ISSN: 2277- 7695

CODEN Code: PIHNBQ

ZDB-Number: 2663038-2
IC Journal No: 7725

Vol. 2 No. 5 2013

Online Available at www.thepharmajournal.com

THE PHARMA INNOVATION - JOURNAL

Formulation and Evaluation of Herbal Anti-diabetic
Formulation Containing Eugenia jambolana, Gymnema
sylvestre, Tinospora cordifolia, Pterocarpus marscipum,
Terminalia bellerica & Emblica officinalis
Ritesh Arora 1*, Anuj Mittal 1, Keshari Kishore Jha 1
1.

Teerthanker Mahaveer College of Pharmacy, TMU, Moradabad

[E-mail: cool.ritesharora@gmail.com]

Diabetes mellitus is the commonest endocrine disorder that affects more than 100 million people worldwide (6% of
the population). It is caused by the deficiency or ineffective production of insulin by pancreas which result in
increase or decrease in concentration of glucose in the blood. Due to various drawbacks of synthetic antidiabetic
drugs there is a continuous search for alternative therapy in diabetes. Many herbal plants with hypoglycemic
properties are known for a long time and they are used traditionally in India. Present study was conducted to
formulate a suitable dosage form and used traditionally such as Eugenia jambolana, Gymnema sylvestre, Tinospora
cordifolia, Pterocarpus marscipum, Terminalia bellerica are most of the effective and the most commonly studied
Indian plants in relation to diabetes.
Keyword: Diabetes Mellitus, Hypoglycaemic, Herbal Medicines, Allopathic Drugs, Ayurveda.

1. Introduction
The word diabetes was coined by the Greek
physician Aretaeus in the first century AD
Diabetes mellitus has been known since ages and
sweetness of urine has been mentioned in
Ayurveda by Sushruta. Its pharmacotherapy is 80
year old. The presence of sugar in the urine of
diabetics was demonstrated by Dobson in 1755[1].
Diabetes mellitus is a clinical syndrome
characterized by inappropriate hyperglycemia
caused by a relative or absolute deficiency of
insulin or by a resistance to the action of insulin
at cellular level. It is the most common endocrine
disorder, affecting 100 million individuals
worldwide[2].
Insulin is polypeptide hormone produced by the
-cells of islets of Langerhans of pancreas and is
main key for metabolism of carbohydrate, fats
Vol. 2 No. 5 2013

and proteins. It is anabolic hormone and promotes

synthesis of glycogen, tricylglycerols and
proteins. Human insulin has molecular weight
5734 and contains 51 amino acid in two
polypeptides chains. The chain A has 21 amino
acids and chain B has 30 amino acids. These
chains held together by two inter chain disulfide
bridges[3]. Acute complications include diabetic
ketoacidosis, nonketotic hyperosmolar coma, and
diabetic coma. In case of chronic complication,
chronic elevation of blood glucose level leads to
damage to blood vessels. In diabetes, the resultant
problems are grouped under "micro vascular
disease (due to damage to small blood vessels)
and "macro vascular disease" (due to damage to
the arteries)[4].
There are different approaches to the treatment of
diabetes, like insulin treatment in type 1 diabetes:

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Sulphonylureas, which release insulin from

pancreas by blocking the ATP-sensitive
potassium channels[5]; Biguanides which decrease
the insulin resistance; Thiazolidinediones, which
increase the insulin sensitivity; alpha-glucosidase
inhibitors like acarbose which decrease glucose
absorption from intestine, thereby decreasing
postprandial hyperglycemia; meglitinides like
rapaglinide which are insulin secretogoues.
Traditional herbal mineral plays an important part
in the treatment of diabetes. If research was able
to even identify some 5-6 herbal drugs that can
reduce dose of insulin by increasing resistance
sensitivity, reducing insulin resistance, then it is
possibly contributes in the treatment of diabetes.
Herbal medicines are often used as therapeutic
remedies in combination with allopathic drugs[6].
1.1 Etiology of Diabetes, Cure and Strategy
Diabetic patients are diagnosed by blood or
urinary glucose measurement through different
techniques. On the basis of etiology DM
(Diabetes mellitus) are categories mainly two
types viz:
1. Primary Diabetes (Type I or Insulin
Dependent Diabetes Mellitus).
2. Secondary Diabetes (Type II or Non
insulin Dependent Diabetes Mellitus).
Primary DM (Diabetes mellitus) clinically
dependent on insulin due to there is decrease in
the number of -cells in the islets of Langerhans
and thus there is absolute deficiency of insulin
hence this is known as Insulin Dependent
Diabetes Mellitus (IDDM) or Type I. The main
treatment for this Type I of DM (Diabetes
mellitus) is insulin.
Secondary DM (Diabetes mellitus) is referred as
Type II or Non Insulin Dependent Diabetes
Mellitus (NIDDM) because these types of
patients are insulin resistances as well as loss of
insulin secretion contributes to the onset of
disease. The patients are usually obese and the
treatment
is
usually
dietary,
through
[7]
supplementary oral hypoglycemic drugs .
1.2 Strategy for Treatment of Diabetes
Basic therapeutic approach to treat diabetes may
be to inhibit the absorption of glucose by
Vol. 2 No. 5 2013

retarding the action of gastrointestinal enzymes

such as -glucosidase and -amylase. Because
the complication of disease is mainly due to the
higher glucose level in blood which dysfunction
the other organs of body. Thus we can say that
the effective -glucosidase inhibitors may serves
as chemotherapeutic agents for clinic use in the
treatment of diabetes and obesity[8].
1.3 Medicine for Treatment of Diabetes
Mellitus
1.3.1. Insulin
Insulin increases glucose uptake in cells by
stimulating the translocation of the glucose
transporter GLUT4 from intracellular sites to the
cell surface[9]. Insulin circulates in blood as the
free monomer and its half life in plasma is about
5 - 6 min in normal subjects. Although glucose is
the principal stimulus to insulin secretion in
human beings, this process is tightly regulated by
the coordinated of nutrients, gastrointestinal and
pancreatic
hormones
and
autonomic
neurotransmitters[10]. The main drawback of
insulin is taken through injection.
1.3.2. Oral Hypoglycemic Drugs
Oral Hypoglycemic drugs are those drugs that
lower blood glucose level and taken orally. These
drugs are synthetic and complex organic
substances. Hence the search for oral active drugs
is in demand.
1) Sulphonylureas Drugs
i.
First Generation Drugs
a. Tolbutamide;
b. Chlorpropamide;
ii.
Second Generation Drugs
a) Glibenclamide;
b) Glipizide;
c) Gliclazide.
2) Biguanides
a) Phenformin;
b) Metformin.
3) Meglitinide / Phenyl alanine analogues
a) Repaglinide
b) Nateglinide

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aqueous extract of Gymnema sylvestre leaves

stimulate -cell regeneration by proliferation of
its precursor or cells in the pancreatic duct[15].

4) Thiazolidinediones
a) Rosiglitazone
b) Pioglitazone
5) alpha-glucosidase inhibitors
a) Acarbose;
b) Miglitol.
These drugs are effective in diabetes but having
some limitations such as hypoglycemia occurs
with regular use of sulfonylurea compounds but
occurrences are much fewer than with insulin
therapy. It is prescribed by doctors that biguanids
should not use in patients with renal diseases. On
the other hand the main side effect of Acarbose is
flatulence[11].
1.3.3. Herbal Drugs
There are many herbal products/herbal extracts
are reported to treat the diabetes mellitus, we can
classify these drugs according to their mode of
action as:
1.3.3.1. Extracts/Drugs Act as -Glucosidase
or -Amylase Inhibitor
These types of drugs/extracts are able to reduce
the blood glucose level by inhibiting the gastric
enzymes which is obligatory for the break the
polysaccharides in to the simple sugar.
The aqueous and methanolic extract of Syzgium
cumini (seed) and Pisidium guajava (leaves)
shows -amylase inhibition[12]; while Rhus
verniciflua stem screened for -glucosidase
inhibition effect mixture of methanol and ethanol
extract shows the potent inhibition of glucosidase enzyme[13]. There are large number
of plants which have the capability to inhibit the
-glucosidase and -amylase activity and may be
used as treatment of diabetes Type I and Type II.
1.3.3.2. Extracts/Drugs Increases Insulin
Secretion or -Cell Regeneration
These types of drugs are directly concern with the
Type I or IDDM diabetes which are disable to
secreting the less or few amount of insulin.
Radix of Acorus calamus is used as in the therapy
of diabetes in traditional folk medicine of
America and Indonesia, this sensitize the insulin
activity of its ethyl acetate extract[14]. Moreover
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1.3.3.3. Extracts/Drugs Act as Hypoglycemic,

Anti-hyperglycemic or Antidiabetic Effect
These classes of herbal drugs reduce the blood
glucose level directly, this may be also used to
treat the both type of diabetes mellitus (IDDM
and NIDDM).
Mangifera indica Linn. (Locally known as mango
tree) has antidiabetic property, ethanolic and
water extract of leaves and stem bark of
Mangifera indica shows significant antihyperglycemic effect[16]. Tinospora cordifolia
stem extract show antidiabetic and ameliorative
activity[17].
1.3.3.4. Extracts/Drugs Dealing with the
Complications of Diabetes Mellitus
Diabetes mellitus is metabolic syndrome
characterized by deregulation in carbohydrate
metabolism associated with defect in insulin
secretion or action by which glucose level of
blood increases, the different type of
complication occurred. To treat these type of
problem many herbal drugs/extract may play a
key role.
The aqueous extract of fruit of Terminalia
bellerica Roxb reduces oxidative stress in Type II
diabetes mice model[18]. Oral administrations of
Coccinia indica leaf extract (200 mg/kg body
weight) for 45 days significantly reduce the
thiobarbituric acid reactive substances and
hydroperoxides. The extract also causes a
significant increase in reduced glutathione,
superoxide dismutase, catalase, glutathione
peroxidase and glutathione-S-transferase in liver
and kidney of streptozotocin diabetic rats, which
clearly shows the antioxidant property[19].
2. Materials and Methods
Dried herbal plants were collected from the
Gaumukh Pharmaceuticals Sonepat, Haryana,
India. Prior to the commencement of the
experiment, all the drugs were placed to the new
environmental condition for a period of one week
to remove moisture from the herbal drug. During

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the experimental period, the drugs were kept in a

well ventilated laboratory at room temperature of

25 Co.

2.1 Plant Materials and Excipients used in the formulation

S. No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

Chemical name
Amla (Emblica officinalis)
Gymnema (Gymnema sylvestre)
Giloe (Tinospora cordifolia)
Baheda (Terminalia bellerica)
Jamun (Eugenia jambolana)
Pterocarpus (Pterocarpus marsupium)
Aspartame
Citric acid monoanhydrate
Sodium phosphate, dibasic
Benzoic acid
Sodium benzoate
HPMC

2.2 Experimental Formulation Design:2.2.1. Preparation of Formulation

Formulation is a process to access the route for
the preparation leads to come out a product
named as formulation. In the formulation, the
concentrations of the ingredients are well defined
in the documentation to prevent the errors and
weigh in the quantity as required or specified.
There are various steps involved in the
formulation of syrup are as follows:1. Extraction of crude drug
2. Preparation of citrate-phosphate buffer pH
4.2
3. Preparation of syrup base
4. Preparation of final formulation.
1. Extraction of Crude Drugs by using
Percolation method
Step 1. (Size Reduction):- The drug was
subjected to suitable degree of size reduction,
usually from coarse powder to fine powder,
increased the surface area of drug, for uniform
packing of the percolator, to slow down the
movement of the menstruum.
Step 2. (Imbibation):- During imbibation the
powdered drug was moistened with a suitable
amount of menstruum and allowed standing for
Vol. 2 No. 5 2013

Company name
Gaumukh Pharmaceuticals, Sonepath
Gaumukh Pharmaceuticals, Sonepath
Gaumukh Pharmaceuticals, Sonepath
Gaumukh Pharmaceuticals, Sonepath
Gaumukh Pharmaceuticals, Sonepath
Gaumukh Pharmaceuticals, Sonepath
CDH Laboratory Reagent
CDH Laboratory Reagent
Fisher scientific
Rankem Laboratory Reagent
Rankem Laboratory Reagent
CDH Laboratory Reagent

some hours in a closed container. During this

period the drug swelled up and menstruum
penetrated the cell walls. After the lapse of time,
the moistened drug was passed through a coarse
sieve to remove the lumps and mixed the dry
powder, if any.
Step 3. (Packing):- After imbibation the
moistened drug was evenly packed into a
percolator. In a percolator, glass wool was placed
on false bottom to support the column of the drug
and help in the escape of the percolate. A small
amount of moistened drug was introduced in the
percolator and pressed lightly with glass rod to
give even compression. Similarly, more of
moistened drug was introduced and pressed till
whole of the drug packed in the percolator. After
suitable packing of the drug a piece of filter paper
was placed over top of it on which small quantity
of purified sand was placed to prevent
disturbances of the packed material.
Step 4. (Maceration):- After packing the
column, sufficient menstruum was added to
saturate the material and top of the percolator
covered with a lid. The tap fitted at the bottom of
percolator was closed. More amount of
menstruum was allowed to add at the top to
maintain a layer of menstruum over the drug. The

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percolator kept aside for 24 hours to macerate the

drug.
Step 5. (Percolation):- After 24 hours
maceration of the drug, the lower tap of the
percolator was opened and liquid was collected in
a container until 3/4th volume of the finished
product is obtained. Marc was allowed to press
for the complete removal of menstruum and
placed in a closed container.
Drying of extract- The aqueous extract obtained
from the process of extraction i.e. percolation was
concentrated by allowing the solvent evaporation
of the extract using water bath.
After complete evaporation, dried drug extract
was stored in a well closed container to prevent
the growth of moulds and microorganisms[20].
2. Preparation of citrate-phosphate buffer pH
4.2:- Citrate phosphate buffer was prepared
by mixing the freshly prepared standard
solution of citric acid (0.1M) and dibasic
sodium phosphate (0.2M) as specified in the
table below as per pH required.
(a) 0.1 M Citric acid; 19.21 g/l (M.W. 192.1)
(b) 0.2 M Dibasic sodium phosphate; 35.6 g/l
(dihydrate; M.W. 178.0)
Mix citric acid and sodium phosphate solutions in
the proportions indicated and adjusted the final
volume to 100 ml with deionized water. The final
pH was adjusted using a sensitive pH meter[21].

S. no.

Ingredients

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

Giloe
Gymnema
Jamun
Pterocarpus
Baheda
Amla
HPMC
Sodium benzoate
Benzoic acid
Aspartame
Syrup base

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pH
Vol. of citric acid
Vol. of dibasic sodium phosphate

4.2
29.4
20.6

Prepared citrate-phosphate buffer pH 4.2 was

sterilized in autoclave and placed in well closed
container until used.
3. Preparation of syrup base- Syrup base is a
mixture of ingredients containing inert
substances (other than the drugs having
therapeutic
action)
i.e.
sweetners,
preservatives, flavors, viscous agents, etc
Firstly, buffer of 40mL was freshly prepared and
viscosity enhancer such as HPMC (5%w/v) was
dispersed with vigorous shaking. This mixture
solution of HPMC was allowed to sterile in
autoclave.
4. Preparation of syrup- All the active
ingredients, sweeteners and preservatives
weighed as specified in the formulation table
and allowed to dissolve in 10mL distilled
water with vigorous shaking until the clear
solution not prepared. Then, 40mL of buffer
solution and 10mL of aqueous solution was
mixed properly. The prepared solution was
used to formulate and got sterile in the
autoclave.
2.2.2 Formulations:
Three formulations were prepared according to
their concentration specified in the table below
and named as F1, F2 & F3.

Concentration (per 50mL)

F1
F2
F3
100mg
50mg
150mg
100mg
150mg
50mg
75mg
100mg
50mg
75mg
50mg
100mg
35mg
35mg
35mg
40mg
40mg
40mg
2.5gm (5%)
100mg (0.2%)
150mg (0.3%)
200mg (0.4%)
50mg (0.1%)
250mg (0.5%)
q.s. to 50mL

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3. Result & Discussion

All formulations showed dark color due to plant
extract. The pH of formulation (F1, F2 and F3)
varies from 4.13-4.25 may be due to varied
percentage of acidic or basic compounds present
in the aqueous extract.
The % sedimentation of each formulation (F1,
F2, and F3) varies from 1-1.5% may be due to
Formulation/
Parameter
Color
Odour
pH
% Sedimentation
Microbial Test
Viscosity

F1

F2

F3

Dark brown
pungent
4.13
1%
pass
52.6 mPa

Dark brown
pungent
4.21
1%
pass
51.3mPa

Dark brown
pungent
4.25
1.5%
pass
50.7mPa

4. Stability study- The results inferred that the

formulation F1 was failed in the sterility test
while other formulations were remained
unchanged at 40C. Thus the effective
concentration of preservative must be NLT
0.3%w/v.
5. Conclusion
The present worker concluded that the
formulations containing multiple aqueous herbal
extracts using aspartame as sweetener for diabetic
patients was successfully prepared and found
stable at 40C. The formulations prepared are
unique in it containing natural anti-oxidants for
the oxidizable part of extracts. The drugs using in
the formulation i.e. Emblica officinalis,
Tinospora cordifolia, Gymnema sylvestre,
Terminalia bellerica, Eugenia jambolana,
Pterocarpus marscipum may exhibit anti-diabetic
activity on alloxan induced diabetic rat as per
given literature. There is increasing demand by
patients to use the natural products with
antidiabetic activity. In recent times there has
been renewed interest in the plant remedied.
Plants hold definite promises in the management
of diabetes mellitus. Here the present worker
creates a thrust for the future researchers to
standardize the selected formulation for better
optimization that can play a significant role in
improving the hypoglycemic action.

Vol. 2 No. 5 2013

difference in the concentration of different

aqueous extracts.
Microbial test was conducted for all three
formulations and results inferred that the
formulations were sterile, No growth were seen
thus passed the test.
The viscosity of formulation (F1, F2 and F3)
varies from 50.7-56.6.

6. Acknowledgement:
I would like to express my deep gratitude to Mr.
Suresh Jain, Chancellor, TMU and Prof. R. K.
Mittal, Vice-Chancellor for providing the
required facility in campus, for their guidance,
enthusiastic encouragement and useful critiques
of this research work. I would also like to extend
my thanks to the technicians of the laboratory of
the Pharmaceutics department for their valuable
help.
Finally, I wish to thank my parents for their
support and encouragement throughout my study.
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