Formulation, Evaluation and Optimization of Fast Disintegrating Nifedipine 20 mg tablet by using Super Disintegrants

International Journal of Scientific Research and Engineering Development-– Volume 2 Issue 4, July – Aug 2019
Available at www.ijsred.com
ISSN : 2581-7175 ©IJSRED: All Rights are Reserved Page 430
Formulation, Evaluation and Optimization of Fast Disintegrating
Nifedipine 20 mg tablet by using Super Disintegrants
*Jameel Abbas1
, Patel Huzaifa2
, Z.E. Inamdar3
, Mohd Farooque4
, Makrani Shahrukh5
, Dr.
Sadequa Parveen6
, Dr. Shaikh Muzaffar Ahmed7
1,4
UBKWT’s D. Pharmacy college, Kunjkheda, Dist. Aurangabad. Maharashtra. India
2,3
Jamia college of Pharmacy, akkalkuwa, Dist. Nandurbar. Maharashtra. India
5
Ali Allana college of Pharmacy, akkalkuwa, Dist. Nandurbar. Maharashtra. India
6
Yunus Fazlani Unani Medical Collage, Kunjkheda, Dist. Aurangabad, India
7
Ahmed Garib Unani Medical Collage. Akkalkuwa, Dist. Nandurbar. Maharashtra. India
________________________________________________________________________________________________________
Abstract
Tablet among the all dosage form is the common one and in the Pharmacy it is the mother of Pharmacy. Generally tablet are
accepted in all category of patient. In children Dispersible form and in female for virginal infection virginal form are the preferred.
The most common preferred route is oral rout of administration. In ancient Ayurveda, Unani, Greek, Egyptian remedies drug in
the form of Churna, Bhasma, Gutika, Araka, are administered though oral rout. Pills which are coated by natural resinous material
are administered in the form of tablet through oral rout.
Today oro-dispersible tablet from novel drug delivery system gain importance from patient. Which is administer to the patient
to control the various immediate action viz. attack of angina or hypertension in cardiac problems. Orodispersible tablet gets
dispersed in oral cavity in absence of water and release fast drug which result fast pharmacological action. In the market drug from
Analgesic, Antipyretic, Antihypertensive and many more are available in the form of the orodispersible tablet. Various
manufacture are formulated this formulation by various method. The most importance thing in this formulation are masking of
taste of drugs. Generally oro-dispersible tablet are prepared by direct compression method. Dry granulation, wet granulation, Spry
drying is the various methods for preparation of oro-dispersible tablet. Oro-dispersible tablet generally contains filler, glidant, anti-
adherent super disintegrate, Flavoring agent sweetener and resins. Evaluation parameter includes hardness, friability, wetting time,
moisture uptake, disintegration test, and dissolution test. Wetting time, Disintegration time, and Dissolution test is directly
proportional to the hydrophobic ingredient added for lubrication, anti-adherent, Glidant action. These hydrophobic ingredient are
Magnesium Stearate. To oppose the action of magnesium stearate, hydrophilic additives are incorporated viz Sodium lauryl
sulphate.
From Marketing point of view special Marketing Executive team required to promote the new technique , new formulation with
demonstration to the Cardiac Surgeon, Pediatrics, Orthopedics, Gynecologists, Ophthalmologists, Urologist. After demonstration
that how to use the Orodispersible tablet these marketing team personally serve to the new admitted patients.
Keywords: Oro-dispersible tablet, wetting time, Dissolution test
1. INTRODUCTION
Quality are built in the pharmaceutical formulation by design the formulation. The total quality in the product are known as
Total Quality Management. To gain this goal of optimized quality product, the knowledge obtained from pharmaceutical
development studies and manufacturing provides the scientific background. Although it is based on different pharmaceutical
studies, but it has its aim that it minimizes the end product testing and Increases the chances of regulatory acceptance by
different pharmaceutical governing bodies. The aim and objective of the present study is to develop and evaluate oro dispersible
tablet of Nifedipine and enhance the onset of action of Nifedipine and also to study the influence of excipients on the physical
characteristics of the tablets by applying two level three factor factorial designs taking Nifedipine as model drug which is used
in the treatment of the Hypertension, Angina Pectoris, cardiac arrhythmia. The study of this formulation to select the best
possible excipient combination of semi synthetic & natural and artificial additives to development of formulation. Super
disintegrants viz Cross carmillose sodium are added to formulate the dispersible tablets among all the diluents and disintegrants
used. Finally the effect of the additives or various excipients ratio and super disintegrants on various properties of the tablet
were also determined.
2. MATERIAL AND METHOD
2.1 API Structure Characterization:
Formula : C17H18N2O6
Molar mass : 345.335 g / mol
Melting point : 172 to 174 ºC
RESEARCH ARTICLE OPEN ACCESS

Nifedipine was patented in 1967 and approved for use in the United States of America in 1981. It is on the World Health
Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system for various cardiac
diseases. It is available as a generic medication in various dosage form and various formulation range from 5 mg to 20 mg.
Nifedipine is odorless, yellow crystalline tasteless Powder. Nifedipine is water insoluble. Chemically Nifedipine is a
Dihydropyridine Calcium Channel Blocker. The mechanism of action of Nifedipine on heart is as a Calcium Channel Antagonist.
The chemical classification of Nifedipine is Dihydropyridine. Nifedipine is a first generation calcium channel blocker used to treat
hypertension and angina pectoris and other cardiovascular diseases. Nifedipine therapy is associated with a low rate of serum
enzyme elevations and has been linked to several instances of clinically apparent acute liver injury. Nifedipine is a potent
vasodilator agent with calcium antagonistic action. It is a useful anti-angina agent that also lowers blood pressure and
hypertension.
IUPAC Name
Dimethyl 2, 6-dimethyl-4-(2-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate.
2.2 Pre formulation Studies:
Drug Solubility:
As per the research study from the Nifedipine Wikipedia the Solubility of the drug at 20º C (g/L): acetone 250, methylene chloride
160, chloroform 140, ethyl acetate 50, methanol 26, ethanol 17. But practically we found the solubility of Nifedipine was checked
in different solvents which are shown in following table.
Sr. No. Solvents / Chemicals Mg/ ml
1 Water 0.001
2 Ethanol 12.5
3 Chloroform 76.25
4 Acetone 295.5
5 Hydrochloric Acid 0.1 N 0.025
2.3 Drug and Excipients studies:
S. No. Drug+ Excipients Duration (months) Results
1 Nifedipine + Starch 6 Months Stable
2 Nifedipine + Talcum 6 Months Stable
3 Nifedipine + Mag. Stearate 6 Months Stable
4 Nifedipine +MCCP 6 Months Stable
5 Nifedipine +Lactose 6 Months Stable
6 Nifedipine +CCS 6 Months Stable
7 Nifedipine +Saccharine 6 Months Stable
8 Nifedipine +DC starch 6 Months Stable
9 Nifedipine + SSG 6 Months Stable
10 Nifedipine + Mannitol 6 Months Stable

2.4 MATERIAL AND THEIR USE WITH OBTAINED SOURCE
Sr.
No.
Material Uses of Ingredients Sources
1 Nifedipine Active Ingredients J.B. Chemicals
Ankaleshwer. Bharuch.
2 Starch DC Grade Diluents Pacific India.
A Pharmaceutical
Exporter,
Villalge: Dhana,
Baghbania.
Nalagarh. Solan.
Himachal Pardesh
3 Lactose Diluents/ Filler
4 Cross Carmillose Sod. Super disintegrants
5 Talcum Lubricants
6 Magnesium Stearate Glidant
7 Mannitol Filler/ Sweetener
8 Aspartame Sweetener
9 Micro crystalline cellulose Diluents / filler
2.5 Preparation of Nifedipine 20 mg tablet by direct compression method.
Formulation table.
Serial
No.
Ingredients C1
(mg)
C2
(mg)
C3
(mg)
C4
(mg)
C5
(mg)
1 Nifedipine 20 20 20 20 20
2 Starch DC 140 140 140 140 140
3 Lactose 120 124 128 132 136
4 Mannitol 60 60 60 60 60
5 Aspartame 10 10 10 10 10
6 Talcum 10 10 10 10 10
7 Mag. Stearate 5 5 5 5 5
8 Cross Carmillose sodium 20 16 12 8 4
9 SSG 15 15 15 15 15
Total wright 400 400 400 400 400
All the ingredients viz active ingredients, additives were passed through 60 # sieve separately, Magnesium stearate & Talc through
40 #. Then the ingredients were weighed and mixed in double dilution order or Geometric mixing and tablets were compressed
with 7 mm sizes biconvex round punch to get tablet using Rimek double rotary Compression Machine. In the following
diagrammed showing the granules prepared by direct missing for direct compression.
FLOW CHART OF DIRECT
COMPRESSION
NIFEDIPINE 20 mg ODT GRANULES FOR
COMPRESSION

3. Post compression Parameters:
3.1 Thickness of compressed tablet.
The thickness of the compress tablets of Nifedipine was determined using a Digital Vernier calliper. Ten tablets from each type of
formulation were used and average values were calculated. It is expressed in mm.
3.2 Hardness
The resistance of tablets during passing through hopper, Blister Cartooning, breakage, under conditions of storage, transportation
and Handling before usage are directly proportional to its hardness. For each formulation, the hardness of 6 tablets was determined
using the Pfizer Hardener Tester and Monsanto hardness tester. The tablet was held along its oblong axis in Between the two jaws
of the tester. At this point, reading should be zero kg/cm2
. Then constant force was applied by rotating the knob in Monsanto tester
and in case of Pfizer directly force applied until the tablet breakdown in the pieces. The reading the both cases at this point was
noted.
3.3 Friability Test:
Friability Test is generally used the measure of tablet strength. Roche Friability tester was used for testing the friability using. In
This test subjects a number of compressed tablets to the combined effect of shock abrasion by utilizing a circular plastic chamber
which revolves at a speed of 25 revolution per minutes for 4 minutes i.e. 100 rpm, dropping the compressed tablets of Nifedipine
to a distance of 6 inches in each revolution. A sample of weighed 6 compressed tablets of was placed in Roche friability chamber
which was then operated for 100 revolutions i.e. 4 minutes. The tablets were then de-dusted, and broken tablet are removed and
reweighed. A loss of less than 1 % in weight in generally considered acceptable according to Pharmacopeia. Percentage friability
(% F) was calculated as follows:
% Friability = Initial Weight – Final Weight X 100
Initial Weight
3.4 Weight variation test:
As per the limitation of Pharmacopeia to find out weight variation test, 20 tablets of each type of formulation were weighed
individually using single pan balance or an electronic balance, average weight was calculated and individual tablet weight was
then compared with average value to find the deviation in weight.
Specifications for tablets as per Indian Pharmacopeia. 1996.
Percentage Deviation Average Weight of Tablet
(mg)
1 10 80 mg or less
2 7.5 More than 80 mg but less that 250 mg
3 5 250 or more
3.5. Uniformity of drug content:
Five tablets of each compression formulation are weighed and crushed in mortar Pastel and powder, or crushed equivalent to 10
mg of Nifedipine was weighed and dissolved in 100 ml of 0.1N Hydrochloric acid (pH 1.2). This was the stock solution from
which 0.2 ml sample was withdrawn and diluted to 10 ml with 0.1N Hydrochloric acid. The absorbance was measured at
wavelength 237.5 nm using double beam Ultra Violet Visible spectro photometer. Content uniformity of the drug was calculated
using formula.
% Purity of the Drug = 10 C (Au / As) -------

Where, C = Concentration,
Au and As=Absorbance’s obtained from unknown preparation and standard Preparation.
3.6. Wetting time:
This method is applied to calculate tablet wetting time. A piece of tissue paper or absorbent folded twice was placed in a small
Glass Petri dish having the diameter 6.5 cm, containing 10 ml of water. Compressed tablet was placed on the paper, and the time
record or note for complete wetting. Three trials for each batch were performed and standard deviation are calculated.
3.7. In vitro disintegration time:
The process of breakdown or convert the tablet into pieces or into smaller particles is called as disintegration. The in vitro
Disintegration time of a tablet was determined using disintegration test apparatus as per Indian Pharmacopeia specifications. Place
one tablet in each of the 6 tubes of the basket. Add a disc to each tube and run the apparatus using distilled water maintained at 37°
± 2°C which is similar to body temperature. The assembly should be raised and lowered between 30 cycles per minute in the 0.1 N
HCL or Distilled water maintained at 37° ± 2°C. The time in seconds taken for complete disintegration of the tablet.
In this disintegration test if the tablet are adhere to the 10 # sieve then continue the test till all tablet are completely disintegrated.
3.8. In vitro dissolution test:
Rate of dissolution are studied by using USP type-II apparatus having 50 rpm, using 900ml of 0.1 N Hydrochloric acid as
dissolution solvent. Temperature of the dissolution medium was maintained at 37 ± 0.5°C. The sample of dissolution medium was
withdrawn at every 5 min interval and first filtered. The absorbance of filtered solution was measured by using Ultra Violet
spectrophotometric method at 237.5 nm and concentration of the drug was determined from standard calibration curve.
In vitro drug release studies details:
Dissolution test apparatus
0.1 N HCL as Dissolution medium
900 ml Dissolution medium volume
37 ± 0.5°C as std. Temperature
50 rpm Speed of basket paddle
5 min sampling intervals
10 ml volume Sample withdraw
237.5 nm Absorbance measured
4. Result and discussion:
4.1 Pre compression Parameter and studies
Formulation
code
Angle of Repose Bulk density
(weight/ml)
Taped Density
(weight/ml)
Flow rate of
Granules(in min)
Flow Property
of Granules
C1 28.92±0.70 0.54±0.02 0.49±0.04 100 in 16 second Excellent
C4 25.14±0.45 0.54±0.02 0.48±0.02 100 in 16 second Good
C5 24.40±0.69 0.53±0.03 0.48±0.02 100 in 19 second Good
4.2 Post compression Parameter Studies.
Formulation
code
Hardness
(KG/cm2
)
Friability
(%)
Thickness
(mm)
Diameter
(mm)
Weight of
20 tablet
Weight
(mg)
C1 4.10 0.85 4.08 9.02 8.100 gm 405
C2 4.00 0.74 4.12 9.04 7.920 gm 396
C3 4.20 0.70 4.07 9.00 7.980 gm 399
C4 4.30 0.60 4.05 9.02 8.200 gm 410
C5 4.10 0.65 4.10 9.01 8.160 gm 408

4.3 Post compression studies:
Formulation
code
Assay of Drugs
(%)
Water intake time
(seconds)
Disintegration time
(seconds)
Dissolution
(%)
C1 98.66 08-12 12-14 94.85
C2 98.68 12-14 13-15 92.87
C3 98.45 15-17 14-18 88.56
C4 98.56 19-21 19-20 85.87
C5 98.45 20-24 21-23 83.41
5. Graphs.
NIFEDPINE 20 MG TAB. ASSAY GRAPHS NIFEDIPINE 20 MG TAB. DISSO. GRAPHS
NIFEDIPINE DISSO STABILITY DATA
NIFEDIPINE ASSAY STABILITY DATA

6. Conclusion:
After the completion of this experiments the result obtained and we conclude that development of orodispersible Nifedipine 20 mg
Tablet formulation by using super disintegrants i.e. Cross carmillose sodium are given the result of dissolution more than
mentioned in the Pharmacopeia. Some result are mentioned below:
1. Active drug Nifedipine with different excipient are stable viz Starch, Talcum, Mannitol, Lactose, Magnesium stearate,
cross carmillose sodium and direct compressible starch.
2. Fast Disintegrating Nifedipine Tablets were successfully prepared by direct compression method.
3. The flow property of the granules and uniformity of the compressed tablet are better as compare the granules prepared by
weight of dry granulation method or by Slugging method.
4. The angle of repose of prepared granules are less than 30º which show the good quality of granules.
5. The hardness of compressed tablet by direct compression method are found in the rage of 4.0 to 4.5 kg/cm2
.
6. The Thickness of the prepared tablets by all three methods was found between 4.05 mm. to 4.12 mm.
7. The Friability of the compressed tablet are within the range i.e. less than 1%. As the size of tablet are small.
8. The in vitro disintegration studies are found to be in 12-23 seconds. Formulation C1 showed in vitro disintegration time is
12-13 seconds.
On the basis of disintegration time formulation C1 which facilitate the faster disintegration in the mouth. The in-vitro
percentage drug releases from fast dissolving tablets of Nifedipine prepared by direct compression method were found to
be in the range of 98.66 %. Hence, finally it was concluded that the prepared oro dispersible tablets of Nifedipine 20 mg
may prove to be potential candidate for effective fast disintegrating tablet Dosage form.
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