Evaluation of Polyvinylpyrrolidone Preparations GABOR B. LEVY, ISIDORO CALDAS, JR., AND DAVID FERGUS Schenley Laboratories, Znc., Lawrenceburg, Znd. The evaluation of new drug products, particularly those intended for intravenous applications, requires circumspect consideration, This was the case w-ith polyvinylpyrrolidone, which is being introduced to the United States as a plasma extender. The nature of the product required the investigation of two chemical tests-the determination of monomeric vinylpyrrolidone and of moisture, the only two compounds usually found admixed to polyvinylpyrrolidone. The physical chemical evaluation of the polymer presented a more complex problem, which was
P
studied in detail. A compromise was found so that relatively much information can be gained from a few simple operations and tests. The proposed method consists of the removal of inorganic salts, a two-cut fractionation of t h epolyvinylpyrrolidone solution, and determination of intrinsic viscosity of the solution and fractions. The method is not presented as a standard for acceptance but rather as a model procedure to be modified in accordance with clinical requirements. In this sense it may contribute to the evaluation of plasma extenders.
problems. For this reason, the authors felt compelled to choose relatively simple methods requiring a minimum of equipment. This is also the reason for describing the methods in detail below, even though some are routinely used in high polymer practice. The individual steps are presented and the reasons for the choice of methods are discussed separately in the following sections. Underlying the evaluation of polyvinylpj-rrolidone is the fact that its physiological properties are governed by its molecular weight. The molecular weight of any synthetic polymer is distributed over a certain range and a complete picture is obtained only if the distribution of the molecular weights is known. T o this end, the polymer has to be fractionated extensively and the individual molecular weights determined. I n the case of polyvinylpyrrolidone this process has been carried out repeatedly and the distribution of molecular n-eights has been determined (7). For this purpose larger batches of typical polyvinylpyrrolidone preparations were dissolved in water and consecutive fractions were obtained by the addition of acetone. These fractions were recovered and their molecular weight was determined by lightscattering measurements. A typical curve is shown in Figure 1. The variation in the character of these distributions of different batches is not too great. Therefore it was decided to limit the fractionation to the upper and lower fractions to gain an estimate of the breadth of the distribution of the individual batch. The additional determination of the average molecular weight serves to estimate the position of the distribution on the molecular weight scale. When theaverageof sucha distribution is discussed, the valuedepends on themethod 100 of summation and the corresponding method of de80 termining the average molecular weight. 9 In this connection, the 60 number average (obtained by osmotic pressure meas0 P urements) and the weight average (obtained by light40 U scattering measurements) 5 should be considered. The P PO latter has a higher numerical value and, depending on the distribution, may be twice thevalueof the former. The PO 40 60 80 100 viscosity average molecular MOLECULAR WEIGH1 (LIGHT SCATTERING) x 10-a weight (obtained by viscosity measurements) occupies Figure 1. Molecular Weight Distribution of Polyvinylpyrrolidone
OLYVINYLPYRROLIDOKE (PVP) is one of the products developed by Reppe (8, 14, 15) in his pioneering work in acetylene chemistry. I t is a water-soluble high polymer of many interesting properties (8). Some of these-viz., solubility, low toxicity, and physiological compatibility-made Hecht and Weese (9) utilize this compound as a plasma extender. The formulation of 3 to 4% polyvinylpyrrolidone in an isotonic aqueous solution, containing various inorganic salts, is usually employed, and such solutions have been used in Europe for several years with great success as plasma extenders. The use of polyvinylpyrrolidone preparations for this purpose is now under investigation in this country--e.g., PVP-hIacrose, Schenley-and the authors were confronted with the problem of evaluating these products. The complete testing of a drug product involves such determinations as toxicity, pyrogenicity, heavy metals, arsenic, and pH. Various standard tests are available ( I S ) . Only two methods of this type required home study-viz., the determination of moisture and of monomeric vinylpyrrolidone, the latter being a specific problem with the product in question. The use of a high polymer-Le., synthetic plastic-intravenously is not usual. Therefore a unique situation arose, of adapting techniques of high polymer chemistry to the evaluation of a drug product. The fact that the final form of the polymer is in a dilute saline solution, required special attention. Moreover, the degree of polymerization is relatively low and therefore some techniques are excluded. An additional consideration is that the uwrs of the product are rarely equipped to handle polymer
PO
16
k
X
s
x
u
z
w 3
8
B
a u
A
1?99
1800
ANALYTICAL CHEMISTRY
a position in between the two and is closer to the weight average, in some cases virtually coinciding. The interdependence of values of these averages was elucidated recently by Frank (6) and the experimental data relative to polyvinylpyrrolidone were presented by Frank and Levy (7). DETERMINATION OF RESIDUAL VINYLPYRROLIDONE
The determination of residual (monomeric) vinylpyrrolidone is
of some importance, as the toxicity of the monomer is appreciable. A characteristic of the monomer is the carbon-carbon double bond. It has been found that iodine reacts quantitatively with the monomer and this reaction is the basis of a determination. The reaction of iodine with polyvinylpyrrolidone does not interfere with this scheme because the polyvinylpyrrolidone complex is decomposed in the back-titration. Another suggested technique ( 1 ) consists of the treatment of aqueous solutions, containing the monomer, with sulfuric acid. This results in decomposition, yielding an equivalent amount of acetaldehyde. The aldehyde is then distilled and reacted with hydroxylamine hydrochloride. In consequence of the quantitative reaction of aldehyde and amine, an equivalent amount of hydrochloric acid is liberated and is determined volumetrically.
60
For the determination of polyvinylpyrrolidone content of solutions, the oven-drying procedure is to be used exclusively. This is particularly important when samples are recovered from organic solvents. In this case the oven drying will account for total solvent, whereas the Karl Fischer method accounts only for the water contained. DElMINERALIZATION OF POLYVINYLPYRROLIDONE SOLUTIONS
I t is necessary to remove the inorganic salts contained in the saline plasma extender in order to evaluate the component polyvinylpyrrolidone. After complete removal, the solution is an aqueous solution of polyvinylpyrrolidone (3 to 4%). Therefore all Eubsequent methods are equally applicable to a polyvinylpyrrolidone test solution (when a polyvinylpyrrolidone powder is tested) and to a demineralized plasma extender. The demineralization is carried out as follows: Prepare a bed of 20 grams of I R 120-H resin in a tube of 18mm. diameter. Rinse with distilled water. Introduce the polyvinylpyrrolidone solution with down flow at a rate of approximately 10 ml. per minute. Discard the first 50-ml. portion and collect additional 300 ml.
50
a >
DETERMINATION OF MOISTURE
In the case of solid polyvinylpyrrolidone powder, transfer 100 to 200 mg. into a tared serum bottle, seal immediately, and reweigh. Determine the water content in accordance with the Karl Fischer micromethod (11). As an alternative procedure, dry the sample to constant weight in an oven a t 105’ C. or in a vacuum oven a t Ion-er temperatures. If the temperature of drying exceeds 50’ C., the samples should not be used for any subsequent work, since their physical characteristics-e.g., solubility-may be changed. In these cases the oven drying is merely an analytical technique to calculate the dry weight of the samples used for physical testing.
40
1345
k 30
PO IO 1340
0.1
0.9
Figure 2.
0.3 0.4 0.5 INTRINSIC VISCOSITY
0.6
0.1 ‘,4
Relation of K Value and Intrinsic Viscosity 1335
The authors’ tests have shown that the second method yields the more accurate and reproducible results.
Apparatus. A 250-ml. round-bottomed flask with a f 24/40 joint carrying a 60-cm. Allihn condenser is used. The upper joint of the condenser is connected by a C-shaped f 24/40 adapter to another 60-cm. Allihn condenser. At the lower end of the descending condenser is placed a 250-ml. Erlenmeyer flask suspended in an ice bath. Reagents. Approximately 257, sulfuric acid, C.P. Approximately 1N hydroxylamine hydrochloride solution. 0.1 N sodium hydroxide solution. Bromophenol blue indicator solution. Procedure. Transfer about 30 grams of polyvinylpyrrolidone (weighed to the nearest milligram) and 100 ml. of vvater, or a corresponding solution, into the flask and add 20 ml. of 25% SUIfuric acid. Reflux the mixture for about 30 minutes. In the meantime, transfer 25 ml. of hydroxylamine solution into the receiver and determine on another aliquot the “blank” value by titration with 0.1 N sodium hydroxide and bromophenol blue a8 indicator. After the refluxing, disconnect the water supply of the ascending condenser and distill 60 ml. into the receiver. Titrate the contents of the receiver with 0.1 N sodium hydroxide and calculate the amount of monomer:
MI.of NaOH - ml. of NaOH (blank) X Y sample weight
11.12 = % monomer
1330
I
I
P
4
6
PER CENT P V P
Figure 3.
Refractive Index of Polyvinylpyrrolidone Solutions i n Water
Transfer this fraction into a beaker and add 30 grams of I R 4 B resin. Stir until pH 5.0 is reached. Filter and check ash content of the filtrate; it should not exceed 0.02%. DETERMINATION OF INTRINSIC VISCOSITY
In order to determine the average molecular weight of polyvinylpyrrolidone and the molecular weight of its fractions, various methods can be used, as discussed above. Because osmotic phenomena are involved in the use of polyvinylpyrrolidone as a plasma extender, one might be inclined to use osmotic pressure measurements and, correspondingly, obtain number average molecular weights. The authors have studied this method ex-
V O L U M E 24, NO. 1 1 , N O V E M B E R 1 9 5 2
1801
will permit interconversion of these two data derived from vistensively and concluded that, because of the relatively low degree cosity measurements. of polymerization, it is impossible to use this technique for the Since the determination of intrinsic viscosity is basic in all exusual polyvinylpyrrolidone preparations and the low molecular perimental work, some care was taken to investigate its applicaweight fractions. Others seem t o concur in this conclusion ( 4 , 1 6 ) . bility. The temperature coefficient was determined-e.g., for a Furthermore, when high molecular weight fractions are tested, sample showing an intrinsic viscosity of 0.207 a t 16.9" C., the the values are uncertain, because of adsorption phenomena on the values a t 25.0', 31.0', and 37.2' C. are 0.186, 0.175, and 0.167. membranes, unless extreme precautions are taken. Moreover, in Therefore the temperature of the viscosity determination should the body the membrane equilibria are so complex that the be fixed reproducibly to only about '1 C. On the other hand, analogy is remote between those and the osmotic pressure measfluctuations during the determination should not exceed 0.1' C., urements with cellulose membranes in pure solutions of polyvinylpyrrolidone. Another method usually employed in polymer chemistry for the determination of molecular weights is that of light-scattering. This method was found to be suitable for polyvinylpyrrolidone in methanolic solutions. However, it required the evaporation and complete drying of the aqueous solutions to be tested. The equipment necessary is intricate and expensive and the determination timeconsuming. As an alternative method, the determination of intrinsic viscosity is much preferred. The equipment is simple and the determination rapid without requiring exceptional skill. However, the results are relative rather than absolute and another method for the determination of molecular weight is needed to establish the relationship between intrinsic viscosity and molecular weight. The correlation between intrinsic viscosity and weight average molecular weight has been established ( 7 ) and therefore the intrinsic viscosity data can be readily converted into molecular weight figures. However, this is not absolutely necessary in control work when batches can be compared directly by intrinsic viscosity figures. The use of viscosity as an index of the molecular weight of polyvinylpyrrolidone is rather generally accepted. Most foreign workers express the viscosity data according to the K function ( 5 ) rather than by intrinsic viscosity, [q]. The K function is derived from the relative viscosity: log qrel. = (75K!/( 1 1.5Kc) Kc, mThere K X 1000 = K value. The authors have found that polyvinylpyrrolidone does not follow the K function over an extended range of concentration. Xevertheless, the K values may serve as an approximation. I n Table I are given the K values corresponding t o the relative viscosity 1 P 3 4 5 6 7 8 values a t 1 gram per 100 ml. In Figure 2 is given the reVOLUME RATIO OF SOLVENT TO WATER lationship between K value and intrinsic viscosity based 'igure 4. Precipitation of Polyvinylpyrrolidone from Aqueous on the equation: [q] = 2.303 (75K2 K ) ( I d ) . This Solution
+
+
+
Table I.
K Values
Reduced Viscosity (at 1G./100 Ml.)
K Vdue
Reduced Viscosity (at 1G./100 hll.)
K Value
0.11 0.12 0.13 0.14 0.15 0.16 0.17 0.18 0.19 0.20 0.21 0.22 0.23 0.24 0.25 0.26 0.27 0.28 0.29 0.30
19.0 20.0 21.0 22.0 22.9 23.7 24.6 25.4 26.2 26.9 27.7 28.4 29.0 29.7 30.4 31.1 31.7 32.4 33.0 33.6
0.38 0.39 0.40 0.41 0.42 0.43 0.44 0.45 0.46 0.47 0.48 0.49 0.50
37.9 38.4 38.9 39.4 39.9 40.3 40.8 41.3 41.7 42.1 42.6 43.1 43.5
since larger variations, while determining the viscosity of the solvent and that of the sample, will cause a serious error. The effect of various salts was found to be large, as reported by Jirgensons (IO). Therefore, salt solutions as solvent are not recommended. Moreover, the use of buffers is not necessary, as the authors found that the intrinsic viscosity of several polyvinylpyrrolidone preparations was unaffected by changes in p H between 3.0 and 7.0. Organic solvents have a large effect and, when used for precipitation of polyvinylpyrrolidone, they should be removed so that their concentration does not exceed 1 %. The determination of the intrinsic viscosity is carried out as follows: On the basis of the solids determination adjust all solutions so that they fall in a range of 1.5 to 2.0 grams per 100 ml. For a rapid estimation determine the refractive index and use Figure 3. (The use of the refractive index for this estimation is possible because the refractive index is independent of the molecular weight within the range used, as was verified experimentally.) Filter the solution using a fritted glass filter of medium porosity until the solution is completely free of lint. Transfer 10 ml. into an Ubbelohde viscometer which is suspended in a vertical position in a water bath a t 25" j=0.1" C. The viscometer should have an emus time for water between 50 and 100 seconds per ml. The water
1802
ANALYTICAL CHEMISTRY
value is to be determined daily and should not deviate more than 0.3 second. (The preferred technique for cleaning the viscometer, to maintain this constancy, consists of soaking overnight in cleaning solution, rinsing with water followed by 30 minutes' soaking, rinsing with methanol, and drying.) Determine the efflux time of the polyvinylpyrrolidone solution and subsequently make 3 dilutions by adding 3, 3, and 9 ml. of distilled mater. Other convenient dilutions may be chosen. After each dilution mix thoroughly by bubbling air through the reservoir. For each dilution obtain three replicate efflux times which do not vary by more than 0.3 second (excessive scatter indicates uncleanliness or the presence of lint). 40
30
B
7c P
8 PO c
a P
& W
10
0.3
0.4 0.5 INTRINSIC VISCOSITY
0.6
Figure 5. Dependence of Intrinsic Viscosity on Quantity Precipitated in High Molecular Weight Fraction
Calculate the relative viscosity for each dilution by dividing the average efflux time by that of water. Subtract 1 from the relative viscosity and divide these values by the corresponding values of rlyvinylpyrrolidone concentration to obtain reduced viscosity. lot reduced-viscosity values against concentration and read off intrinsic viscosity a t zero concentration. (To determine the K value read off the reduced viscosity corresponding to a concentration of 1 gram per 100 ml. and use Table I.) FRACTIONATION OF POLYVINYLPYRROLIDONE
The fractionation of polymers is a well established procedure and considerable information is available on the solubility of polyvinylpyrrolidone of different molecular weights in various solvent systems (2). Hovi-ever, aqueous systems were considered only because the direct utilization of the demineralized aqueous solutions is most expedient. In this manner, the addition of acetone to aqueous solutions of polyvinylpyrrolidone has bren used extensively (1, 3, 4,10, 16) and this causes a gradual precipitation (in liquid phases) of the higher molecular weight fractions. The upper curve in Figure 4 shows the course of precipitation of the acetonewater system with a typical polyvinylpyrrolidone preparation. As evident, there is a narrow margin of acetone addition which causes almost complete precipitation of polyvinyipyrrolidone. On incorporation of 10% (by volume) of isopropyl alcohol in acetone, a flatter curve results (lower curve of Figure 4). This has two advantages: The control of the amount precipitated is facilitated, and because of the lesser precipitating action, sharper discrimination of molecular weights is achieved. In this manner, the quantity or percentage of the fraction precipitated can be controlled within a narrow limit, if the conditions are properly controlled. Nevertheless, a scatter of a few per cent is inevitable and this renders comparison between samples difficult. By studying the Course of the precipitation, it nap found
that the slope of the curves [ q ] us per cent precipitated Rith different preparations is similar (Figure 5). On this basis, it is possible to make a rough estimation of the intrinsic viscosity a t any given percentage. Taking the 10% fractionation level, the slope approximates 0.005 intrinsic viscosity units per per cent. Using this factor, all precipitations around 10% may be reduced to that level-e.g., if the actual amount precipitated nas 11%, 0.005 is added to the intrinsic viscosity found for that fraction. This corrected value will be in close agreement nith the intrinsic viscosity of a fraction of 10%. A similar situation exists in the lorn molecular weight fraction. The corresponding correction is 0.004 intrinsic viscosity units per per cent and it is to be applied Kith the opposite sign, the correction being added n-hen the fraction is less than 10%. These corrections represent average figures centering around 10% precipitation level and should be applied only as approximations. The conditions of the precipitation will govern the amount precipitated, as mentioned above. The authors have chosen 28" C as a temperature standard for all operations because it is easy to maintain in all seasons. The concentration of the aqueous solution was chosen a t 3.5% polyvinylpj-rrolidone content because it is the lowest concentration usuallv employed in plasma extenders. Moreover, it is lox enough to obtain satisfactory separation by molecular weight (this is not true at higher concentrations-e.g.. a 10% solution cannot be resolved satisfactorily by the acetonewater system). Under these conditions, a specified amount of precipitant will precipitate a predetermined percentage of the material, depending on the molecular weight distribution. Below are given the volumes which will separate a 10% upper and 9 10% lower molecular weight fraction from a usual polyvinylpyrrolidone preparation of an intrinsic viscosity of about 0.21. If the starting material is different or if the fractions are to represent different proportions, the volume of the precipitant has to be adjusted accordingly. The 10% cuts are recommended as a reasonable compromise. If the cuts are substantially larger, their value diminishes in assessing the breadth of the distribution, and if very large they will not differ much from the average valuei.e., intrinsic viscosity of the original sample. If the cuts are much smaller than IO%, there will not be enough material for subsequent testing unless a very large amount of polyvinylpyrrolidone is subjected to fractionation. Low Molecular Weight Fraction. Transfer 200 ml. of polyvinylpyrrolidone solution (either demineralized plasma extender or a 3.57, solution of polyvinylpyrrolidone in distilled water) into a closed vessel (separatory funnel, flask, or the like) and add 6 volumes of acetone. Mix the solutions thoroughly by stirring or by frequent shaking. After 18 minutes allow phases to separate a t 25" & 0.1" C. The separation \?ill require a t least 6 hours. It is preferable to allow overnight settling. Syphon the upper layer sharply and transfer into a flask connected to vacuum. Evaporate the solvent until the volume is reduced to a few milliliters, transfer the contents of the flask into a 25-ml. volumetric flask, using distilled water, and make up to volume. Determine solids concnt and intrinsic viscosity. High Molecular Weight Fraction. Csing an identical techniaue. treat another 100-ml. aliauot ivith 3.5 volumes of acetone coitaining 10% by volume of isopropyl alcohol. Treat eLactly as low molecular weight fraction, with the exception that the lower layer is to be recovered in this case. DlSCUSSIOh A h D RESULTS
In setting up specifications for polj-vinylpyrrolidone and plasma extenders based on polyvinylpyrrolidone, the usual tests for purity (USP XIV) should be used ( f Y ) , keeping in mind that 500 ml. are usually employed as a dose, representing 15 to 20 grams of polyvinylpyrrolidone. The monomeric vinylpyrrolidone content should also be specified because of its relative toxicity. With respect to the molecular might, the range of average intrinsic viscosity (or K value) should be given. I n addition, the upper and lower 10% of the material should fall wibhin certain limits of intrinsic viscosity (or corresponding K value). .4ny specifications are dependent to some extent on the tech-
V O L U M E 24, NO. 11, N O V E M B E R 1 9 5 2 Table 11.
Replicate Physical Tests of PVP Samples Fractions High Molecular Weight Low Alolecular Weight Fractionated, Fractionated,
[?I
Code
%
[ri 1
10.3 7.4 12.1 8.3 11.5 9.6 10.8 13.0 12.4 13.8 12.2 15.3 13.1 12.5 13.4 14.6 13.8 11.9 11.6 7.6 5,7
0.393 0.423 0,445 0.487 0,583 0.573 0,572 0.447 0.427 0.422 0.417 0.392 0.414 0.365 0.374 0.367 0.387 0.388 0.395 0.383 0.394
9.2 16.8 10.6 21.1
0.063 0.107 0.058 0.110 0.079 0.093 0.093 0.083 0,098
14.6 15.0 9.2 9.8 8.5 12.3
0.074 0,072 0.053 0.052 0.053 0.080
20.6 11.0
0.386 0.423
..
. ..
%
1
0.213
2
0.203
3
0.213
4
0.222
32/50
0,227
33/50
0.210
390208
0.210
101
0.185
102
0.213
0 231
103
1803
Deriiineraliaed plasma extender G Ill 0.197 G 108 0,198
[7
1
10 3
23.1 23.9 8.4 15.9
..
,
..
r r o m PVP 0.209 Dernineralized‘plasma extender G 112 0 186
10 6
0 413
..
...
15.1
From PVP
14.6
0.343 0.367
13.4 9.8
0 065 0.052
0.183
nique of separation. Rrfractionation ~ o u l dtend to improve the purity of the fractions, but is usually not necessary for a control method. The preparation of more fractions than the proposed two m-odd give a better picture of the molecular w i g h t distribution. However, the information gained is disproportionately small. The proposed method of evaluation of polyvinylpyrrolidone plasma extenders is PO designed that all of the analytical work is done on the product directly. The solution is demineralized, its intrinsic viscosity i F determined, t n o fractions are srparated
simultaneously, and their intrinsic viscosity is determined. Throughout, only small samples are dried to determine the solids content of the various solutions. The individual st’epsare simple and require a minimum of equipment. S s proposed, polyvinylpyrrolidone preparations can be sufficiently characterized for all practical purposes and the results obtained within 24 hours’ t h e . I n Table I1 are shown a number of replicate analyses which were taken a t random and serve to indicate the reproduciblity of the results by the proposed physical techniques. The last sets of results are presented to indicate the efficiency of the demineralization procedure. ACKNOWLEDGMENT
The technical assistance of Mrs. Elsie Schneider is gratefully acknowledged. The authors thank Kurt Ladenburg and Bruno Puetzer for discussions and encouragement and Schenley Laboratories, Inc., for permission to publish this material. LITERATURE CITED
(1) Badische Anilin- und Soda Fabrik, private communication. (2) Copenhaver, J. W., and Bigelow, Wf. H., “Acetylene and Carbon Monoxide Chemistry,” New York, Reinhold Publishing Corp., 1949. (3) Dialer, K., and Vogler, K., Makromol. Chem., 6, 191 (1951). (4) Eirich, F. R., private communication. (5) Fikentscher, H., Celluhechemie, 13,58 (1932). (6) Frank, H. P., J . Polymer Sci., 7, 567 (1951). (7) Frank, H. P., and Levy, G. B., Ibid. (in press). (8) General Aniline & Film Corp., S e w York, “PVP, An Annotated Bibliography,” 1951. (9) Hecht, G., and Weese, H., Mii~zch. med. Wochschr., 90, 11 (1943). (10) Jirgensons, B., Makromol. Chem., 6, 30 (1951). (11) Levy, G. B., Murtaugh, J. J., and Rosenhlatt, M.,IND. ENQ. C R E X . , -4NAL. ED.,17, 193 (1945). (12) Matthes, A., Angew. Chem., 54, 517 (1941). (13) Pharmacopeia of the Cnited States of America, 14th revision ( U P XIV), Easton, Pa., Mack Publishing Co., 1950. (14) Reppe, W., “Chemie und Technik der Acetylen-Druck-Reaktionen,” Weinheim, Verlag Chemie, 1951. (15) Reppe, IT., “Neue Entwicklungen auf dem Gehiete der Chemie des Acetylens und Kohlenoxyde,” Berlin, Springer Verlag, 1949. (16) Scholtan, W., private communication. RECEIVED for review November 12, 1951. Accepted July 25, 1952.
Reduction by Aluminum Powder in Aqueous Solution Volumetric Determination of Iron E. RAYMOND RIEGELI
AND ROBERT
D. SCHWARTZZ, University of Buflalo, B u g a h , N. Y
C
OMPARATIVELY little has been reported on the use of aluminum as a reducing agent in aqueous solution. The authors plan t o study the reducing action of aluminum by means of reactions with several oxidants [iron(III), vanadium(V), molybdenum(VI), tungsten(V1)l. These oxidants Rere chosen to include substances which are sometimes reduced by metals in volumetric analysis. One of the aims of this work is the establishment of volumetric determinations based upon reduction by aluminum, and subsequent titration with a standard solution of an oxidant. This paper covers the first determination studied which was that of iron. PREVIOUS WORK
A search of the literature on the reduction of iron(II1) by aluminum yielded the following information. Carnegie ( 2 ) 1 2
Present address, R.D. 91, Deep River, Conn. Present address, 53 Groveland Ave., Buffalo 14, N. Y .
studied the action of finely divided aluminum on solutions of iron(111) salts and mentioned that aluminum reduced most slowly of all the metals experimented with. Fritchle (4)used strips of aluminum to reduce iron(II1) in dilute sulfuric acid solution. Seamon (12) recommended the use of sheet aluminum for the same purpose and noted that hydrochloric acid, in small amounts, speeded the action. At about the same time, Carulla ( 3 ) advocated using aluminum as a substitute for zinc in reductions of iron(II1). The reaction between iron( 111) and aluminum was used by Kohn-Abrest (8) t o determine the metallic aluminum content of aluminum powder. Schumann (11) used a chain of heavy aluminum wire t o perform iron determinations and mentioned the use of an aluminum wire spiral by Campbell (I). Furman ( 5 ) refers to certain errors in the method of KohnAbrest (8) and does not advocate its use. Recently, Light and Russell (10) proposed modifications of the method of KohnAbrest for determining the metal content of aluminum pigments.
