Formulation and Characterization of fast Dissolving tablets of Perindopril

 

Raut Indrayani D*,  Gharge  Manisha, Dandwde Sonli, Mohite S.K., Magdum C.S.

Rajarambapu College of Pharmacy, Kasegaon MS( India)

*Corresponding Author E-mail: indrayaniraut7363@rediffmail.com

 

ABSTRACT:

In this investigation fast dissolving tablets of perindopril were prepared using different superdisintegrants like sodium starch glycolate and crosspovidone by direct compression method. Fast dissolving drug delivery is fastest, safest, convenient and most economic method of drug delivery having the highest patient compliance and preferred over conventional tablets therefore it is currently the gold standard in the pharmaceutical industry. Formulations were evaluated for precompressional parameters bulk density, tapped density, cars index, angle of repose etc and postcompressional parameters like uniformity of weight, thickness, hardness, friability, drug content, wetting time, water absorption ratio, in vitro disintegration time and in vitro dissolution study. The formulation A1 to A3 contain increasing concentration of Sodium starch glycolate showed the increases dissolution rate of drug release  from 92.75 to  98.25  in 15 min, whereas formulation B1 to B3 contain crosspovidone in increasing concentration also increases the drug release from 94.75 to 99.02 in 15 min. The drug release from FDTs increased with increasing concentration of superdisintegrants and was found to be highest with formulations containing Crosspovidone as compared to sodium starch glycolate.

 

KEY WORDS: Fast dissolving, Perindopril, Superdisintegrants, drug release etc.

 

 


INTRODUCTION:

A fast dissolving system can be defined as a dosage form for oral administration, which when placed in mouth, rapidly dispersed or dissolved and can be swallowed in form of liquid. Fast dissolving tablets (FDTs) are solid single-unit dosage forms that are placed in mouth, allowed to disperse/dissolve in the saliva without the need of water and provides a quick onset of action. Some drugs are absorbed from mouth, pharynx and oesophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form.1

 

Recently fast dissolving formulation is popular as NDDS because they are easy to administer and lead to better patient compliance. Pediatric and geriatric patient have difficulty in swallowing the conventional dosage forms. Fast dissolving and fast dispersing drug delivery system may offer a solution to these problems. FDTs are prepared by various techniques, mainly direct compression, Lyophilization and moulding. The simplicity and cost effectiveness of the direct compression process have positioned this technique as an attractive alternate to traditional granulation technologies4. Usually superdisintegrants are added in the drug formulation to facilitate the break-up or disintegration of tablet into smaller particles that can easily dissolve more rapidly than in absence of disintegrants. Perindopril ter-butyl amine belongs to a group called Angiotensin Converting Enzyme (ACE) inhibitors. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma rennin activity and decreased aldosterone secretion. The overall effect of this is a drop in blood pressure and a decrease in the workload of the heart. Perindopril is a pro-drug that is hydrolyzed by esterases to the active metabolite perindoprilat. Perindopril is rapidly absorbed, reaching peak plasma concentration about 1 hour after a single oral dose. Perindopril at reaches peak plasma concentrations in 2 to 6 hours. The bioavailability of Perindopril is about 70%. Here we used superdisintegrants like sodium starch glycolate and crosspovidone and the comparison of these two superdisintegrants also  studied.2

 

MATERIAL AND METHOD:

Perindopril obtained as a gift sample from Lupin Ltd Research path, pune. Crosspovidone, Sodium starch  glycolate, Mannitol, Talc, Magnesium stearate, from Research lab Fine chemical industries Islampur. All the ingredients were of pharmacopeial grade and used as supplied.

 

Preparation of Fast Dissolving Tablets:

The critical parameters to formulate a fast dissolving tablet are choice of superdisintegrants and optimization of concentration of superdisintegrant. The super disintegrant (Crospovidone, Sodium Starch Glycolate) were used to formulate the tablets. All the ingredients as shown in Table 1 were co-ground in a pestle and motor and then talc and magnesium stearate were added and mixed for 10 minutes. The mixed blend of drug-excipient was compressed using 8 station compression machine.2, 3


 

Table 1: Formulation Table

Ingredients

A1

A2

A3

B1

B2

B3

Perindopril

4

4

4

4

4

4

Mannitol

137

134.5

132

137

137.5

132

Sodium Starch Glycolate

5

7.5

10

-

-

-

Crosspovidone

-

-

-

5

7.5

10

MCC

50

50

50

50

50

50

Talc

2

2

2

2

2

2

Magnesium stearate

2

2

2

2

2

2

Total

200

200

200

200

200

200

 

 

 


Characterization:

I)    Pre compression Parameters4,5:

1. Bulk Density (Db):

It is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring the weight powder (passed through standard sieve # 20) into a measuring cylinder and initial weight was noted. This initial volume is called the bulk volume. From this the bulk density is calculated according to the formula mentioned below. It is expressed in g/ml and is given by

 

Db = M/ Vb

Where, M is the mass of powder

Vb is the bulk volume of the powder.

 

2. Tapped Density (Dt):

It is the ratio of total mass of the powder to the tapped volume of the powder. Volume was measured by tapping the powder for 750 times and the tapped volume was noted if the difference between these two volumes is less than 2%. If it is more than 2%, tapping is continued for 1250 times and tapped volume was noted. Tapping was continued until the difference between successive volumes is less than 2 % (in a bulk density apparatus). It is expressed in g/ml and is given by

 

Dt = M / Vt

Where, M is the mass of powder

Vt is the tapped volume of the powder.

3. Angle of Repose (θ):

The friction forces in a loose powder can be measured by the angle of repose (q). It is an indicative of the flow properties of the powder. It is defined as maximum angle possible between the surface of the pile of powder and the horizontal plane.

 

tan (θ ) = h / r

θ = tan-1 (h / r)

Where, q is the angle of repose.

h is the height in cms

r is the radius in cms.

 

The powder mixture was allowed to flow through the funnel fixed to a stand at definite height (h). The angle of repose was then calculated by measuring the height and radius of the heap of powder formed. Care was taken to see that the powder particals slip and roll over each other through the sides of the funnel. Relationship between angle of repose and powder flow property.

 

4. Carr’s index (or) % compressibility:

 It indicates powder flow properties. It is expressed in percentage and is give

 

        Dt – D

I = ------------ x 100

          D

Where, Dt is the tapped density of the powder and  Db is the bulk density of the powder.

 

5. Hausner ratio:

Hausner ratio is an indirect index of ease of powder flow. It is calculated by the following

formula.

                             Dt

Hausner ratio = -------

                             Db

Where, Dt is the tapped density.

Db is the bulk density.

 

Lower hausner ratio (<1.25) indicates better flow properties than higher ones (>1.25)

 

ii)   In Vitro Evaluation Tests5, 6

1.    Uniformity of weight:

Twenty tablets were taken and their weight was determined individually and collectively on a digital weighing balance. The average weight of one tablet was determined from the collective weight.

 

2.    Hardness:

Hardness or tablet crushing strength (fc ), the force required to break a tablet in a diametric compression was measured using Monsanto tablet hardness tester. It is expressed in kg/cm2.

 

3.    Tablet thickness:

Tablet thickness can be measured using Varnier calipers. The thickness was measured by placing tablet between two arms of the Varnier calipers.

 

4.    Friability:

The friability of sample of six tablets ware measured using a Roche Fribilator. Six pre-weighed tablets were rotated at 25 rpm for 4 minutes. The tablets were then reweighed after removal of fine’s using 60 mesh screens and the percentage of weight loss was calculated.

 

% Friability = (Loss in weight / Initial weight) × 100

 

5.    Drug Content:

The test is mandatory for tablets with 10mg or less weight of active ingredient Ten randomly selected tablets from each formulation were finely powdered and powder equivalent to 4 mg of Perindopril was accurately weighed and transferred to 100 ml volumetric flasks containing 50 ml of 0.1N HCL. The flasks were shaken to mix the contents thoroughly. The volume was made up to the mark with 0.1 N HCL and filtered. One ml of the filtrate was suitably diluted and Perindopril content was estimated at 215.0 nm using a double beam UV visible spectrophotometer.

 

6.    Wetting time and water absorption ratio7:

A piece of paper folded twice was kept in a Petri dish (internal diameter 5.5 cm)containing 6 ml of purified water. A tablet having a small amount of Rosaline dye powder on the upper surface was placed on the tissue paper. The time required to develop a red colour on the upper surface of the tablet was recorded as the wetting time. The same procedure without Rosaline dye powder was followed for determining the water absorption ratio R was determined according to the following equation:

R = [(Wa – Wb)/Wb ]× 100

where, Wb and Wa were the weights of  the tablet before and after use.

 

7.    Disintegration time :

The test was carried out using Tablet disintegration tester in distilled water at 37ºC ± 2ºC was used as a disintegration media and the time in second taken for complete disintegration of the tablet with no palable mass remaining in the apparatus was measured in seconds.

 

8.    In Vitro Dissolution :

The release rate perindopril   from fast dissolving tablets was determined using United State Pharmacopoeia (USP) XXIV dissolution testing apparatus II (paddle method). The dissolution test was performed using 900 ml of 0.1 N HCl (PH=1.2), at 37± 0.50C and 50 rpm. A sample (10 ml) of the solution was withdrawn from the dissolution apparatus at 1, 2, 5, 10, 15, 20, 25 and 30min. The samples were replaced with fresh dissolution medium of same quantity. The samples were filtered through 0.45 μ membrane filter. Absorbance of these solutions was measured at 215 nm using a Shimadzu UV-1800 UV/Vis double beam spectrophotometer. Cumulative percentage of drug release was calculated using an equation obtained from a calibration curve.

 

RESULT AND DISCUSSION:

The present study was undertaken to formulate and evaluate fast dissolving tablet of Perindopril by direct compression method using different concentrations of crosspovidone (5% - 10%) and sodium starch glycolate (5% - 10 %) as superdisintegrants. Pre compression parameters were studied like angle of repose and the compressibility values varied from 25.44 to 29.74 respectively. Bulk densities of various formulations varied 0.31to 0.42 gm/cc. From these values, it was evident that these blends had good flow properties. Post compression parameters were studied like  Hardness, thickness and friability of all the tablet formulations were observed in the range of 3.0 ±0.14 to 4±0.22 kg/cm2, 1.55± 0.14to 1.92 ± 0.25 mm and 0.51 to 0.86%, respectively. Weight variation was found within the specification of the Within the IP Limits of ±7.5%. Average weight of 20 tablets of all ten formulations was found in the range of 199.5±7.3-201±7.1. The in-vitro disintegration time was studied by the time taken to undergo complete disintegration and was observed rapid with the batches containing Sodium starch glycolate (9.08±0.58 to 14.00±0.86 sec) and Crosspovidone (12.00±0.16 to 22.00±0.44 sec) and. The rapid disintegration may be due to the rapid uptake of water from the medium, swelling and bursting effect.  Wetting time and water absorption ratio was found in the range of 9.08±0.58 to 22.00±0.44 sec and 36.82±0.36 to 44.34±0.16 %, respectively, which facilitate the faster dispersion in the mouth. Drug content of all the formulations was found in the range of 96.24±0.16 to 96.32±0.46 %. In vitro dissolution studies of various formulations at different time intervals are reported.

The formulation A1 to A3 contain increasing concentration of Sodium starch glycolate showed the increases dissolution rate of drug release  from 92.75 to 98.25 in 15 min, whereas formulation B1 to B3 contain crosspovidone in increasing concentration also increases the drug release from 94.75 to 99.02 in 15 min. From the overall observations, increasing concentration of crosspovidone increases the drug release also as compared to sodium starch glycolate.

 

Figure.1: Calibration curve


 

Table 2: Pre Compression evaluation parameters

Sr

No.

Formulation code

Angle of Repose(θ)

Bulk Density (gm/cc)

Tapped Density (gm/cc)

Carr’s Index

(%)

Hausner’s

Ratio

Flow Rate

Gm/sec

1

A1

28.86

0.42

0.49

14.25

1.16

48

2

A2

25.51

0.31

0.41

24.94

1.33

51

3

A3

26.69

0.34

0.51

33.39

1.50

53

4

B1

25.44

0.35

0.45

22.24

1.28

46

5

B2

27.55

0.31

0.42

25

1.33

50

6

B3

29.77

0.36

0.54

33.33

1.50

52

 

Table 3: In Vitro evaluation parameters

Parameters

Formulation Code

A1

A2

A3

B1

B2

B3

Hardness±SD (kg/cm)

3.00± 0.14

3.01± 0.22

5.0± 0.20

3.3± 0.30

3.3± 0.18

4.0± 0.22

Thickness±SD (mm)

1.55± 0.14

1.67± 0.40

1.80± 0.18

1.87± 0.16

1.82± 0.15

1.92± 0.25

Friability  (%)

0.62

0.86

0.56

0.72

0.58

0.82

In-vitro disintegration time±SD(sec)

122±0.52

134±0.22

150±0.18

52±0.28

55±0.62

57±0.84

Wetting Time±SD(sec)

14.00±0.86

11.33±0.62

9.08±0.58

22.00±0.44

18.46±0.65

12.00±0.16

Water Absorption ratio±SD(%)

44.34±0.16

38.56±0.86

40.62±0.72

36.82±0.36

40.24±0.48

42.64±0.62

Percent Drug Content±SD

98.72±0.22

96.62±0.16

99.02±0.12

96.32±0.46

98.24±0.16

99.32±0.14

In vitro Drug release %

92.75

94.05

98.25

94.75

96.25

99.02

Weight Variation(%)

(199.5±7.3-201±7.1) Within the IP Limits of ±7.5%

 

Figure 2: In vitro drug release

CONCLUSION:

The rapid disintegrating tablets have potential advantages as compared to conventional dosage forms. Because of increased patient demand. Good bioavailability and  rapid onset of action, these are expected to become more popular in today’s leading World. Choice of drug Perindopril was associated with its ACE property. The powder was characterized on the basis of micromeritic Properties (Angle of Repose, Bulk Density, Tapped Density, Compressibility Index, Hauser’s Ratio).and prepared tablet were evaluated as Weight variation, thickness, hardness, in vitro disintegration and dissolution study. In the present investigational study, it was concluded that as the concentration of superdisintegrants increases the % drug release also increases and bioavailability also increases. The Comparison study of sodium starch glycolate and Cross povidone superdisintegrants were studied and concluded that crosspovidone show more % drug release as compared to sodium starch glycolate at same concentration.

 

ACKNOWLEDGEMENTS:

Authors are thankful to Lupin Ltd Research path, Pune, for providing gift samples of Peridopril. Authors are also thankful to the principal Rajarambapu college of Pharmacy, Kasegaon for providing lab facilities to carry out the research work.

 

REFERENCES:

1.     Lachman L, Liberman H, Kanig J. The Theory and Practice of Industrial Pharmacy. 3rd ed. Bombay: Varghese Publishing House 1989: 293-345.

2.     Ratnaparkhi Mukesh P., Jagadale Sachin K., Patil Pradeep S. and Dhiwar Suresh B “Formulation Development and Evaluation of taste masked orally disintegrating tablets of Perindopril Erbumine by direct Compression method” Int. J. Drug Dev.  and  Res., July-September 2012, 4(3): 374- 394

3.     Rohan Patil, Neha Patil, Aniket Patil, S. J. Shid, V.N. Dange, C.S. Magdum, S.K. Mohite. Preparation and Evaluation of Fast Dissolving Tablet Tramadol Hydrochloride. Asian J. Pharm. Tech. 2016; 6 (3): 183-185.

4.     Liberman H, Lachman L. The Theory and Practice of Industrial Pharmacy. 3rd ed. Bombay: Verghese Publication House; 1991. p. 171-93.

5.      Indian Pharmacopoeia. 4th ed, Vol. II: Controller of Publications, Govt. of India, Ministry of Health  and Family Welfare, New Delhi; 1996: p. 735.

6.     Raut Indrayani D, Mane Pallavi, Mane Dipak, Mohite S.K, Magdum C.S.  Design and characterization of fast dissolving tablets of valsartan using synthetic and natural superdisintegrants International Journal of Advanced Research (2015), Volume 3, Issue 3, 1207-1212.

7.     C.P. Jain and P.s. Naruka, Formulation and evaluation of fast dissolving tablets of Valsartan, International journal of pharmacy and pharmaceutical science, vol. 1,issue 1, july-sept 2009.

 

 

 

 

Received on 19.11.2016       Accepted on 11.01.2017     

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2017; 7(1): 51-55.

DOI: 10.5958/2231-5713.2017.00008.3