C, from sidearm, and add 46 ml of hydrochloric acid through the sidearm of the boiling flask. Reattach the nitrogen line, raise the heating mantle and heat the reaction mixture to boiling.
After 3 hours of boiling, increase the nitrogen flow to 90 to 100 ml/min, discontinue the heating and lower the mantle. Allow to cool for 10 min. Disconnect and disassemble the gas washing bottle. Using a directed stream of distilled water, thoroughly rinse all parts of the bubbling tube and cap, collecting the washings in the gas washing bottle. Use nitrogen to gently force all water out of the bubbling tube. To the bottle immediately add 10 ml of 10% barium chloride solution and a magnetic stirring bar. Insert a tight stopper and stir gently for 1 min. Allow to stand for at least 5 min. Add three drops of phenolphthalein TS and titrate with 0.1 mol/l hydrochloric acid. Perform a blank determination. Calculate the percentage of carbon dioxide from;
Where
CNaOH is the concentration of sodium hydroxide solution added, mol/l
VNaOH is the volume of sodium hydroxide solution pipetted, ml
CHCl is the concentration of hydrochloric acid, mol/l
Vsample is the volume of hydrochloric acid used for the titration of the sample, ml
LD is the loss on drying obtained, %
W is the weight of the sample, g
Each ml of 1 mol/l sodium hydroxide is equivalent to 22 mg of carbon dioxide.
1 Adapted from USP 37-NF32 with permission. Copyright 2013. The United States Pharmacopeia Convention
Apparatus
The apparatus used for the ethoxyl and methoxyl determination is shown in Figure 2. The boiling flask A, is fitted with a capillary side-arm, B, for the introduction of carbon dioxide and is connected to a column, C, which serves to separate aqueous hydriodic acid from the more volatile ethyl or methyl iodide. The volatile iodide passes through an aqueous red phosphorus suspension in a scrubber trap, D, and is finally absorbed in the bromine acetic acid solution in an absorption tube, F. The carbon dioxide is introduced from a device arranged to minimize pressure fluctuations and connected to the apparatus by a small capillary containing a small cotton plug.
Procedure
Prepare the apparatus by placing in trap D, through the funnel K or tube F and the connecting side-arm, a volume sufficient to make trap D half-full of a suspension of about 60 mg of red phosphorus in 100 ml of water. Rinse the tube F and the side-arm with water into trap D. Dry carefully the absorption tube F and pour down the funnel K 7 ml of bromine acetic acid TS. Weigh 0.05 g of the sample, to the nearest 0.1 mg, in a tared gelatin capsule, and place it in the boiling flask along with a few glass beads or pieces of porous plate. Add 6 ml of hydriodic acid TS and attach the flask to the condenser, using a few drops of the acid to seal the junction. Bubble carbon dioxide through the apparatus at the rate of about 2 bubbles per sec. Place the boiling flask in an oil bath heated to 150°, and continue the reaction for 40 min. Drain the contents of the absorption tube F into a 500 ml conical flask containing 10 ml of a 1 in 4 solution of sodium acetate. Rinse tube F with water, adding the rinsings to the flask, and finally dilute with water to about 125 ml. Add formic acid, dropwise, with swirling, until the reddish-brown colour of the bromine is discharged, then add 3 additional drops. A total of 12 to 15 drops are usually required. Let stand for 3 min, and add 15 ml of dilute sulfuric acid TS and 3 g of potassium iodide, and titrate immediately with 0.1 N sodium thiosulfate, using starch TS as indicator near the endpoint. Perform a blank determination, including also a gelatin capsule and make any necessary correction.
Each ml of 0.1 N sodium thiosulfate is equivalent to 0.517 mg of (-OCH3) or 0.751 mg of (-OC2H5).
Figure 2. Apparatus for determination of ethoxyl and methoxyl groups
Caution: Use a safety shield and conduct the distillation in a hood.
Principle
The oxyethylene groups are converted to ethylene and ethyl iodide which can be determined by titration. By utilizing a conversion factor determined on a reference sample, it is possible to compute the polyoxyethylene ester content.
Apparatus
An arrangement of apparatus for the analysis is shown in Figure 3. It consists in part of the reaction flasks (A), condenser, trap (B), and first absorption tube (C) of a Clark alkoxyl apparatus. These are followed by an absorption tube (D) made from a section of a spiral from a Widmer distillation column and a standard-taper (24/40) gas inlet adapter. Dimensions of the apparatus not readily determined from the diagram are as follows: carbon dioxide inlet, capillary, 1-mm inside diameter; flask A, 28-mm diameter, 12/18 standard-taper joint; condenser, 9-mm inside diameter; inlet to trap B, 2-mm inside diameter tube; inlet to trap C, 7/15 standard-taper joint, 2-mm inside diameter tube; trap C, 14-mm inside diameter; trap D, inner tube, 8-mm outside diameter, 2-mm opening at bottom of spiral; spiral, 1.75-mm rod, 23 turns, 8.5 rise per turn; trap D, outer tube, approximately 12.5-mm inside diameter, with side-arm 7 cm from top of spiral; side-arm, 3.5-mm inside diameter, 2 mm opening at bottom. The stopcock is lubricated with silicone grease. The absorption tubes may be conveniently suspended by a series of properly spaced sheet-metal clips attached to a stick clamped at an angle of about 60°.
Figure 3. Apparatus for determination of oxyethylene groups
Procedure
Fill trap B with a suspension of a small amount of red phosphorus in enough water to cover the inlet tube. Pipet 10 ml of acid silver nitrate TS into tube C, pipet 15 ml of bromine-bromide TS into tube D, and place 10 ml of a 10% potassium iodide solution in trap E. Place about 0.05 g of the sample, accurately weighed, in the reaction flask A, together with a Hengar boiling granule and 10 ml of hydriodic acid TS. Connect the flask to the apparatus, pass a slow stream of carbon dioxide through (about 1 bubble per sec), and heat the flask slowly in an oil bath to 140-145°.
Maintain the flask at this temperature for at least 40 min, until there is no longer any cloudy reflux in the condenser above the reaction flask, and until the supernatant liquid in the silver nitrate trap C has clarified almost completely. Five min before the completion of the reaction, heat the silver nitrate trap C to 50-60° in a hot water bath to drive out any dissolved olefin.
On completion of the decomposition, disconnect tubes D and C cautiously in that order. Then disconnect the carbon dioxide source and remove the oil bath from flask A. Connect the spiral absorption tube, D, by its lower adapter to a 500-ml iodine-titration flask containing 10 ml of 10% potassium iodide solution and 150 ml of water. Remove the potassium iodide tube, E, and rinse the side-arm into it. Allow the bromine solution to run into the titration flask through the stopcock and rinse the tube and spiral with a few ml of water. Add the contents of the potassium iodide tube to the titration flask, stopper and allow to stand 5 min. Add 5 ml of dilute sulfuric acid TS and titrate at once with 0.05 N sodium thiosulfate, using 2 ml of starch TS as indicator.
Rinse the contents of the silver nitrate trap C into a flask, dilute to 150 ml with water, heat to boiling, cool to room temperature, and titrate with 0.05 N ammonium thiocyanate, using 3 ml of ferric ammonium sulfate TS as indicator.
Perform a blank determination omitting the sample.
Calculation
The volumes of sodium thiosulfate solution (S ml) of normality N and ammonium thiocyanate solution (S' ml) of normality N' used to titrate the contents of the bromine and silver nitrate traps are subtracted from the corresponding blank titrations (B and B' ml, respectively) and the following calculations made:
The sum of the values obtained from these calculations represents the total oxyethylene content of the sample. The % of polyoxyethylene ester can be estimated from the ratio of the % of oxyethylene in the unknown sample to that in a reference sample of known purity.
