ABSTRACT
Ferrous sulphate tablet is an oral salt
of iron. It is the cheapest form of medicinal iron supplement and it is
used in the treatment of iron deficiency anaemia. Iron deficiency is one
of the world’s most common nutritional deficiency diseases, affecting
infants, children and especially pregnant women as well as lactating
mothers. Various brands of ferrous sulphate tablets were assayed to
confirm the amount of iron content as claimed by the manufacturers, so
as to ensure maximum therapeutic effects during clinical use. Seven
different brands of ferrous sulphate tablets by different manufacturers
which were obtained from various pharmacy outlets in Delta State and
Anambra of Nigeria were assayed using the titrimetric method of analysis
as described by the British Pharmacopoeia (BP) 2012. They were also
tested for uniformity of weight by the method stated in the BP. All the
samples were found to contain iron content in an amount within the
percentage content of 95.0% - 105.0%. Also, no variation was found in
the weight of the samples. Therefore, these brands when administered can
bring about maximum therapeutic benefits during clinical use.
CHAPTER ONE
1.0 INTRODUCTION AND LITERATURE REVIEW
1.1 BACKGROUND
Assay methods in
pharmaceutical chemistry are essential to control the quality of
pharmaceutical product, as well as the quantity of the active
pharmaceutical ingredients in a formulated product. To do this, a whole
arsenal of chemical, physicochemical, biological, biopharmaceutical and
automated analytical techniques is employed for determining the
identity, purity, content, stability, safety and efficacy of drugs and
their formulations. [1]
Different forms of iron
are usually prescribed by physicians for patients and they rely on the
amount of iron claimed on the label. Determination of the precise amount
of iron (II) contained in ferrous sulphate tablet is therefore
important. Ferrous sulphate tablet has been assayed using various
analytical methods.
1.2 HISTORY OF IRON
Iron has for long been considered important for the body. Lauha bhasma (calcined
iron) has been used in ancient Indian medicine. According to Greek
thought, Mars is the god of strength and iron is dedicated to mars: thus
iron was used for weakness which is common in anaemia. [2]
In 1713, iron was shown to be present in blood. In the early 19th century, Blaud developed his famous Blaud’s pill consisting of ferrous sulphate and potassium carbonate for anaemia. [2]
1.3 IRON AND IRON SALTS
There are various forms
of iron present in oral formulations and they are: ferrous succinate
(35% iron), iron choline citrate, iron calcium complex (5% iron), ferric
ammonium citrate (scale iron), ferrous amminoate (10% iron), ferric
glycerophosphate, iron hydroxyl polymatose, ferrous fumarate (33% iron),
ferrous gluconate (12% iron), ferrous sulphate (hydrated salt 20% iron,
dried salt 30% iron) and colloidal ferric hydroxide (50% iron).[2]
Dissociable ferrous
salts are inexpensive, have high iron content and are better absorbed
than ferric salts, especially at higher doses. Ferrous sulphate tablet
which is an oral salt of iron is the cheapest and is sometimes preferred
in the treatment of iron deficiency on this account. [2]
Iron, forms the nucleus
of the iron-porphyrin haem ring which together with globin chain forms
haemoglobin. Haem is a tetrapyrrole and iron is at its centre.
Haemoglobin reversibly binds oxygen and provides the critical mechanism
for oxygen delivery from the lungs to other tissues. [3]
Iron is also an
essential component of myoglobin; haem enzymes such as the cytochromes,
catalase and peroxidase; and the metalloflavoprotein enzymes including
xanthine oxidase and the mitochondrial enzyme alpha-glycerophosphate
oxidase. [4]
1.4 IRON DEFICIENCY ANAEMIA AND TREATMENT
Iron deficiency anaemia
(microcytic hypochromic anaemia) as the name implies is the absence of
adequate iron, as a result of which small erythrocytes with insufficient
haemoglobin are formed. [3] Without enough iron, the body
uses up all its stored iron in the liver, bone marrow and other organs.
Once the stored iron is depleted, the body then makes very few red blood
cells resulting to Iron deficiency anaemia. [5]
A. CAUSES OF IRON DEFICIENCY ANEMIA
Iron deficiency anaemia
is usually caused by blood loss, poor diet and inadequate iron
absorption. The most common cause of iron deficiency in adult is blood
loss and the gastrointestinal tract is the common site of blood loss. [3]
B. CLINICAL PRESENTATION OF IRON DEFICIENCY ANAEMIA
In iron deficiency
anaemia, the erythrocyte mean cell volume (MCV) is less than 2273ml and
the mean cell haemoglobin concentration (MCHC) is low (less than 30%). [3]
Iron deficiency anaemia
leads to pallor, fatigue, dizziness, exertional dyspnea, and other
generalized symptoms of tissue hypoxia. There is also an unusual craving
for non-nutritive substances such as ice, dirt, paint or starch. Some
patients can also develop a strong urge to move the legs (the restless
legs syndrome). [5]
Iron deficiency can
affect metabolism in muscle independently of the effect of anaemia on
oxygen delivery. This may reflect a reduction in the activity of
iron-independent mitochondrial enzymes. [4]
C. CONSEQUENCES OF IRON DEFICIENCY ANAEMIA
Iron deficiency is the
most common cause of chronic anaemia. Iron deficiency has been
associated with behavioural and learning problems in children,
abnormalities in catecholamine metabolism and possibly impaired heat
production.
In infants and children,
there is impaired motor development and coordination, impaired language
development, decreased physical activity, psychological and behavioural
effects. [6]
In adults, there is decreased physical work and earning capacity and resistance to fatigue. [4]
In pregnant women, there
is increased maternal, fetal morbidity and mortality, as well as
increased low birth weight. Awareness of the ubiquitous role of iron
has stimulated considerable interest in the early and accurate detection
of iron deficiency and its prevention. [4]
D. POPULATION AT RISK FOR IRON DEFICIENCY ANAEMIA
Iron deficiency is
commonly seen in populations with increased iron requirements. These
include infants, especially premature infants; children during rapid
growth periods; pregnant and lactating women. [3] It is worth highlighting that the pregnant population is among the highest risk segment for iron deficiency. [7]
Iron deficiency can also be seen in patients with chronic kidney
diseases, who lose erythrocytes at a relatively high rate, and also form
them at a high rate as a result of treatment with the erythrocyte
growth factor, erythropoietin.
E. IRON DEFICIENCY ANAEMIA SCREENING TESTS. [6]
Several laboratory tests
can confirm the presence of iron deficiency anaemia. The most commonly
used are those that measure serum ferritin, transferrin saturation and
erythrocyte protoporphyrin.
Serum ferritin can be
measured by radioimmunoassay (RIA) or enzyme linked immunoassay (ELISA).
At all ages, a serum ferritin value of less than 10-12µg/L, indicates a
depletion of iron stores.
Transferrin saturation
is calculated by measuring both serum iron and total iron binding
capacity using spectrophotometric technique. The iron concentration is
divided by the iron binding capacity and multiplying by 100 to express
the result as a percentage. In adults, values below 16% is indicative of
iron deficiency, while for infants and children values below 12% and
14%, respectively, is indicative of iron deficiency.
Erythrocyte
protoporphyrin accumulates in red blood cells when it has insufficient
iron to combine with to form haem. It can be measured by a fluorescence
assay performed directly on a thin film of blood. If the value is higher
than 80µg/dl of red blood cells for children below the age of four and
70µg/dl for children above the age of four, then there is iron
deficiency anaemia.
F. PREVENTION OF IRON DEFICIENCY ANAEMIA. [6].
Approaches to its
prevention include; supplementation with medicinal iron, education and
associated measure to increase dietary iron intake and the control of
infection such as that caused by parasitic worms. Measures to increase
dietary iron intake include taking food such as liver, egg yolk etc.
which are very rich in iron. In the control of infection, there should
be provision of safe water, improvement in environmental sanitation and
personal hygiene. All these will help improve iron status.
G. TREATMENT OF IRON DEFICIENCY ANAEMIA
Food like liver, kidney, spinach, and
egg yolk are rich in iron, but sometimes it is necessary to supplement
the diet with “iron tablets”. [8] Iron deficiency anaemia is
therefore, treated with oral (ferrous sulphate tablet) or parenteral
iron preparations (iron dextran or iron sorbitol). Oral iron corrects
the anaemia just as rapidly and completely as parenteral iron in most
cases if, iron absorption from the gastrointestinal tract is normal. But
for patients with chronic kidney disease, parenteral iron
administration is preferred. [3]
In an iron-deficient
individual, about 50-100 mg of iron can be incorporated into haemoglobin
daily and about 25% of oral iron given as ferrous salt can be absorbed.
Therefore, 200-400mg of elemental iron should be given daily to correct
iron deficiency most rapidly. Treatment with oral iron should be
continued for 3-6 months after correction of the cause of the iron loss.
This corrects the anaemia and replenishes iron stores. [3]