Design,
Development and in-vitro evaluation
of Herbal Matrix tablet
NM Bhopale*, HS Sawarkar1, MB Narkhede1,
NV Thorat1, MR Bhise1 and SS Khadabadi2
1I.B.S.S.
2 Govt. College of Pharmacy, Amravati-444 603 (M.S.)
ABSTRACT
The
purpose of the present investigation was to develop the sustain release matrix
tablet of Tinospora cordifolia
using the various polymers like HPMC (Hydroxy-Propyl-methyl-cellulose), Ethyl cellulose (EC), of
different viscosity grade. Ethanolic extract of Tinospora cordifolia was used for the formulation
of sustain release matrix tablet and tablet formulations were developed by
using wet granulation method. Different diluents like lactose, magnesium stearate and cab-o-sil were used
for improving flowability and compressibility. Binder such as polyvinyl pyrrolidone was used for optimization of the formulations.
Sodium starch glycolate was used as disintegrating
agent. Pre and post formulation parameters were studied for all the batches.
HPMC –KM4 shows better result for matrix tablet in terms of sustain drug
release with comparison to different viscosity grade of HPMC and ethyl
cellulose. The dissolution study of the Tinospora cordifolia tablets exhibited 99.54% release of total polyphenol.
KEYWORDS:
Ethanolic extract of Tinospora cordifolia, HPMC, Ethyl cellulose,
Matrix tablet.
INTRODUCTION
Inflammation is the reaction of living tissue to
injury, infection, environmental agents, malignancy, and cellular changes. In
skin, inflammation is most visible because it causes noticeable swelling,
redness, discomfort and pain. The process leading to inflammation, which is
known as the inflammatory response, also induces changes that aren't seen but
influence the effects of inflammation and their severity1.
Studies on induced edema and arthritis and on human
arthritis proved the anti-inflammatory potency of the ethanolic extract of this
plant. Phase I and Phase II of adjuvant induced arthritis were also inhibited.
The anti-inflammatory activity of this plant resembles that of non-steroidal
anti-inflammatory agents2. It has weak antipyretic action and is a
morphine potentiator. The watery extract of the plant
is used as a febrifuge and is called “Indian Quinine”. The plant is used in
Ayurvedic rasayanas to improve the immune system and
the body's resistance to infections. The bitter principle present shows antiperiodic, antispasmodic, anti-inflammatory and
antipyretic properties.3. All the formulation containing Tinospora cordifolia
are present in conventional dosage forms which are prone to various problems like
fluctuation in drug blood level, patient’s inconvenience, etc. These problems can be overcome by formulating
sustain release tablet using ethanolic extract of Tinospora cordifolia root extract.
Material and
Methods:
HPMC (K4M, K15M, K100M), Ethyl cellulose (75cps,
100cps), and PVP (K30) were purchased from Loba chem.
(
Table no.1) Result of physical constants
|
Parameters
of physical constant |
%
w/w |
|
1)
Total Ash 2)
Acid insoluble ash 3)
Water soluble Ash 4)
Moisture content |
6.9
% 4.065
% 5.6
% 6.25
% |
|
Sr.
No. |
Chemical
tests performed |
WE |
|
1 |
Carbohydrates |
+ |
|
2 |
Proteins |
- |
|
3 |
Amino acids |
- |
|
4 |
Glycosides |
+ |
|
|
i)Anthraquinone |
+ |
|
ii)Cardiac |
- |
|
|
iii)Coumarins |
- |
|
|
iv)Cyanogenetic |
- |
|
|
5 |
Saponin glycosides |
+ |
|
6 |
Alkaloids: |
- |
|
7 |
Flavonoids: |
- |
|
8. |
Steroids and triterpenoids: |
- |
|
9. |
Tannins and phenolics |
+ |
|
10. |
Mucilage: |
+ |
|
11. |
Gums: |
- |
|
12. |
Fixed oil |
+ |
|
13. |
Volatile oil |
- |
Table no. 2) Extractive values of
different solvents, with percentage extractability and color of extract
|
Extract |
Extractive value % |
Colour of extract |
|
Water
soluble extractive |
7.6
% |
Reddish
black |
|
Ethanol
soluble extractive |
12.26
% |
Reddish
black |
Tinospora cordifolia was
obtained from local sources and authenticated by Dr. Prabha
Y. Bhogaonkar (Director, Government Vidarbha Institute of Science and Humanities,
Formulations of Tinospora cordifolia extract 5:
Tablets
of Tinospora cordifolia
root extract were prepared by wet granulation method. PVP-K30 (10%) and sodium
starch glycolate was added as binder and
disintegrating agent respectively. Matrix tablet were prepared by using
different viscosity grade HPMC and Ethyl cellulose. (Table
no.3).
The
extract, lactose and the polymer were passed through 60# sieve and then
granulated using PVP K-30 in isopropyl alcohol as granulating agent, the wet
mass was passed through 8# sieve. Granules were air dried for one hour and
dried granules were passed through 16# sieve. These granules were lubricated in
poly bag using talc and cab-o-sil. Desired quantity
of granules were weighed and fed manually to compression machine. The flat
faced punch i.e. upper punch with break line and plane lower punch of diameter
10 mm was used for compression.
Evaluation of Tinospora cordifolia tablet 6:
The
tablets of Tinospora cordifolia
extract were prepared by wet granulation method and evaluated for preformulation
parameters such as angle of repose, total porosity, Carr’s index, bulk density,
tap density and postformulation parameters like
friability, weight variation, hardness, disintegration were measured. (Table
no.4)
In-Vitro dissolution
study of Tinospora cordifolia tablet 7:
The in vitro
release of total polyphenol from formulation
batches was carried out in 0.1N HCl for 2 hours and
continued in pH 6.8 phosphate buffer for remaining 10 hours. The studies were
performed using USP dissolution apparatus II at 37 ± 0.5 °C and 50 rpm. Samples were taken at interval of
one hour each and analyzed for drug content at 765 nm. using
UV-Spectrophotometer.
Dissolution study was carried out for each 6 tablet per
batch for 12 hours and drug release study was carried out on the basis of total
polyphenol contents.
Table no. 3)
Results of phytochemical tests.
Table
no. 4) Formulation table showing composition of each matrix tablet using
various different polymers.
|
Formulation
code.Ţ Ingredients (mg)ß |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
|
Extract of Tinospora cordifolia |
250 |
250 |
250 |
250 |
250 |
250 |
|
HPMC-K-M4 |
32 |
- |
- |
- |
- |
- |
|
HPMC-K-M15 |
- |
32 |
- |
- |
- |
- |
|
HPMC-K-100M |
- |
- |
32 |
- |
- |
- |
|
E.C-75cps |
- |
- |
- |
30 |
- |
- |
|
E.C-100cps |
- |
- |
- |
- |
30 |
- |
|
S.S.G |
12 |
12 |
12 |
12 |
12 |
12 |
|
PVP-K-30 |
40 |
40 |
40 |
40 |
40 |
40 |
|
TALC |
10 |
10 |
10 |
10 |
10 |
10 |
|
CAB-O-SIL |
10 |
10 |
10 |
10 |
10 |
10 |
|
LACTOSE |
46 |
46 |
46 |
46 |
46 |
77 |
|
Tablet
weight (mg) |
400 |
400 |
400 |
400 |
400 |
400 |
Since, polyphenol constitutes
the major chemical entity in Tinospora cordifolia; we thought it logical to evaluate our formulation with
respect to total polyphenol content.
With respect to total polyphenol
contents present in extract, the drug release study was carried out. The
results of dissolution study were given in table no. 5.
Results and Discussion:
Extractive
values such as ethanol soluble extractive value was found to be 12.26% and
water soluble extractive value was found 7.6%. Ash values such as total ash,
acid insoluble ash, and water soluble ash were found to be 6.9%, 4.065 %, 5.6 %
respectively. Moisture content was found to be 6.25%. Total polyphenol
content was found to be 41.55% (Table no. 1, 2).
Fig. no.1) In
vitro release profile of all formulations showing sustains effect for
twelve hours.
Table no. 5)
Evaluation parameters of granules.
|
Parameters → Formulations ↓ |
Loose bulk density (LBD) |
Tapped bulk density (TBD) |
Carr’s index (I) |
Angle of Repose (Ө) |
Total Porosity |
|
F1 |
0.506 + 0.02 |
0.589 +0.036 |
14.89 +0.95 |
37.44 +0.12 |
27.43 +0.03 |
|
F2 |
0.290 +0.03 |
0.337+ 0.04 |
14.53 +0.05 |
37.02 +0.01 |
37.03 +0.04 |
|
F3 |
0.306 +0.02 |
0.351 +0.019 |
11.95 +0.33 |
37.72 +0.43 |
34.27 +0.02 |
|
F4 |
0.290 +0.04 |
0.338 +0.032 |
14.35 + 0.14 |
36.56 +0.01 |
37.03 0+.04 |
|
F5 |
0.309 +0.04 |
0.354 +0.023 |
13.11 +0.89 |
35.75 +1.68 |
31.25 +0.03 |
|
F6 |
0.509 + 0.002 |
0.579 +0.008 |
12.14 +0.94 |
36.89 +0.58 |
30.23 +0.02 |
Table no. 6)
Percent release profiles of formulations of Tinospora cordifolia extract containing HPMC and
ethyl cellulose
|
% released of Drug↓ |
||||||
|
Formulation code↓ |
||||||
|
Time(hrs) |
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
|
1 |
37.97 |
47.29 |
34.27 |
40.84 |
37.1 |
63.17 |
|
2 |
45.39 |
52.49 |
36.07 |
44.57 |
42.55 |
80.11 |
|
3 |
53.3 |
55.69 |
47.43 |
45.72 |
51.93 |
97.54 |
|
4 |
60.36 |
59.46 |
49.33 |
47.43 |
52.34 |
_ |
|
5 |
63.17 |
61.7 |
53.09 |
49.12 |
53.93 |
_ |
|
6 |
67.07 |
66.18 |
53.81 |
49.72 |
61.32 |
_ |
|
7 |
70.99 |
68.66 |
54.39 |
62.42 |
66.66 |
_ |
|
8 |
72.73 |
74.43 |
58.79 |
65.43 |
72.34 |
_ |
|
9 |
80.11 |
78.5 |
59.9 |
70.13 |
82.86 |
_ |
|
10 |
80.14 |
95.61 |
60.46 |
72.85 |
83.05 |
_ |
|
11 |
83.79 |
97.36 |
61.11 |
73.01 |
86.25 |
_ |
|
12 |
97.54 |
97.38 |
70.1 |
73.04 |
87.09 |
_ |
Phytochemical
study ethanol extract of Tinospora cordifolia
were shows presence of carbohydrates, glycosides, anthraquinone,
saponin glycosides, tannins and phenolics,
mucilage and fixed oil (Table no. 3).
Since, polyphenol constitute
are major chemical entity in Tinospora cordifolia, we thought it logical to evaluate our formulation with
respect to total polyphenol content. Polyphenol content can be taken as a reliable and
reproducible parameter for the dissolution study of the Tinospora cordifolia formulation.
In
the current research work an attempt was made to formulate a matrix tablet of Tinospora cordifolia
extract. From the results it can be concluded that, the matrix tablet prepared
using by using ethanolic extracts of Tinospora cordifolia is found to be a novel one. Sustain release matrix tablets of Tinospora cordifolia
were prepared successfully using EC and HPMC as release retarding polymers by
wet granulation method (Table no 4).
Various evaluation parameter for the granules like bulk density, tap density,
angle of repose, total porosity and Carr’s index suggest that granules has good
flow property (Table no 5).
Various evaluation parameters for tablets like thickness, hardness, friability
and disintegration of all formulations were found to be satisfactory. In case
of formulations containing HPMC, viscosity was a major factor affecting the
drug release. An inverse relationship
existed between polymer viscosity and drug release; thus higher the polymer
viscosity lower was the drug release. From
the dissolution study it was found that HPMC K4M shows better drug release, as
compared to other polymers (Table no 6).
CONCLUSION:
Present research work deals with the formulation and
evaluation of matrix tablet. Tinospora cordifolia root were purchased from the local market of
Nagpur.
Dr.
Prabha Y. Bhogaonkar,
Director, Vidarbha Institute of Science and
Humanities had done the authentication of Tinospora cordifolia Linn.
Various
Physical parameters like, Total ash,
Water soluble ash, Acid insoluble ash, LOD, Water soluble extractive value,
Ethanol soluble extractive value of Tinospora cordifolia were determined.
Various
qualitative tests for inorganic elements like Aluminum, Chloride, and Copper
etc. were determined.
Ethanolic
extract of root of Tinospora
cordifolia was prepared and this extract was
tested for presence of various Phytochemicals like
Carbohydrates, Proteins, Alkaloids, Glycosides, etc.
Formulations were prepared by using ethanol root extract
of Tinospora cordifolia
and various sustained release polymers.
The
granules were prepared by using Wet granulation method and evaluated for
various parameters i.e. Bulk density, % Compressibility index, Angle of repose and
Total porosity. These granules were then compressed into tablet and evaluated
for various parameters i.e. Thickness, Hardness, Weight variation, Friability,
Disintegration time. All these formulations passed the criteria of IP.
In
case of formulations containing HPMC, viscosity was a major factor affecting
the drug release. An inverse relationship existed between polymer viscosity and
drug release; thus higher the polymer viscosity lower was the drug release.
From
the results it can be concluded that, the Matrix Tablet prepared using extracts
of Tinospora cordifolia
is found to be a novel one.
References:
1)
R. S. Satoskar, S. D. Bhandarkar,
Pharmacology and pharmacotherapeutics, 9th
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2)
Pendse, V. K., M. M. Mahawar, N.
K. Khanna, K. C. Somani and
S. K. Gautam, Anti-inflammatory and related activity
of water extract of Tinospora cordifolia,
1981, Indian Drugs 19, 1, 14--21.
3)
Dr. K.M. Nadkarni, The Indian Materia
Medica, Vol.I, pg 1220-1221
4)
Quality standards
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Received on 04.09.2009
Accepted on 07.11.2009
© A&V Publication all right reserved
Research Journal of Pharmaceutical
Dosage Forms and Technology.
1(3): Nov. – Dec. 2009, 254-256