LITHIUM CARBONATE

Henry C. Stober

1. Description
1.1 Name, Formula, Molecular Weight
1.2 Appearance, Color, Odor
1.3 Drug Properties

2. Physical Properties
2.1 Infra-red Spectroscopy
2.2 Raman spectroscopy
2.3 Atomic Emission and Absorption Spectroscopy
2.4 Melting Point
2.5 Thermogravimetric Analysis
2.6 Dissociation Constant
2.7 Conductivity
2.8 Microscopy
2.9 Index of Refraction
2.10 Density
2 . 1 1 Crystal Structure
2.12 X-Ray Powder Diffraction
2.13 Polymorphism
2.14 Solubility
2.15 Dissolution

3. Preparation of Lithium Carbonate

4. Stability
4.1 Solution
4.2 Solid State (Light, Thermal, Humidity)

5. Methods of Analysis
5.1 Identification Test for Lithium
5.2 Identification Test for Carbonate
5.3 Microchemical Test for Lithium
5.4 Microchemical Test for Carbonate
5.5 Volumetric Analysis
5.6 Atomic Emission and Absorption Spectroscopy
5.7 Other Spectrometric Techniques
5.8 Conductivity
5.9 Ion Selective Electrodes
5.10 Ion Chromatography

6. Medicinal History

7. Pharmacology
ANALYTICAL PROFII.ES OF DRUG SUBSTANCES Copyriglit Q 1986
VOLUME 15 hy the American Pharmaceutical Association
367 All rights o!' reproduction i i i any form reserved.
368 HENRY C.STOBER

LITHIUM CARBONATE

1. Description

1.1 Name, Formula, Molecular Weight

Chemical Name
Lithium Carbonate

Nomenclature
The following nomenclature is used in Chemical
Abstracts: Carbonic Acid, Dilithium Salt
[ 554-13-21

Trademarks
The following trademarks are listed in the Merck
Index (1): Camcolit; Candamide; Carbolith;
Ceglution; Eskalith; Hypnorex; Lithane; Lithobid;
Lithonate; Lithotabs; Plenur; Priadel; Quilonum
retard.

Molecular Formula and Weight (1)

Li2CO3 73.89
C: 16.25% Li: 18.78% 0: 6 4 . 9 6 %

1.2 Appearance, Color, Odor

White, granular, odorless, light alkaline powder
(1,2) *
1.3 Drug Properties
Lithium Carbonate, by virtue of the therapeutic
properties of lithium, is used for the treatment
of manic depressive psychoses. The drug is
listed in the United States Pharmacopea (21, the
British Pharmacopoeia (3)) and the Modern Drug En-
cyclopedia (4), as well as Remington's Pharmaceu-
tical Sciences (5).

2. Physical Properties

2.1 Infra-red Spectroscopy

The infra-red spectrum of lithium carbonate
dispersed in KBr is shown in Figure 1 (6).
Literature sources have demonstrated that the
infra-red spectrum of lithium carbonate is
consistent with its known crystal structure ( 7 ,
8). The infra-red spectrum of lithium carbonate
 n
d
I
E
UI
n U
W
0
0
03
0
0
0
rl
0
0
hl
rl
0
0
-3
4
0
3
\D
rl
0
0
c3
rl
0
0
0
hl
0
0
Ln
N
3
3
3
m
3
3
n
m
370 HENRY C.STOBER

has also been obtained as a film on sodium

chloride plate and as Vaseline and flurolub
suspensions ( 7 , 9 ) . A summary of the character-
istic infra-red bands for lithium carbonate is
presented in Table I.

TABLE I

Characteristic Infra-red Bands of Lithium Carbonate (7)

Frequency (cm-l) Wavelength (p) Relative Intensity

2558 3.91 W
2494 4.01 W
1842 5.43 W
1806 5.54 W
1495 6.69 vs
1437 6.96 vs
1088 9.19 M
866 11.55 S
846 11.82 W
741 13.50 W
7 12 14.04 vw

The infra-red absorption band at 1088 cm-l can be

used to uniquely quantitate lithium carbonate in
the presence of other alkali carbonates ( 1 0 ) .
The observed frequencies related to the isotopic
species 6LizC03 and 'Li~C03 have been reported by
Tarte ( 1 1 ) .

2.2 Raman Spectroscopy

The Raman spectra of crystalline and molten
lithium carbonate have been reported by Brooker
and co-workers ( 1 2 , 1 3 ) . Major bands are ob-
served at 1091 and 1459 cm-l.

2.3 Atomic Emission and Absorption Spectroscopy

Lithium carbonate can be made to exhibit the
characteristic emission spectrum of lithium.
Three typical analytical emission lines are
obtained for lithium containing aqueous solu-
tions. These are summarized along with their
relative intensities in Table I1 ( 1 4 ) .
LITHIUM CARBONATE 371

The line at 670.8 nm is particularly intense and

imparts a deep red color to an oxidizing flame.

TABLE I1

Lithium Analytical Emission Lines

Wavelength (nm) Relative Intensit9

670.8 1
323.3 235
610.4 3600

+'relative amount of lithium required for 1%

response

Typical sources of excitation include

air-acetylene and nitrous oxide-acetylene flames.
More recently electrothermal and argon plasma
excitation techniques have become available.
Because of its greater sensitivity the line at
670.8 nm is most often used for the analysis of
lithium by flame emission spectroscopy, atomic
absorption spectroscopy and plasma spectros-
copy (14, 15).

2.4 Melting Point

The melting behavior of lithium carbonate has
been evaluated by DTA using both heating and
cooling programs. Lithium carbonate has been
reported by various sources to melt in the
temperature range of 714O to 733OC (16-25) depend-
ing on the atmosphere employed (ie. C02 or air)
and the degree of dissociation of Li2CO3 to Liz0
and C02 that occurs as the melting point is
approached (16, 18, 20, 21).

Typical thermal properties reported in the

literature for lithium carbonate are summarized
in Table 111.
372 HENRY C. STOBER

TABLE I11

Thermal Properties of Lithium Carbonate

Melting Point (23) 993OK; 72OOC

Heat Capacity (23) 23.2 cal/mole /deg
Specific Heat (24) 0.315 cal/g
Heat of Fusion (24) 10.7 kcal/mole

2.5 Thermogravimetric Analysis

Data obtained for a typical lot of lithium
carbonate (H2O < 0.5%)- by thermogravimetric
analysis is presented in Table IV. Under the
conditions employed the compound is essentially
weight stable up to 200OC with only water loss.
Above 200OC a gradual continuing weight loss is
observed. This behavior is consistant with that
reported by Machaladze and co-workers (21).

TABLE IV

Lithium Carbonate: Thermogravimetric Behavior (26)

TGA (N2 atmosphere) Perkin-Elmer TGS-1

Scan rate 10°C/minute

RT to 90°C 0.11% weight loss

900 to 200oc 0.08% weight loss
ZOOo to 45OOC 0.63% weight loss
above 45OOC continuing weight loss

2.6 Dissociation Constant

The pKa's for the first and second ionization
steps of the conjugate acid of the carbonate ion
are reported in the literature to be 6.38 and
10.25 respectively (27).
LITHIUM CARBONATE 373

2.7 Conductivity
The relationship between the equivalent conduc-
tance (4) and the concentration of lithium
carbonate is typical of a strong electrolyte. A
plot of& versus JC yields straight line for
concentrations less than 0.01N. The equivalent
conductance at infinite dilution (4')for lithium
carbonate was determined to be 110.2 R/cm2/Eq
at approximately 25OC, from this plot (6).

2.8 Microscopy
USP Lithium Carbonate is a microcrystalline solid
that is birefringent under crossed polars. The
solid has been observed to exist as polycrystal-
line aggregates ranging from approximately 10 to
85 micrometers in diameter (6).

2.9 Index of Refraction (ND25)

The refractive indices of Lithium Carbonate have
been reported as 1.428, 1.567 and 1.572 (25).
Lithium Carbonate is biaxial and is optically
negative.

2.10 Density
The density reported for Lithium Carbonate is
2.11 g/cc 125):

2.11 Crystal Structure

The crystal structure of Lithium Carbonate is
monoclinic w'th unit cel dimensions of a = 8.39
k,
A, b = 5.00 c = 6.21 , and f3 = 114.5+ (28).
The crystal lattice belongs to the space group
Cg - C 2/C and there are four lithium carbonate
mofecules per unit cell (29, 7).

2.12 X-Ray Powder Diffraction

Major lines present in the x-ray powder diffrac-
tion pattern of USP grade lithium carbonate are
presented in Table V. Strong lines are observed
at 31.6, 21.4, and 30.6 degrees 28 for copper Ka
radiation. These values are in good agreement
with the literature values of 28 = 31.4, 21.0 and
30.3 [ASTM Data (30)] and 28 = 31.8, 21.3, and
30.6 [JCPDS Data (3111.
374 HENRY C. STOBER

T y p i c a l i n s t r u m e n t a l and experimental c o n d i t i o n s
used t o o b t a i n t h e x-ray powder d i f f r a c t i o n
p a t t e r n of l i t h i u m carbonate d e p i c t e d i n F i g u r e 2
(32) a r e p r e s e n t e d below.

I n s t r u m e n t a l Conditions

Spectrometer: Diano 8535 D i f f r a c t o m e t e r

Generator: 30 KV, 13 mA
Tube T a r g e t : cu 0

Radiation: Cu, N i F i l t e r e d , Ka = 1.542 A

Optics : lo Beam S l i t , MR S o l l e r S l i t , 0.1'
D e t e c t o r S l i t , 3 O Take-Off Angle
Goniometer: Scan Rate: 2 degrees 29/minute
Detection: SPG-10 D e t e c t o r
Rate meter 2500 cps f u l l s c a l e
P u l s e Height S e l e c t i o n , EL = 0.2V

Sample
-
Sample was ground, s i e v e p t E r o u g h a
10
Preparation: No. 100 US Standard Sieve, and back-
packed i n t o an aluminum sample h o l d e r .

X-Ray Powder D i f f r a c t i o n P a t t e r n o f
Lithium Carbonate (USP)

MAJOR LINES

28 Degrees * dJ;J, 1/10 Hdc

21.4 4.15 84
23.5 3.79 18
29.5 3.03 24
30.6 2.92 81
31.6 2.83 100
34.1 2.62 31
36.1 2.49 19
36.9 2.43 40
39.7 2.27 19
48.8 1.87 15

f 28 degrees read t o n e a r e s t 0 . 1 degrees 28

nh
*k Interplaner Distance (1): d = 2 Sin 8
 Figure 2: X-Ray Powder Diffraction Pattern of Lithium Carbonate

.
h
u

I
m
2 .
u
C
H

$
-74
u
cd
4
d
b

s
ry

* .
7 U
1

15
I

19 23 27 31 35 39 43 47 Degrees 28
376 HENRY C . STOBER

+d** RelativeIntensity in percent based on strongest

signal. Under the experimental conditions employed
the relative intensities are subject to change due to
variations in sample handling and particle size and
are only included as a guide for identifying strong
lines.

The Hanawalt indices for lithium carbonate are 2.8lX,

4.168 and 2.928 (33).

2.13 Polymorphism
Recent literature indicates that up to its fusion
temperature lithium carbonate exists as only one
crystal form (18). An earlier report in the
literature indicated the presence of a
polymorphic transition at 166OC (17). The
possibility of lithium carbonate existing as a
stable c1 and a metastable f3 phase, under atmo-
spheric conditions, also has been proposed (34).
It should be noted, however, that in the
crystalographic sources consulted (30, 31, 33)
only one form of lithium carbonate is listed,
implying that other crystalline forms are
uncommon.

Impurities present in lithium carbonate may

account for some of the thermal effects noted.
In this respect, Reisman reported an anomalous
transition at -410OC and an additional heat
effect at 35OOC (18). The later was suspected to
be due to the presence of Li20. Impurities such
as Li20, Na2C03 and K2CO3 are known to form
eutectics with lithium carbonate and may account
for some of the anamolies observed. The ternary
eutectic with Na2C03 and K2CO3 melts at 397O (19)

2.14 Solubility
The following equilibrium solubility data was
obtained either experimentally at 37OC (6) or
from the literature as indicated in Table VI.
LITHIUM CARBONATE 377

TABLE VI

Solubility of Lithium Carbonate in Common Solvents

Solvent Solubility Source

(g/lOO ml)

Water, O°C 1.5 (25)

Water, 37OC 1.0 experimental
Water, 100°C 0.7 (25)
0.1N NaOH, 37OC 1.1 experimental
1.ON NaOH, 37OC 1.7 experimental
0.05M tris-buffer, 37OC 1.1 experimental
Ethanol Insoluble (25)
Acetone Insoluble (25)

Lithium carbonate decomposes in strong mineral

acids to yield carbonic acid, carbon dioxide and
the conjugate salt. The solubility of lithium
carbonate in water has been extensively studied
as a function of temperature and has been ob-
served to have a negative temperature coefficient
of solubility; the solubility decreasing signifi-
cantly with increasing temperature (35, 36). The
heat of solution of lithium carbonate in water at
25OC has been reported as -14,800 20.021 kJ mol-'
(37) *
When considering the solubility of lithium
carbonate in aqueous solutions, it should also be
noted that lithium forms insoluble salts with
several common anions including phosphate,
fluoride and the carboxylate anion of the C14
- C ~ Bfatty acids (25).

The solubility product of lithium carbonate in

water at 25OC is 1.7 x (38) when the concen-
tration of the lithium and carbonate ions are
expressed in moles/liter.

2.15 Dissolution
The intrinsic dissolution rate of lithium carbon-
ate in aqueous solutions was reported by Wall and
co-workers (39) using the rotating disc method.
They found linear dissolution rate profiles for
378 HENRY C. STOBER

lithium carbonate in water, simulated gastric

fluid and tris buffer. Dissolution studies in
simulated intestinal fluid containing phosphate
were complicated by the precipitation of trilith-
ium phosphate onto the disc.

Dissolution rate determinations for various

experimental and commercial lithium carbonate
preparations have been reported in the literature
(40 - 4 4 ) . Ritschel and Parab ( 4 3 ) evaluated
seven (six conventional and one sustained re-
lease) lithium carbonate commercial prepara-
tions. For the conventional preparations they
found a good correlation between the ENSLIN
number and t ( 5 min.), t (10 min.) and MRT (mean
residence time). The ENSLIN number (amount of
water in mL absorbed by 1 g of powdered sub-
stance) is a measure of the hydrophilicity, or
wetting, of the formulation.

The wetting of pharmaceutical powders, including

lithium carbonate, has also been evaluated by
Lerk and co-workers ( 4 5 ) using contact angle
measurements. The contact angle 8 obtained for
lithium carbonate by these workers was SO0 indi-
cating hydrophilicity.

3. Preparation of Lithium Carbonate

Lithium carbonate is primarily prepared from the

mineral spodumene, LiAlSizOs ( 4 6 ) . Other mineral
sources of lithium include petalite (LiAlSi4010),
amblygonite (LiAl[F,OH]PO4) and lepidolite
(K2Li3A14Si702[0H,F]3). Spodumene is the most commer-
cially important o f the lithium ores because of its
relative abundance and its relatively high lithium
content (3.757,).

In the manufacturing process employed by the Lithium

Corporation ( 4 7 ) spodumene crude ore, which also
contains such components as mica, quartz and feldspar,
is crushed to a fine sand. The crushed spodumene is
separated from the other components by flotation. The
“purified” spodumene is subjected to intense heat
(approximately llOO°C) and milled to a fine powder to
increase its surface area and reactivity. The powdery
LITHIUM CARBONATE 379

spodumene is treated with strong sulfuric acid at

25OoC to produce lithium sulfate (LiZSO4). The
lithium sulfate produced is separated from the residual
insoluble components of the ore by aqueous dissolution.
The resulting lithium sulfate solution is reacted with
sodium carbonate to produce lithium carbonate, which
remains in solution. Impurities yielding insoluble
carbonates are precipitated in this step. The lithium
carbonate solution is further purified by pH adjustment
and filtration and concentrated by evaporation. Lith-
ium carbonate is precipitated from the concentrated
solution by further treatment with sodium carbonate.
Pharmaceutical grade material is also further processed
to meet compendia1 and special requirements such as
particle size and bulk density. The flow chart depicted
in Scheme I summarizes the process just described.

Other processes reported to utilize spodumene involve

treatment with limestone to produce lithium hydroxide
( 4 6 ) and direct recovery of lithium carbonate by
digestion with aqueous sodium carbonate at 200°C ( 4 8 ) .
The production of lithium carbonate from lithium
hydroxide has been accomplished using carbonization
(COz) ( 4 9 ) and treatment with urea (50).

A procedure for purifying lithium carbonate by suspen-

sion in boiling water is described in Volume I of
"Inorganic Synthesis" ( 5 1 ) . The procedure is based on
the fact that lithium carbonate is less soluble in hot
water than in cold water, in contrast to the salts
that are present as impurities. A zone melting
procedure for producing single crystals of lithium
carbonate has also been described ( 5 2 ) .

4. Stability

4.1 Solution
The predominant stability problem for lithium
carbonate in aqueous solutions occurs in acid
solutions, in which it decomposes to yield the
lithium salt of the acid, bicarbonate, carbonic
acid and ultimately, carbon dioxide.

Solutions of lithium carbonate are also incompat-

ible with a variety of cations and anions.
380 HENRY C . STOBER

SCHEME I
Preparation of Lithium Carbonate from Spodumene

I Mined
Spodumene
Crushina I

'
Fine
Spodumene

I Ore Milling Ore

1
Powdery
Spodumene

1
-
I
Sintering
(1lOO"C)

Size
Reduction

(250OC)

Solution Solution

I
Lithium
Carbonate
Filtration
Evaporation
Sodium
Carbonate

Solid
LITHIUM CARBONATE 38 I

Cations such as calcium and barium, whose carbon-

ate salts are much less soluble than lithium
carbonate, and anions such as phosphate, that
form less soluble lithium salts, should be
excluded from lithium carbonate preparations.

4.2 Solid State

Light
-
Pharmaceutical grade lithium carbonate was
subjected for one week to visible light, whose
intensity was 600 foot candles (6). No decompo-
sition as noted by changes in physical appearance
(color, texture), weight and titrimetric assay
for carbonate was observed.

Therma1
Samples of lithium carbonate were stored in open
weighing dishes at 25OC and 105OC, respectively,
for one week (6). A small increase in the
titrimetric assay for carbonate from 99.4% to
99.6% was observed for the sample stored at
105OC. No change in the assay was noted for the
sample stored at 25OC. No measureable changes in
weight or physical appearance were observed for
either sample. This stable behavior for lithium
carbonate in the solid state is confirmed by the
literature (16, 17, 21). Accordingly, the lowest
temperature at which lithium carbonate has been
reported to begin to dissociate to lithium oxide
and carbon dioxide is 2OOOC (21). Other workers
have reported that dissociation occurs only near
the melting temperature (15, 16).

Humidity
Samples of lithium carbonate stored for one week
at 25OC/85% RH, 35OC/lO% RH and 35OC/85% RH were
essentially weight stable (6). This is consis-
tent with the literature (8, l o ) , which indicates
that lithium carbonate is not very hygroscopic.

5. Methods of Analysis

5.1 Identification Test for Lithium (2)

When lithium carbonate is moistened with hydro-
chloric acid, it imparts an intense crimson color
to a non-luminous flame.
382 HENRY C. STOBER

5.2 Identification Test for Carbonate (2)

Lithium carbonate effervesces upon the addition
of an acid, yielding a colorless gas, which when
passed into a solution of calcium hydroxide,
immediately causes a white precipitate to form.

5.3 Microchemical Test for Lithium

The microscopic identification of lithium is
practical oniy in materials in which lithium is
present in relatively high concentrations.
Identification has been achieved by preparation
of the tri-lithium phosphate salt, which forms
star-like clumps (53), the pyroantimonate salt,
which gives hexagons (53) and an orange-brown
aurate salt (54). In the absence o f other alkali
metals lithium reacts with zinc uranylacetate to
yield regularly developed octahedra (55).

5.4 Microchemical Test for Carbonate

Absorption of carbonate, evolved upon acidifica-
tion of a lithium carbonate preparation, by a
hanging drop of lead acetate, gives rise to
acicular crystals occurring singly or in irregu-
lar aggregates. Both bicarbonate and carbonate
give a positive response under these conditions.
When added directly, thallus acetate does not
precipitate with bicarbonate, but forms colorless,
long, slender needles with carbonate (56).

5.5 Volumetric Analysis

Lithium carbonate is analyzed in the USP ( 2 ) , BP
( 3 ) and ACS Reagent Chemicals (57) by titration
of the carbonate anion. Excess strong acid is
added to a solution of lithium carbonate and the
residual acid remaining after neutralization is
back-titrated with sodium hydroxide. Differences
exist between these methods with respect to the
indicators used and the emphasis placed on
expulsion of carbon dioxide after acidification.
Alternatively, potentiometric end point detection
can be accomplished using glass and calomel
electrodes.
LITHIUM CARBONATE 383

5.6 Atomic Emission and Absorption Spectroscopy

Solutions of lithium carbonate are frequently
analyzed for lithium using emission techniques
such as flame photometry, plasma spectroscopy and
by atomic absorption. The methods typically
employ analysis at a wavelength of 670.8 nm,
which is the most sensitive specific lithium line
(2, 1 4 ) . These techniques are particularly
effective for the analysis of lithium in dosage
forms and biological fluids (2, 40, 4 4 , 58). A
detailed discussion of the analysis of lithium in
biological fluids and tissues by flame photometry
and atomic absorption is presented in the text
"Lithium Research and Therapy" (59).

5.7 Other Spectrometric Techniques

Lithium carbonate has been determined
spectrophotometrically in tablets using the color
formed upon complexation of lithium with a
"crowned" dinitrophenylazophenol ether (60). The
purple color produced is stable and the absor-
bance of the solution measured at 560 nm is
linear over the concentration range from 25 to
250 ppb. Field desorption mass spectrometry
(FD-MS) in conjunction with a multichannel
analyzer has proven to be a useful tool for trace
analysis of lithium (61). The method also allows
for the determiation of the isotopic distribution
of the lithium salt analyzed.

5.8 Conductivity
Although nonspecific, conductimetric methods have
been used for the analysis of strong electrolytes
(62). The methods tend to be easily automated.
The technique is comparatively simple and appli-
cable to the dissolution rate determination of
dosage forms providing that the other conducting
components of the formulation are not present in
significant amounts. It has been used success-
fully in the authors laboratory for the determi-
nation of the dissolution rate of lithium
carbonate sustained release formulations in water
(63). Precautions were required against absorp-
tion of atmospheric Cop. This was accomplished
by performing the dissolution rate studies with
the vessels under a steady stream of nitrogen.
384 HENRY C. STOBER

5.9 Ion Selective Electrodes

Several workers have explored the usefulness of
ion selective electrodes for the analysis of
solutions of lithium (64, 65, 66). The elec-
trodes are limited by comparatively poor Li+/Na+
selectivity. This deficiency is especially
apparent in biological fluids where comparatively
high levels of Na+ are encountered. Using
elecrodes based on PVC membranes containing ETH
1810 as a neutral carrier, Metzger and co-workers
(64) obtained recoveries of lithium in serum to
within +_lo% over the clinically relevant concen-
tration range.

5.10 Ion Chromatography

Aqueous solutions of lithium carbonate can be
readily analyzed for lithium by ion
chromatography. A polystyrene-divinyl benzene
sulfuric acid cation exchanger in the hydrogen
form (Waters, IC-PAC-C) and 2 mM nitric acid
eluent is employed (67). Under these conditions
lithium at the ppm level is readily separated
from sodium and potassium at comparable concen-
trations. The carbonate anion can also be
determined using a polymethacrylate anion ex-
changer in the quaternary ammonium ion form
(Waters, IC-PAC-A).

6. Medicinal History (68, 69)

Lithium, the lightest of the alkali metals, was

discovered in 1817 by Arfwedson. Its salts were later
found in the spa waters of Germany and England, where
it was believed that it was therapeutic in the treat-
ment o f rheumatoid arthritis and gout. Its use-
fulness in the treatment of gout was attributed to the
high solubility of lithium urate. The use of lithium
as a uricosuric prompted J. F. Cade in Australia to
give animals a lithium salt to decrease the nephrotox-
icity of uric acid. He noted that the lithium salt
produced a calming effect in the animals and proceeded
to use lithium salts clinically as a sedative. During
the 1950's and 1960's the clinical use of lithium
LITHIUM CARBONATE 385

salts was intensely investigated in Europe, where it

became accepted as an effective and safe treatment for
manic depressive illness.

Lithium salts were not accepted in the United States

until 1970. This was due in part to concerns about
the safety of lithium salts after several deaths were
reported (1949-50) among patients using large amounts
of lithium chloride as a salt substitute. Although
several lithium salts such as the chloride and bromide
have been used, lithium carbonate is preferred because
of its relative stability (it is less hygroscopic than
the halogen salts) and it is less irritating to the
gastrointenstinal tract.

7. Pharmacology (69, 70)

Lithium carbonate is usually administered as 300 mg

tablets or capsules. Each 300 mg of the carbonate
contains 8.12 mEq of lithium. The usual daily dose of
lithium carbonate for prophylactic therapy is 600 mg
to 1200 mg.

Lithium is readily absorbed after oral administration

in the gastrointestinal tract, peaking in the plasma
within 1 to 3 hours and tends to distribute evenly
throughout the total body water space. Lithium is not
bound to plasma proteins. There is some lag in
penetration into the cerebrospinal fluid, but there is
no absolute barrier to its entry into the brain.
Equilibration of lithium between the blood and the
brain is almost complete within 24 hours.

The "metabolism" of the lithium ion is almost entirely

via the kidneys. About half of a single dose of lith-
ium is excreted in 24 hours. An important feature of
the renal excretion of lithium is that its rate is not
typically increased by the administration of most
diuretics. Increased administration of sodium appears
to have minimal effect on the normal excretion of
lithium, while depressed in-vivo levels of sodium fac-
ilitate lithium retention. These physiological fac-
tors have important implications for the management of
lithium intoxication. The therapeutic plasma range
(0.5 - 1.5 mEq/L) and the toxic plasma levels (>1.6
mEq/L) are very close and monitoring is performed at
386 HENRY C. STOBER

the onset of therapy. The mechanism of action of

lithium ion in manic depression is not clearly under-
stood. Lithium interferes with the action of the
catecholamines in the brain. This supports the
popular hypothesis that in mania catecholamines may be
functionally overactive in the brain. The role played
by lithium may also be related to competition with
sodium ions in body sites, such as electrolyte balance
across cell membranes, including those of the neurons.

Acknowledgement
The typing assistance o f Mrs. Frances Ghiazza in the
preparation of this manuscript is appreciated.
LITHIUM CARBONATE 387

References

1. Merck Index, 10th ed., Merck and Co., Rahway, NJ

(1983) page 5344.

2. The United States Pharmacopoeia XXI, Mack Publishing

Co., Easton, PA (1985) page 602.

3. British Pharmacopoeia 1980, University Press,

Cambridge, England (1980) page 259.

4. Modern Drug Encyclopedia and Therapeutic Index, G. D.

Gonzales, ed., York Medical Books, New York, NY 14,
(1977) page 492.

5. Remington's Pharmaceutical Sciences, 17th ed., Mack

Publishing Co., Easton, PA (1985) page 1088.

6. G. Dolch and H. Stober, CIBA-GEIGY Corp., Internal

Communication, ARD 77121.

7. K. Bruijs and C. J. H. Schutte, Spectrochem. Acta,

-
17, 927 (1961).

8. M. H. Brooker and J. B. Bates, J. Chem. Phys., 54,

4788 (1971).

9. F. A. Miller and C. H. Wilkins, Anal. Chem., -

2 4 , 1253
(1952).

10. D. E. Chasan and G. Norwitz, Appl. Spectrosc., 28,

195 (1974).

11. P. Tarte, Spectrochem. Acta, 3,238 (1963).

12. M. H. Brooker and J. B. Bates, J. Chem. Phys., 54,

(1971).

13. J. B. Bates, M. H. Brooker, A. S . Quist and G. E.

Boyd, J. Phys. Chem., 76, 1565 (1972).

14. Analytical Methods for Atomic Absorption Spectrometry,

Perkin Elmer Corp. Norwalk, Conn., 1976.
388 HENRY C.STOBER

15. M. Thompson and J. N. Walsh, A Handbook of Inductively

Coupled Plasma Spectrometry, Blackie (1983) London,
England, page 102.

16. T. V. Rode, Chem. Abstr., 48, 8697 (1954).

17. M. N. Sermenov and T. V. Zabolotskii, Chem. Abstr.,

-
48, 8697 (1954).

18. A . Reisman, J. Am. Chem. SOC., 80, 6853 (1962).

19. G. J. Janz, E. Neuenschwander and F. J. Kelly, Trans.
Faraday SOC., 59, 841 (1963).

20. I. S . Rassonskaya and N. K. Semendyaeva, Chem. Abstr. ,

59, 8158 (1963).
-

21. T. E. Machaladze, G. D. Chachanidze and R. N.

Pirtskhalava, Chem. Abstr., 2,1214112 (1973).

22. G. Papin, Chem. Abstr., 80, 53148n (1974).

23. Comprehensive Inorganic Chemistry, Vol. 1,

Pergamon Press Ltd., Oxford, Great Britain (1973)
page 335.

24. Data Sheet €or Lithium Carbonate Pharmaceutical,

Lithium Corporation of America, North Carolina, USA.

25. Handbook of Chemistry and Physics, 66th ed., The

Chemical Rubber Co., Cleveland, Ohio (1985) page
B108.

26. R. Morris, CIBA-GEIGY Corp., Personal Communication.

27. Handbook of Chemistry and Physics, 66th ed., The

Chemical Rubber Co., Cleveland, Ohio (1985) page
D163.

28. Crystal Data Determination Tables, 3rd. ed., Vol. 2.

Inorganic Compounds, JCPDS (1973).

29. J. Zemann, Acta. Cryst., lo, 664 (1957).

30. Index to Powder Diffraction, ASTM (1963).

31. Powder Diffraction Data, JCPDS, 1st ed. (1976) 349.

LITHIUM CARBONATE 389

32. L. Busch, CIBA-GEIGY Corp., Personal Communication.

33. Inorganic Phases Powder Diffraction File, JCPDS

(1982),

34. A . N. Khlapova and E. S. Koraleva, Chem. Abstr.,66,

230492 (1967).

35. S. H. Smith, Jr., D. D. Williams and R. R . Miller, J.

Chem. Eng. Data, 16,74 (1971).

36. V. M. Elenevskaya and M. I. Ravich, Chem. Abstr., 56,

8702q (1962).

37. R. L. Montgomery, R . A. Melaugh, C. C. Lau, G. H.

Meier, R. T. Grow and F. D. Rossini, Chem. Abstr. 89,
4969b, (1978).

38. Handbook of Chemistry and Physics, 66th ed., The

Chemical Rubber Co., Cleveland, Ohio (1985), page B222

39. B. P. Wall, J. E. Parkin and V. B. Sunderland,

J. Pharm. Pharmacol., 37, 338 (1985).
40. B. P. Wall, J. E. Parkin, V. B. Sunderland and A .
Zorbas, J. Pharm. Pharmacol., 34, 601 (1982).

41. R. E. Shepard, J. C. Price and L. A. Luzzi, J. Pharm

Sci. -361 1152 (1972).
-9

42. H. C. Caldwell, J. Pharm. Sci., -

63, 770 (1974).

43. W. A. Ritschel and D. Parab, Drug Dev. and Indus.

Pharm
-9 11
-9 147 (1988).

44. T. E. Needham, D. David and W. Brown, J. Pharm. Sci.,

-
68, 952 (1979).

45. C. F. Lerk, M. Lagas, J. P. Boelstra and P.

Broersama, J. Pharm. Sci., 66, 1481 (1977).

46. W. A . Hart and 0. F. Beumel, Jr. Comprehensive Inor-

ganic Chemistry, Vol. 2 , Chapt. 7, A. F. Trotman-
Dickensen ex. ed., Pergamon Press, Elmsford, NY (1973).

47. Lithium, Lithium Corporation of America, Gastonia,

North Carolina (1985).
390 HENRY C . STOBER

48. C. A. Oliver, E. H. Nenniger, Chem. Abstr., 91,

12451h (1979).

49. E. B. Gitis, F. I. Strigunov, I. D. Solyanik, G. A.

Trutnev, Chem. Abstr., 97, 130000P (1982).

50. Chem. Abstr., 101,93728k (1984).

51. F. R. Coley and P. J. Elving, Inorganic Synthesis,

Vol. 1, Chapter 1, H. S. Booth, ed., McGraw-Hill,
New York, NY (1939).

52. P. Ramasamy, G. S . Laddha, Cryst. Res. Technol., l7,

911 (1982).

53. E. M. Chamot and C. W. Mason, Handbook of Chemical

Microscopy, Vol. 2 , John Wiley, New York, NY (1931))
87.

54. C. F. Fulton, Modern Microcrystal Tests for Drugs,

John Wiley, New York, Ny (1969)) 73.

55. A. A. Benedetti-Pichler, Identification of Materials

via Physical Properties, Chemical Tests and Microscopy,
Springer Verlog, New York, NY (1965)) 325.

56. E. M. Chamot and C. W. Mason, Handbook o f Chemical

Microscopy, Vol. 2, John Wiley, New York, NY (1931) ,
296.

57. Reagent Chemicals, 6th ed., American Chemical

Society, Washington, D.C. (1982), 321.

58. A . Palladino, Jr., R. G. Longenecker, L. J. Lesko,

J. Clin. Psychiatry, 5, 7 (1983).
59. Lithium Research and Therapy, F. N. Johnson, ed.,
Chapters 10 and 11 , Academic Press, New York, NY
(1975).

60. K. Nakashima, S. Nakatsuji, S. Akiyama, T. Kaneda, S .

Misumi, Chem. Letters, 11, 1781 (1982).

61. W. D. Lehman, H. R. Schulter, Angew. Chem. Int. Ed.

Engl. , 16,852 (1977).
LITHIUM CARBONATE 39 1

62. H. H. Willard, L. L. Merrit, J. A. Dean, Instrumental

Methods of Analysis, 4th ed., Chapter 2, D. Van
Nostrand Co. Inc., New York, NY (1965).

63. G. Dolch and H. Stober, CIBA-GEIGY Corp., Internal

Communication, ARD 77135.

64. E. Metzer, D. Ammann, R. Asper and W. Simon, Anal.

Chem. -958 132 (1986).
-9

65. S. Kitazawa, K. Kimura, H. Yano and T. Shono,

Analyst, 110, 295 (1985).

66. A. F . Zhujow, D. Erne, D. Ammann, M. Guggli, E.

Pretsch and W. Simon, Anal. Chem. Acta., 131, 117
(1985).

67. Waters L. S. Series Ion/Liquid Chromatographs,

Operators Manual, Chapter 3, Millipore Corp., Waters
Chromatography Div., Milford, MA (1985).

68. Lithium Research and Therapy, F . N. Johnson, ed.,

Chapters 1 and 2. Academic Press, New York, NY
(1975).

69. Handbook o f Psychopharmacology, L. L. Iversen, S. D.

Iversen and S. H. Snyder, ed., Chapter 6 , Plenem
Press, New York, NY (1978).

70. Lithium Research and Therapy, F . N. Johnson, ed.,

Chapters 16, 17, and 18, Academic Press, New York,
NY (1975).