Evaluation of a New Antacid, Almagate

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From Research Institute, Laboratorios Almirall, Barcelona (Spain)
Evaluation of a New Antacid, Almagate
By J. E. Beneyto, J. L. Fábregas, J. Moragues, and R. G. W. Spickett
Summary: Almagate (AI2Mg6(OH)14(C0 3)2· 4 H 20, Alma:x.®), a crystal/ine hydrated aluminium-magnesium hydroxycarbonate, was compared with a number of other
known antacids in a battery of tests designed to demonstrate
the properties of an ideal antacid. In dynamic tests for measurement of velocity of neutralization, total acid consuming
capacity and duration of activity, almagate like other crysta/line aluminium magnesium hydroxide derivatives such as
hydrota/cite and magaldrate was rapidly acting, neutralized
a high proportion of its theoretical acid consumption and
maintained gastric pH between 3 and 5 for a prolonged period of time. It was more active than these two substances in
respect of rapidity of action and did not lose antacid activity
as the pH was raised. Like these compounds it had considerable advantages over the amorphous gels and co-gels of aluminium and magnesium hydroxides or hydroxycarbonates
in respect of both rapidity of action and acid consuming capacity. It inhibited the activity of pepsin and was shown to
adsorb bile acids and had a low sodium contento
Zusammenfassung: Bewertung eines neuen Antazidums, Almagat
Almagat (AI2Mg6(OH)llC03)2· 4 H 20, Alma:x.®), ein kristal/ines Magnesiumaluminiumhydroxydcarbonat-tetrahydrat,
wurde mil einer Reihe anderer bekannter Antazida verg/ichen mittels einer Testreihe zur Demonstration der Eigenschafien eines idealen Antazidums. In dynamischen Tests
zur Messung der Neutralisationsgeschwindigkeit, der gesamten Siiurebindungskapazitiit und der Wirkungsdauer
zeigte Almagat wie andere kristal/ine AluminiumMagnesium-Hydroxyd-Derivate - beispielsweise Hydrotalcit
und Magaldrat - schnelle Wirkung, neutra/isierte einen hohen Anteil seines theoretischen Siiureverbrauchs und hielt
den pH- Wert im Magen über einen liingeren Zeitraum hin-
weg bei 3 bis 5. Es übertraf diese beiden Substanzen in der
Schnelligkeit der Wirkung und verlor nicht an siiurebindender Aktivitiit, wenn der pH- Wert erhOht wurde. Wie diese
Substanzen zeigte Almagat betriichtliche Vorteile gegenüber
den amorphen Gelen und Cogelen aus Aluminium- und
Magnesiumhydroxyden oder Hydroxycarbonaten hinsichtlich sowohl der Schnelligkeit der Wirkung als auch der
Siiurebindungskapazitiit. Es hemmt die Aktivitiit von Pepsin, adsorbiert Harnsiiuren und hat einen niedrigen
N atrium-Gehalt.
Resumen: Evaluación de un nuevo antiácido: almagate
Se ha comparado almagate (AI2Mg6(OH)14(C0 3)2· 4 H 20,
Alma:x®) nuevo hidroxicarbonato hidratado cristalino de
aluminio y magnesio, con algunos otros antiácidos conocidos, en una serie de ensayos destinados a demostrar las propiedades de un antiácido ideal. En los ensayos dinámicos
para medir la velocidad de neutralización, la capacidad de
consumo de ácido total y la duración de su actividad, almagate, al igual que otros derivados de hidróxidos cristalinos de
aluminio y magnesio, como la hidrotalcita y el magaldrate,
actuó rapidamente, neutralizando una elevada proporción
de su consumo ácido teórico, manteniendo el pH gástrico
entre 3 y 5 durante mucho tiempo. Almagate ha resultado
más activo que aquellos dos productos con respecto a la rapidez de acción, no perdiendo su actividad antiácida al elevarse el pH. Al igual que los mencionados antiácidos tiene
considerables ventajas sobre los geles amorfos y los co-geles
de los hidróxidos de aluminio y magnesio o los hidroxicarbonatos tanto por lo que se rejiere a su rapidez de acción
como a su capacidad de neutralización. Almagate ha inhibido la actividad de la pepsina y ha demostrado su capacidad de absorción de ácidos biliares y su bajo contenido en
sodio.
Key words: Almagate, in vitro studies· Alma:x®· Aluminium-magnesium hydroxycarbonate· Antacids· Bile acids,
inhibition . Pepsin, inhibition
l. Introduction
In spite of the development of new systemically acting drugs,
particularly histamine H 2 -blocking agents, antacids continue
to be widely used in the treatment of gastrointestinal disorders related to excretion of excess gastric acid [1], e.g. gastric
and duodenal ulcers, gastritis, etc. However, due to the different factors affecting the pathogenesis of these disturbances
[1-7] measurement of acid neutralizing capacity only is insufficient to evaluate the therapeutic efficacy of an antacid.
It is generally agreed that an ideal antacid should possess a
high acid neutralizing capacity and a rapid velocity of neutralization, in order to cope with the rate of stomach, emptying [8]. The gastric contents should not be ovemeutralized
to avoid a rebound effect, the optimum pH should be in the
1350
range from 3 to 5 [7-11], the buffering potency in this range
of pH should be high in order to attain a long-Iasting antacid
effect. The antacid activity should also be unaffected by
digestive enzymes, particularly pepsin. Even though a reduction of the hydrogen ion concentration inhibits to sorne extent the activity of pepsin, it still retains 70% of its activity
at 4.5 [11]. Since it appears [12] that the final event in the
pathogenesis of ulcers may be the proteolytic digestion of
gastric mucosal cells, an antacid should inhibit the activity
of pepsin in the pH range of 3 to 5 [11, 13]. Additionally, an
antacid should adsorb bile acids without changing enterohepatic circulation, since it has been shown [14] that gastrointestinal reflux of bile acids is implicated in the pathogenesis of digestive disorders. Most commercially available
A.rzneim.-Forsch.l Drug Res. 34(11), Nr. lOa (984)
Beneyto et al. - A.lmagate
antacids contain sodium [15] and the intake of sodium may
exceed minimal adult requirements. A high content of sodium may be distinctly dangerous for patients with associated sodium-retaining diseases, consequently an antacid
should have the lowest sodium content possible.
In this publication the behaviour of almagate (AhM&;
(OH)14 (C0 3)2 • 4 H 20, Almax®I», a new crystalline aluminium-magnesium hydroxycarbonate [16], is compared with
other products commonly employed as antacids in a range
of tests designed to demonstrate its utility as an antacid.
water and the determination of bile acid at zero time carried out by
Pettenkofer's procedure [24]. To the remaining solution, antacid
powder seived to 100 mesh (500 mg) was added with vigorous stirring and the pH was kept constant during the experiment by addition of I mol/I HCI with a radiometer automatic potentiometric
titrator at pH-stat 7. At intervals from I up to 3 h, samples (2.0 mi)
of the suspension were removed, observing the volume of I mol/I
HCI that had been added, and centrifuged at 3000 rpm. The supernatant (1 mi) was diluted to 5.0 mi with water as a zero time, and
the colorimetric determination ofbile acid carried out on these sampies.
The experiments were repeated using McIlvain buffer pH 4.
2. Materials
Almagate was synthesized in the Chemical Research Department,
Research Institute, Laboratorios Almirall, Barcelona (Spain). Dried
aluminium hydroxide gel, A-211, magaldrate, C-41O, aluminium
hydroxide-magnesium carbonate co-dried gel, C-220, magnesium
hydroxy carbonate and magnesium hydroxide were supplied by the
manufacturero Aluminium trisilicate, ca1cium silicate and all other
products were of analytical or phannacopoeial grade.
3.7. Sodium content
The sodium content of the antacids was determined with a PerkinElmer atomic absorption spectrometer model 2380.
3. Methods
3.1. Total acid consumption capacity
The official USP method [17] was adopted.
3.2. Neutralization curves (pH-stat method)
The methods used have been described previously [16].
4. Results
4.1. Total acid consuming capacity
The results obtained with the different antacids in the standard USP test are given in Table 1. The values obtained are
related to the molecular weights of the antacids. The highest
values being obtained with compounds which have the lowest molecular weight such as magnesium and aluminium
hydroxide. Almagate had an intermediate value within the
group of substances tested.
3.3. pH-profile and buffering capacity
An adaptation of the method of Holbert et al. [18], and Johnson et
al. [19], modified by Beckman [20] was used. The conditions were
similar to those described by Beckman but USP simulated gastric
juice containing pepsin was used [21].
Antacid powder (150 mg) previously sieved to 100 mesh, was
weighed, dispersed in USP artificial gastric juice (20 mi) at 37 ±
0.5 'C by mechanical stirring at constant velocity (900 rpm) and
maintained at this temperature throughout the experiment. The pH
was recorded during the first 10 min. The addition of fresh gastric
juice was then commenced at a flow rate ofO.7 mi min- I from the
auto-burette of a Radiometer automatic potentiometric titrator, and
the pH was measured until it fell below 3. The volume offresh gastric juice added up to this moment was observed.
3.4. Holbert's test [18]
The product (1 g) was added to USP artificial gastric juice (150 mi)
containing pepsin (2 g) whilst stirring rapidly and recording the pH
during the first 10 mino Fresh gastric juice was then added at a
velocity of 1.8 mi min- I using a peristaltic pump with two tubes,
one of which was used to add the gastric juice at exactly the same
velocity. The pH ofthe mixture was measured until the pH descended to 3.
3.5. Anti-pepsin activity
200 mg of antacid powder, previously sieved to 100 mesh, was suspended in 20 mi of USP artificial gastric juice at 37 ± 0.5 OC, stirred
at constant speed for 10 min and the first sample (1.0 mi) taken.
Fresh gastric juice was added at arate of 0.35 mi min- I , and samples
(1.0 mi) taken periodically and fresh gastric juice (1.0 mI) added
each time.
The samples were centrifuged separately and the pepsin activity detennined by the modified Anson method [22]. The centrifuged sampie (5 Ill) was transferred to a 20 mi centrifuge tube containing substrate2) (5 mI) and incubated at 25 ± 0.1 'C for 10 min, when a 5%
w/v. aqueous solution oftrichloroacetic acid (10 mI) was added. The
resultant mixture was centrifuged at 2800 rpm for 10 mino To the
supematant (5 mi) was added 0.5 N NaOH (10 mi) and Folinciocalteu reagent (3 mi). After standing for 10 min the absorption at
578 nm was measured using water as reference. At the same time a
blank detennination was carried out by the same procedure using
only substrate solution (5 mi).
3.6. Bile acid adsorption
McIlvain buffer solution pH 7 (25 mi) [23] was introduced into a
flask at 37 ± 5 'C and bile acid solution (1 mi) was added. After
thorough agitation 1.0 mi was withdrawn and diluted to 5.0 mi with
1)
2)
Manufacturer: Laboratorios Almirall, Barcelona (Spain).
Substrate: A solution of haemoglobin (2 g) dissolved in 0.06 N
HCI (100 mi).
Arzneim.-Forsch.l Drug Res. 34 (11), N,. lOa (1984)
Beneyto el al. - Almagate
Table 1: USP acid neutralization capacity of several antacids.
Antacid
USP acid consuming capacity
(mEq Hel 151)
Almagate
Dried aluminium hydroxide gel
Magaldrate
Aluminium hydroxide-magnesium
carbonate dried co-gel
Magnesium hydroxycarbonate
Magnesium hydroxide
Aluminium-magnesium trisilicate
ealcium silicate
Hydrotalcite
28.3
32.0
24.0
27.9
21.9
32.6
19.0
9.8
30.7
4.2. Neutralization curves, pH-stat method
This dynamic test was developed by Kerhof et al. [25] to
overcome the criticisms of the static USP test. The amount
of gastric acid juice consumed in the pH stat test at different
pH values for the various antacid substances is shown in Table 2. The highest acid consumption is observed with substances which contain both aluminium and magnesium ions,
e.g., almagate, magaldrate, co-dried aluminium hydroxidemagnesium carbonate gel and hydrotalcite. All substances
have relatively high acid neutralizing effects at pH 2 but as
the pH is increased to 4, magnesium hydroxide and almagate retain the highest proportion of activity. Sorne of the
substances tested, e.g. aluminium hydroxide gel, magaldrate,
aluminium-magnesium trisilicate and hydrotalcite lose a
considerable part of their acid neutralizing capacity at pH 4.
Table 2: pH-stat acid consumption for several antacids.
Antacid
Almagate
Magaldrate
Magnesium hydroxide
ealcium silicate
Hydrotalcite
Acid consuming capacity
(mEq Hel 151)
pH2
pH3
pH4
39.0
26.6
36.5
27.7
10.5
25.0
17.3
4.4
9.3
39.9
18.6
32.6
26.4
13.3
35.7
27.4
16.4
22.7
16.2
6.9
27.4
13.1
16.2
21.8
5.6
6.1
8.8
1351
When the kinetic parameters, i.e. time required to neutralize
90% or 50% ofthe total acid consumed (Table 3), three general types of behaviour are observed. One group of compounds, magnesium hydroxycarbonate, calcium silicate and
aluminium hydroxide gel have similar reaction times for
90% neutralization at the three different pH values, the
former two having a rapid neutralizing effect and the latter
has a slow reaction velocity. A second group, ineluding malgadrate, magnesium hydroxide, aluminium-magnesium trisilicate, hydrotalcite and a co-gel of aluminium hydroxidemagnesium carbonate have an increased reaction time for
90% neutralization as the pH is increased. In the final group,
almagate has a similar reaction time for 90% neutralization
at pH 2 and pH 3 and this time increases when the reaction
is carried out at pH 4. The time required to neutralize
50% of the total acid consumed is variable at the different
pH values but only four substances, magnesium hydroxy
carbonate, calcium silicate, magnesium hydroxide and almagate neutralize 50% of their theoretical acid consumption in
less than 5.5 min at pH-stat 4.
4.3. pH-profile test
The results obtained in the pH profile test (Table 4) show
that magnesium hydroxy carbonate and magnesium hydroxide are excessively basic, raising the pH aboye 5.0 with a low
Rossett-Rice time and would consequently be expected to
cause a rebound effect in vivo. The silicates on the other
hand are not capable of increasing the pH aboye 3 and their
antacid properties are dubious [11]. Dry aluminium hydroxide gel and the co-gel of aluminium hydroxide-magnesium
carbonate have a low buffering effect probably related to the
slow velocity of reaction of aluminium hydroxide gels. The
group with rapid onset of action, high buffering activity,
high Rossett-Rice times, and with no acid rebound effect inelude, almagate, magaldrate, and hydrota1cite. These useful
properties may be related to their crystalline structure [16,
26] as opposed to the amorphous structure of the second
group [5, 27].
4.4. Holbert's test
The results obtained in this experiment (Table 5) demonstrate that almagate rapidly increases the pH aboye 3 and
maintains it in the desired zone of pH 3-5 for a prolonged
period oftime.
4.5. Antipepsin activity
Almagate and dry aluminium hydroxide gel were compared
in this test. The antipepsin activity of aluminium hydroxide
has been extensively studied [8, 11] and it has also been
shown to adsorb this enzyme [28, 29, 30]. The proteolytic
activity of pepsin is decreased as the pH of the reaction medium rises [5, 8, 11]. However, the variation of proteolytic
activity shown in Fig. 1 represent reallosses of activity since
the activity was measured in strongli acid solution [22]. In
the first ten minutes the proteolytic activity decreases to less
Table s: Time/pH profile ofalmagate in Holbert's test.
pH ofmixture
. Time (min)
o
1.27
3.92
4.27
4.50
4.50
4.45
4.38
4.17
4.02
3.86
3.66
3.42
3.14
2.89
2.70
1
2
4
6
8
10
20
30
40
50
60
70
80
90
Table 3: Kinetic parameters for different antacids in the pH-stat test.
pH-stat 2
pH-stat 3
pH-stat 4
Antacid
t90 min
tso min
Igo min
tso min
Igo min
tso min
Magnesium hydroxy-carbonate
Calcium silicate
Aluminium hydroxide gel
3.9
2.9
62.0
2.2
2.9
43.0
3.4
2.0
62.5
2.0
2.0
33.5
3.4
2.5
58.0
2.0
2.5
20.7
Magaldrate
Magnesium hydroxide
Hydrotalcite
7.3
6.5
5.5
13.2
4.2
3.6
2.5
3.8
16.5
11.8
16.8
20.5
3.0
2.6
5.2
6.2
46.0
34.0
46.0
55.0
7.8
4.5
8.5
17.1
14.7
4.6
37.7
9.6
43.5
7.2
7.5
4.3
6.8
3.4
37.0
5.4
Almagate
t90; neutralizatlOn tIme for 90% of total acid comsumption.
tso; neutralization time for 50% of total acid comsumption.
Table 4: pH-profile and buffering capacity parameters of several antaclds.
pH-profile
Antacid
Almagate
Magaldrate
Magnesium h ydroxycarbonate
Magnesium hydroxide
Calcium silicate
Hydrotalcite
a)
Acid rebound a)
time (min)
Max. pH
Buffering capacity
Acid consumption
(mEq HCI g_l)
34.6
14.8
31.5
0.0
0.0
0.0
4.24
3.56
3.80
25.8
17.5
22.6
16.7
4.6
15.4
0.8
0.0
35.8
0.0
24.8
13.5
0.0
0.0
0.0
3.73
7.36
6.85
3.05
>3.0
3.86
18.2
21.4
21.3
12.9
0.0
26.8
Lag timea)
(min)
Rossett-Rice time a)
(min)
0.1
4.8
0.1
1.7
0.1
0.3
9.6
>10
0.2
Rossett and RICe [32]
1352
Arzneim.-Forsch.! Orug Res. 34 (U), Nr. \ Oa (\984)
Beneyto et al. - Almagate
Table 7: Sodium content of several antacids.
Initial proteolytic activity ji,
Na content (ppm)
Antacid
100
<25
1200
360
Almagate
Magaldrate
Magnesium hydroxide
Calcium silicate
H ydrotalcite
80
60
40
39400
860
1 lOO
12400
1400
<25
Table 8: Acid consumption, pH-stat 3, and buffering capacity as a percentage
ofUSP total acid consumption for several antacids.
Antacid
pH-stat 3 (%)
Buffering
capacity (%)
97.7
32.8
104.0
95.9
54.7
94.2
98.2
74.8
69.5
65.2
97.7
65.3
85.1
70.7
84.0
67.9
0.0
89.1
20
time (min)
Fig. 1: Antipepsin activity of almagate (O---D) and of aluminium hydroxide gel (0---0).
than 5% of its initial value indicating that the inhibition is
due to adsorption phenomena [5, 8, 11] or to a pH reversible
precipitation ofpepsin by trivalent aluminium ions.
Inhibition of proteolytic activity was observed with almagate
during the dissolution time but after complete dissolution,
approx. 80 min (Fig. 1), the pepsin had recovered about 90%
of its original activity whereas with aluminium hydroxide
gel pepsin reactivation was slow.
4.6. Adsorption oC bile acids
The extent adsorption of bile acids by almagate is shown in
Table 6 where the amount of bile acids remaining in solution after 1 h and 3 h of reaction at pH 4 and 7 was measured.
Cholic and taurocholic acids and the acids present in ox bile
extract were adsorbed by almagate at pH 3 but at pH 7 none
of the substances were extensively adsorbed by almagate.
Table 6: In vitro adsorption ofbile acids by almagate.
% Bile acids remaining in solution
pH4
Bile acid component
Freeze-dried ox bile extract
Cholic acid
Taurocholic acid
pH7
1st hour
3rd hour
31.0
19.5
34.6
30.0
13.5
28.3
,1
1st hour
3rd hour
100.0
99.4
82.7
88.0
79.2
76.2
4.7. Sodium content
The sodium content of the different antacids is recorded in
Table 7. Variable sodium contents were found and almagate
was shown to contain low levels of sodium as would be expected from its method of preparation.
5. Discussion
Static in vitro tests for the determination of the utility of antacids under in vivo conditions have now been replaced by a
variety of dynamic in vitro tests designed to more closely
corre late with conditions likely to be encountered in everyday use of such compounds in clinical practice. Fordtran et
al. [31] have shown that acid neutralizing capacity at pH 3 is
related to the clinical effectiveness of an antacid product
whereas Beckman [20] and Steinberg et al. [10] have used
Arzneim.-Forsch.l Drug Res. 34 (11), Nr. lOa (1984)
Beneylo el al. - Almagale
Almagate
Dried aluminium hyd¡oxide gel
Magaldrate
Magnesium hydroxide
Aluminium-magnesium
trisilicate
Calcium silicate
Hydrotalcite
the pH profile test (buffering capacity) to reproduce in vivo
conditions. The results obtained in these two tests expressed
as a percentage of USP total acid consumption are shown in
Table 8. Only almagate and magaldrate consume practically
the theoretical amount of acid in these dynamic tests
whereas in the case of aluminium hydroxide gel only about
one third to one half of the theoretical amount is adsorbed.
The results obtained in a battery of tests evolved to dcmonstrate the properties of an ideal antacid have shown that almagate has the foIlowing properties. It has a rigid crystallattice which ensures optimal contact with gastric acid and
long-term stability. It rapidly neutralizes excess acid and has
a high acid adsorbing capacity maintaining the gastric pH
between 3 and 5 for a long period of time. It does not induce
overalkalinization or acid rebound effects and its antacid
activity is not influenced by the presence of polypeptides or
enzymes and it adsorbs and inactivates pepsin in the pH
range 4-5. At pH 4 almagate adsorbs and inactivates bile
acids implicated in a variety of disorders associated with gastro-duodenal reflux, but at the higher pH values encountered
in the duodenum where these substances have their physiological effect they are not adsorbed. Almagate has a low intrinsic sodium content.
The overall profile of almagate indicates that it compares favourably with other crystalline aluminium hydroxy carbonates or sulphates and in a number oftests is superior to these
products. Pharmacological and clinical studies carried out
with almagate have confirmed its utility as an effective antacid.
6. ReCerences
[1] Marks, J. N., Drugs 20, 283 (1980) - [2] Le Veen, H. H., Gastroenterology 8, 648 (1947) - [3] James, A. H., Pickering, G. W.,
Clin. Sci. 8, 181 (1949) - [4] Brody, M., Bachrach, W. H., Am. J.
Dig. Dis. 4, 435 (1959) - [5] Hollander, F., Ann. N. Y., Acad. Sci.
99,4 (1962) - [6] Fordtran, J. S., CoIlins, J. A., New Engl. J. Med.
274, 921 (1966) - [7] Malagelada, J. R., Carlson, G. L., Scand. J.
Gastroenterol. 14,67 (1979) - [8] Piper, D. W., Fenton, B. H., Gut
5, 585 (1964) - [9] Desai, S., Gibaldi, M., Kaning, J. K., J. Pharm.
Sci. 52, 871 (1963) - [10] Steinberg, W. H., Hutchins, H. H., Pick,
P. G., Lazar, J. S., J. Pharm. Sci. 54, 625 (1965) - [11] Person, K. O.
V., Burke, B., Acta Pharmacol. Toxicol. 19,219 (1962) - [12] Bergman, J., Person, K. O. V., Westling, H., Acta Med. Scand. 172, 637
(1962) - [13] Valerio, R., Buttoni, R., 11 Farmaco, Ed. pro 28, 276
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- [I6] Moragues, J., Beneyto, J. E., Fábregas, J. L., Spickett, R. G.
W., Arzneim.-Forsch./Drug Res. 34 (11), 1346 (1984) - [17] United
States Pharmacopoeia XX Ed., p. 993 (1980) - [18] Holbert, J. M.,
Noble, N., Grote, 1. W., J. Am. Pharm. Assoc. 37, 292 (1948) - [19]
Johnson, E. H., Duncan, J., Quart. J. Pharm. Pharmacol. 18, 251
(1945) - (20] Beckman, S. M., J. Am. Pharm. Assoc. 49, 191 (1960)
- [21] United States Pharmacopoeia XX Ed., p. 1105 (1980) - [22]
Anson, M. L., J. Gen. Physiol. 22, 79 (1939) - [23] Meites, L.,
Handbook of Analytical Chemistry, 5, 112, McGraw-Hill, New
York (1963) - [24] von Pettenkofer, M., Ann. Chem. Pharm. 52, 90
(1944) - [25] Kerkhoff, N. J., Vanderlann, R. K., White, J. L., Hem,
S. L., J. Pharm. Sci. 66, 1528 (1977) - [26] Serna, C. J., White, J. L.,
Hem, S. L., J. Pharm. Sci. 67, 324 (1978) - [27] Nail, W. L., White,
J. L., Hem, S. L., J. Pharm. Sci. 65, 1188 (1976) - [28] Komarov, S.
A., Komarov, O., Am. J. Digest. Dis. 7, 166 (1940) - [29] Se-
chifrin, H. J., Komarov, S. A., Am. J. Digest. Dis. 8, 215 (1941)[30] Piper, D. W., Fenton, B. H., Am. J. Digest. Dis. 6, 134 (1961)[31] Fordtran, J. S., Morawski S. G., Richardson, C. T., New Engl.
J. Med. 288, 923 (1973) - [32] Rossett, N. E., Rice, H. L., Gastroenterology 26, 490 (1954)
Acknowledgement
The authors are indebted to Pror. R. Cadorniga, Faculty of Pharmacy, Madrid University, for helpful discussions.
For the authors: Dr. R. G. W. Spickett, Instituto de Investigación,
Laboratorios Almirall, Calle Cardoner, 68-74, Barcelona, 08024
(Spain)
From Research Institute, Laboratorios Almirall, Barcelona (Spain)
Stability of Almagate and Pharmaceutical Formulations
Prepared from It
By J. L. Fábregas and J. E. Beneyto
Die unter beschleunigten Bedingungen gemessene Stabilitiit
von Almagat (Magnesiumaluminiumhydroxycarbonat-tetratalline synthetic hydrated aluminium-magnesium hydroxy- hydrat, AI2Mg6(OH)llCO J)2 • 4 H 20, AlmaxP'), einem neuen
carbonate antacid, and pharmaceutical formulations pre- synthetischen Antazidum, und seinen pharmazeutischen Zupared from it, were compared with other pharmaceutical for- bereitungen wurde mit derjenigen von anderen pharmazeumulations prepared from aluminium hydroxide gel or co- tischen Formulierungen aus Aluminiumhydroxyd-Gel oder
gels of aluminium-magnesium hydroxide. The antacid pro- Cogelen aus Aluminiummagnesiumhydroxyd verglichen.
perties of almagate, Almax tablets and suspension, did not Die siiurebindenden Eigenschafien von Almagat, Almaxchange during eight months storage at 60'C whereas pre- Tabletten und -Suspension veriinderten sich wiihrend einer
parations of aluminium hydroxide gel and aluminium- 8monatigen Lagerung bei 60 'C nicht, wiihrend Aluminiummagnesium hydroxide co-gel suffired considerable losses in hydroxyd-Gel und Aluminiummagnesiumhydroxyd-Cogel
acid neutra/ization capacity. Neither the X-ray diffraction betriichtliche Verluste in ihrer siiureneutralisierenden Kapanor the IR absorption spectrum of almagate changed during zitiit erlitten. Weder die Rontgendiffraktion noch das IRstorage for 8 months at 60·C. Thus almagate and pharma- Absorptionsspektrum von Almagat wies wiihrend der
ceutical formulations prepared from it are therma/ly stable 8monatigen Lagerung bie 60'C Veriinderungen auf Somit
and will maintain their antacid properties for long periods of sind Almagat und seine pharmazeutischen Zubereitungen
time unlike products prepared from aluminium hydroxide wiirmestabil und bewahren ihre siiurebindenden Eigenschafgels or aluminium-magnesium hydroxide co-gels.
ten über lange Zeitriiume im Gegensatz zu Formulierungén
aus Aluminiumhydroxyd-Gelen oder AluminiummagneZusammenfassung: Stabilitiit von Almagat und seinen phar- siumhydroxyd-Cogelen.
mazeutischen Zubereitungen
Summary: The stabi/ity under accelerated conditions of almagate (AI2Mg6(OH)llCO J)2' 4 H 2 0, AlmaXl") a new crys-
1354
Arzneim.·FOltCh.l Drug Res. 34 (!J). Nr. lOa (1984)
Fábregtls el al. - Almagate

Evaluation of a New Antacid, Almagate

Transcripción

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