MIT International Journal of Pharmaceutical Sciences, Vol. 3, No. 1, January 2017, pp.

21–24 21
ISSN 2394-5338 (Print); 2394-5346 (Online) © MIT Publications

Original Article

Formulation and in-vitro dissolution of Clopidogrel tablet by using sodium starch glycolate
and natural xanthan gum
Prasanta K. Mohapatra *, Hitesh Kumar, Ashok Kumar, Vaibhav Rathore
Moradabad Educational Trust, Group of Institutions, Faculty of Pharmacy, Moradabad, Uttar Pradesh, India
*Corresponding Author. Tel: +91 9000261204; E-mail address: [email protected]

ARTICLE INFO ABSTRACT

Received 3 Jan 2017 Different formulations were made with an aim to develop stable, cost effective
Revised 5 Feb 2017 Clopidogrel tablets by direct compression technique. Four formulations (F1 – F4)
Accepted 10 Feb 2017 having Primojel and xanthan gum at different concentrations level were prepared.
The prepared batches of tablets were evaluated for hardness, friability, disintegra-
Keywords: tion and in-vitro dissolution study. All The formulations containing combination of
• Anti-platelet agent Primojel and Xanthan gum showed different in-vitro disintegration time and drug
• Clopidogrel bisulphate release.
• Direct compression technique

1. INTRODUCTION 2. EXPERIMENTAL
The goal of any drug delivery system is to provide a therapeutic 2.1 Chemicals
amount of drug in the proper site in the body to achieve promptly Clopidogrel bisulphate, Xanthan gum, Corn Starch, Primojel,
and then to maintain the desired drug concentration [1-3]. That is, Talc, Ethyl cellulose, Lactose were obtained from the college.
All the materials were of pharmacopoeia grade.
the drug delivery system should deliver drug at a rate dedicated by
the needs of the body over a specified period of treatment. Tablet 2.2 Procedure
is the most widely used dosage form because of its convenience in Tablets were prepared by direct compression method and various
terms of self-administration, compactness and ease in manufacturing formula used in the formulation are shown in table. Each
[4]. They can be mass produced with robust quality controls formulation having different ratios of following ingredients are
and other different branding possibilities by means of colored mixed uniformly.
film coating different sizes and shapes for better appearance Table 1: Formulation of film coated Clopidogrel tablets
and improving the patient compliance [5-8]. Clopidogrel is an Ingredients Formula- Formula- Formula- Formula-
(mg) tion (F1) tion (F2) tion (F3) tion (F4)
inhibitor of platelet aggregation used in the management and
Clopidogrel 75 75 75 75
prevention of thromboembolic disorders. It is used as adenosine
Xanthan gum 25 50 75 92
diphosphate receptor antagonists in an anti platelet therapy. It is
Corn Starch 60 60 60 60
efficacy in reducing the stroke is similar or more to that of aspirin.
Primojel 67 42 17 00
Pharmaceutical excipients can be defined as any substance other
Talk 4 4 4 4
than the active and is included in the formulation for improving
Ethyl cellulose 64 64 64 64
the pharmacokinetic parameters. Corn Starch, Primojel, are some
Lactose 40 40 40 40
of the super-disintegrants included in the immediate release tablets
335 mg 335 mg 335 mg 335 mg
for better onset of action [9-14].
 MIT International Journal of Pharmaceutical Sciences, Vol. 3, No. 1, January 2017, pp. 21–24 22
ISSN 2394-5338 (Print); 2394-5346 (Online) © MIT Publications

2.3 Preparation of coating solution Table 3: Calibration curve of Clopidogrel

3000 mg of accurately weighed corn-starch was added in 100
Concentration (µg/ml) Absorbance
mL of distilled water to obtained 3 % w/v of solution and stirring
was carried out using a propeller stirrer (Remi, Mumbai, India) 2 0.091
at 1000 rpm for 45 min. 4 0.198
6 0.315
2.4 Coating of tablets
8 0.412
The tablets were film-coated using a side-vented, perforated pan
coating machine (Neo Machine Mfg. Co. Pvt. Ltd. Calcutta, 10 0.528
India). Inlet air spray-rate and exhaust air spray-rate were kept
constant at 150 f3 / m and 200 f3 / m, respectively. First fixed
quantity (2 kg) tablets were kept in the pan which was pre-
adjusted at 50° C temperature for 10 min. Then actual weight
of tablet was determined. Then, various parameters like spray
rate, inlet air temperature and rotating speed of pan were adjusted
and studied with different levels. After finishing of the coating
tablets were kept in the pan at 60° C and 2 rpm for curing. Then
tablets were removed from the pan and evaluated.
Table 2: Coating formula for film coated Clopidogrel tablets
Sl. Qty./1000
Ingredients Uses
No. Tablet (gm)
Film forming
1. Hypromellose 6.60
agent
2. Lactose monohydrate Filler 0.69
Fig. 1. Calibration curve of Clopidogrel
3. Titanium dioxide Opacifier 3.72
4. Triacetin Plasticizer 1.38 2.7 In-vitro drug release study
5. Iron oxide red Color 0.03
The in-vitro release of Clopidogrel film coated tablet was
6. Purified water Vehicle 95.00 monitored in phosphate buffer, pH 7.2 at 37º C ± 1º C using
USP basket type dissolution rate test apparatus. The tablet of
2.5 Characterization of drug different formulations (wt. equivalent to 75 mg pure drug) was
Identification of drug: The drug was identified by, Ultraviolet stirred in 900 ml dissolution medium at 75 rpm. Samples (10 ml)
spectroscopy (UV) and melting point. were withdrawn at predetermined time interval and replenished
(I) Ultraviolet Spectroscopy: A stock solution of Clopidogrel immediately with the same volume of fresh medium. Aliquot’s
(100 mcg/ml) in phosphate buffer of pH 7.2 was prepared. And following suitable dilution, were analyzed spectrophotometrically
scanned spectrophotometrically between 200-400 nm. at 219 nm. The concentrations of Clopidogrel in test samples
were corrected for sampling effect. The drug release experiments
(II) Melting point: The melting point of Clopidogrel sample was were conducted in triplicates. Following the above manner, the
determined by melting point apparatus and found to be 158 °C. dissolution of pure drug was also carried out [15-16].
(III) Preparation of buffer solution of pH 7.2: Weight
separately both Potassium dihydrogen orthophosphate (KH2PO4)
& Sodium Hydroxide (NaOH) to their respective amount (given
below) for 1l tr distilled water and mixed them thoroughly.
KH2PO4 - 6.805 gm
NaOH - 1.388 gm

2.6 Preparation of calibration curve

A stock solution of Clopidogrel (100mcg/ml) in phosphate
buffer of pH 7.2 was prepared. A series of dilutions containing
2, 4, 6, 8, and 10 mg/ml of Clopidogrel were prepared and the
absorbance was measured at 219 nm spectrophotometrically.
A linear regression was drawn by plotting absorbance against
concentration (Figure No. 1), the regression coefficient was also
determined. Fig. 2. In- vitro Dissolution Study of Clopidogrel F1
 MIT International Journal of Pharmaceutical Sciences, Vol. 3, No. 1, January 2017, pp. 21–24 23
ISSN 2394-5338 (Print); 2394-5346 (Online) © MIT Publications

3. RESULTS AND DISCUSSION
All four batches were prepared under same conditions and on
same instruments to minimize variations. Super disintegrants are
generally used by formulation scientist for developing FDTs or
for improvement of solubility of drugs. The primary requirements
of all four formulations are quicker disintegration time. The
dissolution rate of Clopidogrel FDTs of different batches are
shown [figure 6]. The weight variation of 155 mg tablets was
found maximum up to ± 1.2 % RSD. Hardness was found to be
within 3.5 to 4.0 kg/cm2 which limit friability within 0.4 % only.
The drug Contents was found to be within limits and all tablets
Fig. 3. In -vitro dissolution study of Clopidogrel F2 were passing the dispersion test.

4. CONCLUSION
The evaluation results of all four batches were found to be
satisfactory within limit and the disintegration time of Primojel
was quite good with presence of xanthan gum. This clearly
indicates that Primojel has good disintegrating property on
addition of sodium starch glycolate with xanthan gum. In present
study super disintegrant like sodium starch glycolate shows
less disintegration time and as the concentration of xanthan
gum increases dissolution time also increases. Hence it proofs
success of natural xanthan gum in orally disintegrating tablets
formulation at very low concentration and cost.
Fig. 4. In vitro Dissolution Study of Clopidogrel F3
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