1021
INDUSTRIAL AND ENGINEERING CHEMISTRY
August 1947
CONCLUSIONS
LITERATURE CITED
For temperatures up t o 700' C. hydrogen was the most effihowcient of the reducing gases investigated. ~b~~~ 8000 ever, methane was quite reactive, perhaps as a result of Some thermal cracking of the gas a t these temperatures. Iron proved the most effective catalyst, in all reductions, although with hydrogen a t 650" C. 1% copper sulfat,e gave the same conversions as 0.4no iron.
c,,
ACKNOW LEI)C;.MEhT
TIle authors n-iskl to thank the B~~ chemical compaIly for finltncial aid and for supplying some of the materials used in this work.
(1) Budnikor, P. P., Compt. rend., 197, 60-3 (1933). (2) Budnikov, P. P., COmpt. rend. QCQd. SCi. U.R.S.S.. 1, 332-4 (1932). 208, 199-201 (1939). (3) Courtois, G., compt. (4) Dionisiev, D. E., J . Applied Chem. (U.S.S.R.), 9, 1386 (1936). ( 5 ) Kurtenacker, a., and Goldbach, E., Z . anorg. allgem. Chem.. 166, 177-8 (1927). (6) Ley, P., Chem.-Ztg., 58, 859-60 (1934). (7) Ley, P., and Teichmann, L., German Patent 666,987 (Dec. 24, 1932). (8) Nikrick, & I., I. and Kaaanskaya. Y., Trans. Inst. Chem. Chnrkov U&J., 4 , NO. 13, 149-55 (1938). (9) N. V. Stikstofbindingsindustrie "Nederland," German Patent 643,398 (April 6, 1937). White, J. F.&I,, and White, ~57.H,, cHEII., 28, 244-6 (1936) I
HYgroscopicity of Penicillin Salts CECIL CARR AND JOHN A. RIDDICK
Commercial Solvents Corporation, l e r r e Halite, lrtd.
D
URIIiG development work
011 the production of crystalline sodium penicillin, the crystalline salts \?-erefound t,o be more stable to heat and much less hygroscopic than the amorphous salts ( 2 ) . This study was undertaken to determine the humidity conditions necessary for miniinurn absorption of water when bulk lots of crystalline penicillin salts were processed. The several approximate relative humidities were maintained in dcsiccators containing saturated aqueous solutions of various salts in contact with a n excess of the solid phase. The humiditytemperature relations follow:
I.C.T. Data (.?) Solid P h a s e
t,
' C.
Humidity at 27-28' C .
Humidity, r:
(Estd.), 470 48 58
70 81
100
The estimated relative humidities a t the average temperature r m g e of t h e experiments were obtained as follows: Calcium nitrate was extrapolated from the 18.5-24.5' C. points, assuming a
401
c
I
I
straight-line function for the interval 18.5' to 28" C. The humidity for sodium bromide dihydrate is given at only one teniperature, 20' C., but similar salts do not show an :appreciable change in relative humidity with change in temperature \Tithin the range 20" to 30" C. The ammonium chloride-potassium nitrate value, was interpolated between the 25' and 30" C. values given III International Critical Tables ( 3 ) . The ammonium sulfate systcin does not vary b e b e e n 25' and 30" C.
T h e hygroscopicity has been determined for amorphous sodium and calcium penicillins and for crystalline sodium, potassium, and ammonium penicillins. The crystalline sodium salts are less hygroscopic than the amorphous salts. A relation, called the "critical humidity point," has been observed. This relation makes it possible I O determine the humidity control necessary for handling or storing bulk lots of penicillin in order to secure the mitiimum absorption of water.
d d
0
5
IO
DAYS I N
Figure 2.
15 20 HUMIDITY CHAMBER
25
Hygroscopicity of Amorphous Sodium Penicillin
30
35
INDUSTRIAL AND ENGINEERING CHEMISTRY
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Vol. 39, No. 8
40 I-
2
35
'
30
5
25
W
f 4
0
c
2o
z
W
v
15
W
n.
IO
5
5
0
DAYS
Figure 3.
I5
IO
0
DAYS
Hygroscopicity of Crystalline Potassium Penicillin
Figure 4.
C 30 I
2
3
z z4
25
20
0
15 20 25 I N HUMIDITY CHAMBER
30
35
Hygroscopicity of Amorphous Calcium Penicillin
The aiiiwphous hudium penicillin t ~ u obtained s in 200,000-unii vials and was from a regular plant run. The amorphous calcium penicillin and crystalline sodium, potassium, and ammonium penicillins \yere prepared in the laboratory. Subsequent chromatographic analyses indicated that approsimatcly 90% of the penicillin potency of the amorphous salts and over 90% of the potency of the crystalline salts was penicillin G. T h e assays of the various penicillin salts follow:
35
W
IO
5
IN HUMIDITY CHAMBER
I5
Biological Assay, @ / X g
I-
z w
10
U [L
w
5
Crystalline potassium penicillin
0
c
5 DAYS
Figure 5 .
0 701 '
6 o r @ -
I5
IO
20
IN HUMIDITY CHAMBER
r A
Hygroscopicity of Crystalline Ammonium Penicillin
I
CRYSTALLINE AMORPHOUS
I
hpproximately.0.5 gram of each of the crystalline salts was weighed into tared, ground-glass stoppered weighing bottles and dried overnight a t room temperature and 50 mm. pressure in a vacuum oven. The sodium and potassium salts were further
SODIUM
I
PENICILLIN
C R Y S T A L L I NE
SODIUM PENICILLIN
NU H IM MIBCEI R T YOF C HDAAr Y BSE RS A M P L E
WAS
IN
AMORPHOUS
e
C'RYSTALLINE
PO TA 5 S IUM CALCiUM
AMMONIUM
50
Figure 6.
Criticral Humidity Points of Penicillin Salts
P E N IC I L L l N
PENICILLIN
PENICILLIN
August 1947
INDUSTRIAL AND ENGINEERING CHEMISTRY
dried 8 hours a t 80" C. and 50 mm. pre-sure. T h e ammonium salt was not dried above room temperature because of its lolv h m t stability. The amorphous sodium and ealciuni salts were dried overnight a t 80" C. and 50 mm. pressure. The stoppers Ivere left out of the neighing bottles during the drying period aad replaced as soon as the bottles were removed from the oven. Tests in this laboratory indicate that the above method of drying gives substantially water-free material x h e n tested according to the mcthod set, forth by the Food and Drug .Idministration ( I ) , exrept that the ammonium salt may contain 0.1 to 0.2cp water. The weighing bottles were xeighed when cool and placed in the respective humidity desiccators n i t h t h e top out of the bottle. They were removed from the hunlidity chambers at intervals and weighed to drtermine the amount of moisture absorbed. The hygroscopicity data for a single salt species were plottcd as per cent gain in n-eight against time in the humidity chamber (Figures 1 to 5 ) . I t is apparent that potassiuni penicillin (Figure 3) is the least hygroscopic of the salts tested. The gain in rveight for 48, 58, and 70% humidities n-as less than O.-lnC at the end of 12 days. Cr)-stalline sodium penicillirl absorhed Ie?s than o.3cG nioisture at 48 and 58c;'0 humidities in 12 days. .in interesting characteristic was exhibited by animoniuni, calcium, and amorphous sodium salts. The dry salts absorbed 11-ater rapidly the first day to a limiting value and then remained a t a constant n-eight or absorbed much more slo~vly. The absorption at 1007, humidity for all thwe salts and a t 80% for the amorphous jotlium salts did not exhibit this characteristic. The absorption of a liniiting amount of water was not ail indication of hydrate iormation because the limiting amount of v-ntcr v a s incrcnscd with increased humidities. This is idpally exhibited by the calc % ~ salt m (Figure 4).
1023
The 100% humidity curves for the amorphous and crystalline salts shoived a marked difference in geueral slope. The slopes for the amorphous salts are much steeper than those of the crystalline salts, being alnlost perpendicular as plotted in Figures 2 and 4. When the percentage increase in \wight was plotted against the relative humidities for a given time period, ths increase in hygroscopicity with increasing humidity became apparent. -klI penicillin salts tested exhibited a decided break in this relation (Figure 6'1 a t one of the test humidities. The humidity a t which the slope of the curve increased appreciably has been called t,he "critical humidity point." Both sodium salts shoned a critical The other three salts !jho\ved this charhumidity point a t 705;. acteristic a t 81%. The differences between the humidity values studied are rather large. The critical humidity point as given represents the experimental humidity at which there is a decided change in the rate of absorption of moisture h v the salt. This point ma:; not represent the highest humidiiy at which this change occurs. Figure 6 points out clearly that crystalline sodium and potassium penicillins nmy be handled or storcd for at least 5 days in any space where the humidity is below the critical humidity point \I-irhout absorbing more than a, fraction of a per cent of 1r:tter. I t is not advisable to handle or stow, even for a short time, any of tlie penicillin salts a t R humidity above their critical humidity point because of the rapidity n i t h xhich they absorb nioisturt:. LITERATURE CITED
(1) Food and Drug Administration, Federal Register, p. 11483 (Sept 8 , 1945). (2) Hodge. Senkus. and Kiddick, Chem. Eng. News, 24. 21i7 (1846). ( 3 ) Spencer, International Critical Tables, s'ol. I, p. 67 (1926).
Effect of Dry Heat on Proteins J DALE IC. MECHAM AND HAROLD S. OLCOTT
V k s t e r n Regional Research Laboratory, tinited Strrtps D e p a r t m e n t of 4griculture, .4lbany, Calif.
1""
successful application of proteins t o iridastriul uses m a and Gersdorff (6) found no diflercrice b e t w e n the lysiiw contents require modification of the prot.eiiis Ijy simple physical or of hydrolyzates of heated and unheated casein. Stwgcrs and chrniical treatment. For example, Bruther, Binkley, and Brandon Mattill ( I S ) observed that beef liver suffered considerable loss in ( 7 ) report that chicken feathers and hoof meal, after bring heated iiutritive value as a protein source by being heated a t 120" for to 210-220" C. for 1 hour, can be u d adr:tntageously to modify 72 hours or by extiaction x-ith boiling &hano1 for 130 hourd; Balcelite-type molding plastics. The preient investigntion was but acid hydrolyzates of trested and untreated samples were undertalcen when it appeared that only a limited amount of insimilar in nutritive value. Harris and Mattill (11) found the formation as available concerning thi, chunges that occur in free amino nitrogen content of liver and kidney globulins to be proteins when they are suhjccted to dry heat. The data obdccreased (by half) by hot ethanol extraction. Sincc there was tainwl may assist in the modificatiori of proteins for .;u 1.pno loss in total nitrogen, they suggested that tlie dvcrense WLS t h r plirations as plastics, coatings, adlle;livc%s,and fibw5. result of the formation of new enzyme-resistan1 linkagcs involving 1 f o A t of the previous \\ 111.11 011 tile effect of heat L u ' < L i inent 011 proteins has Wheat gluten, casein, zein, egg w-hite, cattle hoof, arid soybean proiein w-ere heated bvt-11 rvportcd by investiin boiling inert hydrocarbons at temperatures from 110" to 203" C. for 18 hours. Solugstors intcrested in the bilitj decreased marhedly with increase of heating temperature up to l53", but there w a s no change in total nitrogen and little change in the amide nitrogen contents. niotlification oi iiutritive 4bove 1%' eutensiTe degradation occurred, with continuing loss of water and the pro~ivrties: tlic literature Lias heeii summarized by formation of more soluble products. With wheat gluten and zein, total and amide W:tisman a n d E l v e h j e m nitrogen contents were decreased. The amino and total basic groups of all ,*roteinswere ( 2 1 ) a n d hy G r e a v e s , found to be decreased b j the heat treatment. Wheat gluten and cattle hoof, after being llorgan, and Loveen ( I O ) . heated abobe 153", were not digestible by pancreatin. The cystine content of cattle hoof I>>-sine was reported to was markedly decreased by heat treatment above 153". Equilibrium moisture cnntenta at be the first amino acid iO% relative humidit? were decreased by heat treatment at all temperatures. The equilibrium moisture contents continued to decrease at temperatures above 153" dedamaged by heat treatrnrLnt ( I O ) , b u t Block, Jones, 3pite the increasing solubility of the heated products.
