Formulation and Evaluation of Dispersible Tablet of Monteleukast Sodium

 

Aditi Bhatt, Amit Alexander, Akansha Bhandarkar, Pankaj Sahu, Palak Agrawal, Tripti Banjare, Swapnil Gupta, Hemlata Sahu, Shradha Devi Diwedi, Siddharth Kumar Sahu, Pooja Yadav, Kailash Sahu, Deeksha Dewangan, Hemlata Thapa, Deepika, Mukesh Sharma, Vinay Sagar Verma, D. K. Tripathi, Ajazuddin*

 

ABSTRACT:

Monteleukast sodium is most commonly used in treatment of Asthma. It mainly prevents leukotriene mediated effect associated with asthama. Dispersible tablet are film coated or uncoated tablet that can be dispersed in liquid medium before administration, giving a homogenous dispersion. Dispersible tablet were prepared by using a direct compression method employing super disintegrating agentsuch as cross povidone, cross carmellose sodium and sodium starch glycolate, the tablet were preparedusing various diluents like MCC and lactose. Magnesium stearate and talc is used as a lubricant and glidant. Pre-compression parameter such as angle of repose, bulk density, tapped density, carrs index, hausner ratio carried out to study the flow properties of powder to achieve uniformity of tablet. The prepared tablet were evaluated for hardness, thickness, weight variation friablitity, % drug content, disintegration time and other parameter such as wetting time were also evaluated.

 

 

 

INTRODUCTION:

Oral route of drug administration has been used most preferably for both conventional as well as for novel drug delivery because of the ease of administration and wide spread acceptance by patient^1,2. Dispersible tablet are film coated or uncoated tablet that can be dispersed in liquid medium before administration, giving a homogenous dispersion^3,4,5,6. Monteleukast sodium is most commonly used in treatment of asthma. It mainly prevents leukotriene mediated effect associated with asthama^8,9,10,11. Monteleukast sodium is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT1 receptor^{12,13,14,15,16}. Bioavailability of monteleukast sodium is 63%^17,18,19,20. It is usually administered orally²¹.

 

The key properties of dispersible tablet are fast absorption or wetting of water into the tablets and disintegration of associated particles into individual components for fast dissolution^{22,23,24,25,26}. Here in this study the dispersible tablet were prepared by direct compression method^27,28,29. Employing super disintegrating agent such as cross povidone³⁰, cross carmellose sodium^31,32 and sodium starch glycolate^33,34; the tablet were preparedusing various diluents like MCC^34,35 and lactose^36,37. Magnesium stearate^38,29 and talc²¹ is used as a lubricant and glidant.

 

MATERIAL AND METHOD:

Chemicals:

Monteleukastsodium, cross carmellose sodium, cross povidone, sodium starch glycolate, micro crystalline cellulose, lactose, talc, magnesium stearate.

 

 

 

 

 

Equipment:

UV-Visible Spectrophotometer, Tablet Compression machine, Dissolution apparatus, disintegration test apparatus.

 

Preparation of standard calibration curve of monteleukastsodium:

Preparation of dilution media:

Firstly 7.4 pH phosphate buffer was prepared. Prepared buffer was sonicated for few minutes obtaining uniform solution. Further 0.5% sodium lauryl was mixed uniformly.

 

Preparation of standard monteleukast sodium solution:

10 mg of monteleukast sodium was weighed and transferred into 10 ml volumetric flask. Volume is made up to 10 ml using ethanol to obtain a solution that has a concentration equal to 1 mg/mlstandard solution.

 

Procedure for construction calibration curve:

To a series of 10 ml volumetric flask, carefully transferred aliquouts of standard drug solution (0.2, 0.4, 0.6, 0.8, 1.0 ml) and the volume was made up with diluents. The instrument was set for photometric mode and absorbance of each solution was recorded at 287.3 nm against the blank diluents (Figure 1).

 

Preparation of dispersible tablet of monteleukast sodium by direct compression method:

Dispersible tablet of Monteleukast sodium were prepared by direct compression method. Five different formulations were prepared of monteleukast sodium with different composition of polymer and excipient ratio (Table 1).

 

All ingredients were weighed individually and shifted manually through mesh 40 separately. Thereafter all ingredient talc and magnesium stearate were added and mixed for 5 minutes. Dry the blend in oven for few minutes. Finally magnesium stearate and talc was added as lubricant and glidant and mixed for 5 minute. Then tablet was compressed using tablet punching machine.

 

EVALUATION: PRE-COMPRESSION PARAMETER:

All the observations have been tabulated in Table2.

 

Angle of repose:

Friction force of powder can be measured by the angle of repose. It is maximum angle possible between the surface pile of powder and the horizontal plane. It is measured using fixed funnel method. The funnel is kept vertically attacked to a stand at a specific height, below which a paper is kept on a horizontal surface. The funnel is first filled with the powder and then opened to release the same in a form of conical heap; the height of heap is measured with scale. Angle of repose is calculated from this formula:

 

θ = tan^-1 h/r

Where,

h = height of pile (cm)

r = radius of base of pile (cm)

 

Bulk density:

It is define as mass of powder divided by bulk volume. It is calculated using following formula:

 

Bulk density= Weight of sample taken / volume noted a sample

 

Tapped density:

It was determined by placing the powder in a measuring cylinder and tapping it 100times, the total mass of powder was determined and density was calculated using the formula:

 

Tapped density = Vb/Vf

Where,

Vb = initial volume,

Vf = tapped volume

 

Carrs index:

It was calculated using measured values of bulk and tapped density as:

 

Carr’s index = [(Vt-Vb)/Vt] x 100

Where,

Vt = tapped volume

Vb = bulk volume

 

Hausner’s ratio:

It is also calculated from using measured values of bulk and tapped density as:

 

Hausner’s ratio = Dt/Do

Where,

Dt = tapped density,

Do = bulk density

 

POST COMPRESSION PARAMETER:

Weight variation:

20 tablets were selected at a random and average weight is calculated. Then individual tablet were weighed and individual weight was compared with an average weight.

 

Percentage weight variation = (average wt – individual wt)/average weight x 100

 

 

 

Friability:

The friability of ten tablets was determined by using roche friabilator at 25 rpm for 4 minute. % friability of tablet less than 1% are considered.

 

F =Wt –Wo/Wo x 100

 

Where,

F = friability

Wo = initial weight of tablet before test

Wt = tablet weight after test

 

Thickness:

Thicknesses were measured by using vernier calliper and values were tabulated. Three tablet of each batch were measured.

 

Hardness:

The hardness of tablets was determined using Monsanto hardness tester. It is expressed in kg/cm². Hardness indicates the ability of a tablet to withstand mechanical shock while handling. Three tablets were randomly picked and hardness of the same tablet from each formulation was determined.

 

Drug content:

Twenty tablet of each formulation were weighed and powdered. The quantity of powder equivalent to 10 mg of monteleukast sodium was transferred into a 100 ml standard flask and volume made up with 0.5% sodium lauryl sulphate.

 

In vitro disintegration time:

Disintegration time has been measured by using disintegration test apparatus. Placedone tablet in each of the 6 tube of basket and run the apparatus using PH 6.8 (simulated salivafluid) maintained at 37°±1°C as the immersion liquid. The assembly should be raised and lowered between 100 cycles per minute .the time in second taken for complete disintegration of the tablet with no palpable mass remaining in the apparatus was measured recorded.

 

Water absorption ratio:

A piece of tissue paper folded twice was placed in a small petri dish containing 6 ml of water. A tablet was put on the paper and time required for complete wetting was measured. The wetted tablet was then weighed. Water absorption ratio R, determined using following formula

 

R Wa-Wb/Wb x 100

 

Invitro dissolution study:

The dissolution rate of monteleukast sodium from the dispersible tablet was studied in 900 ml of water containing 0.5% sodium lauryl sulphate using dissolution test apparatus with paddle stirrer at 50 rpm. A temperature of 37⁰C±0.5⁰C was maintained throughout the study. Sample of dissolution media were withdrawn at time interval 2, 5, 10, 20, 30, 40, 50, 60 minute and assayed for monteleukast sodium. The sample of dissolution fluid withdrawn at each time was replaced with fresh dissolution fluid.

 

Spectral analysis of the best formulation:

A drug-polymer compatibility was analyzed using Fourier Transform Infrared spectrophotometer (Varian 640-IR, USA).The spectra were taken in the wave number region 4000-400 cm⁻¹ as KBr pellets of drug (Monteleukast Sodium), polymer, physical mixture of drug and polymer and tablet.

 

RESULT:

 

Fig. 1: Standard calibration curve for pure drug monteleukast sodium.

 

Table 1: Details about the ingredients employed in various amount in formulating different formulations.

Ingredient(mg)	F1	F2	F3	F4	F5	F6
Monteleukast sodium	10.0	10.0	10.0	10.0	10.0	10.0
Crosscarmellose sodium	-	-	16.0	9.0	-	-
Cross povidone	8.0	-	-	-	5.5	-
Sodium starch glycolate	-	6.5	-	-	-	14.5
Microcrystalline cellulose	-	80.0	-	76.0	79.0	-
Lactose	77.0	-	68.0	-	-	70.0
Magnesium stearate	2.0	1.0	2.5	2.5	2.5	1.5
Talc	2.0	1.5	2.5	1.5	2.0	3.0
Orange flavour	1.0	1.0	1.0	1.0	1.0	1.0
Total weight (mg)	100	100	100	100	100	100

Table 2:    Pre-compression parameters of the various formulated tablets.

Formulation	Bulk density	Tapped density	Carrs index	Angle of repose	Hausners ratio
F1	7.5	6.2	19.1	28.4	1.15
F2	8.0	6.5	18.6	28.4	1.16
F3	7.6	6.3	18.5	29.9	1.14
F4	8.7	7.0	21.1	29.5	1.19
F5	7.4	6.1	20.3	31.3	1.14
F6	7.0	5.7	18.9	28.7	1.13

 

Table 3: Post-compression parameters of the various formulated tablets.

Formulation	Weight variation (mg)	Thickness (nm)	Hardness (kg/cm3)	Friability (%)
F1	96.7	2.3	3.5	0.39
F2	96.8	2.5	3.9	0.27
F3	99.06	2.6	3.2	0.34
F4	98.4	2.7	4.2	0.45
F5	97.3	2.22	3.6	0.40
F6	94.8	2.8	4.1	0.31

 

Table 4: Observation table for dissolution parameters of compressed tablets, of various formulations.

Formulation	Weight variation (mg)	Thickness (nm)	Hardness (kg/cm3)	Friability (%)
F1	96.7	2.3	3.5	0.39
F2	96.8	2.5	3.9	0.27
F3	99.06	2.6	3.2	0.34
F4	98.4	2.7	4.2	0.45
F5	97.3	2.22	3.6	0.40
F6	94.8	2.8	4.1	0.31

 

Table 5: Observation table for various physical tests of compressed tablets, of various formulations.

Formulation	Drug content (%)	Wetting time	Water absorption ratio	disintegration time(second)
F1	96.7	26.7	206.7	47
F2	94.3	30.7	203.9	34
F3	90.7	25.9	205.9	30
F4	97.5	27.6	208.7	22
F5	96.8	24.8	207.9	32
F6	93.6	28.8	205.5	28

 

Table 6: Observations of the dissolution studies performed of all the compressed tablets of various formulations 900 ml water at 37°C±0.5°C.

Formulation	Time(seconds)
	2	5	10	20	30	40	50	60
FI	8.07	16.80	22.49	34.54	46.97	54.51	61.3	71.36
F2	10.21	19.59	26.21	39.06	49.87	59.98	68.64	79.43
F3	13.65	22.08	34.98	44.91	53.76	69.08	82.98	89.78
F4	18.09	26.64	34.92	46.67	59.78	75.87	90.12	98.79
F5	11.37	21.87	29.87	43.01	51.67	67.07	78.56	82.49
F6	14.38	25.97	33.76	45.32	57.83	75.93	88.98	96.76

 

 

Fig 2: Dissolution profile of various formulations’ compressed tablets of different formulations.

 

 

Fig 3: IR spectra of pure drug and the formulation showing best results, so as to confirm there is no drug-excipient interaction.

 

DISCUSSION:

Dispersible tablet of monteleukast sodium tablets were formulated by direct compression method using cross carmellose sodium, cross povidone, sodium starch glycolate, microcrystalline cellulose, lactose magnesium stearate for developing controlled release dosage form. Different parameter pre-compression and post-compression studies are carried out. After that the formulation F4 was found to be best on the basis of In-vitro disintegration time and In-vitro dissolution time. The value of pre compression parameters evaluated within a prescribed limit and indicates good free flowing property. Post compression studies like hardness, friability, weight variation, in vitro wetting time, In-vitro disintegration and In-vitro dissolution time. All parameters evaluated are within the limits. The hardness was found to be in the range of 3 to 5kg/cm²for all formulations indicating good mechanical strength with an ability to withstand physical and mechanical stress condition while handling. In all formulations the friability value are less than 1% and meet the IP limit. All tablets of batch pass the percent weight variation test. The percentage drug content of all the tablets was found to be above 93%; which was within the acceptable limits. Wetting time and disintegration time were found to be in prescribed limits. It was observed that when cross carmellose sodium was used as disintegrant, the tablet disintegrates rapidly within less time due to easy swelling ability of cross carmellose sodium when compared to other tablet prepared by using cross povidone and sodium starch glycolate. Among the formulation of tablet formulation F4 containing cross carmellose sodium was found to be the best when compared to other formulation. The FTIR spectra confirmed that there is no interaction of montelukast sodium with its excipients.

 

CONCLUSION:

Monteleukast sodium dispersible tablets were prepared by using different super disintegrating agent cross carmellose sodium, cross povidone, sodium starch glycolate. The formulation F4 was found to be best based on different pre-compression and post compression study. In formulation, F4 cross carmellose sodium is used as a super disintegrating agent.

 

ACKNOWLEDGMENT:

Authors want to acknowledge the facilities provided by the Rungta College of Pharmaceutical Sciences and Research, Kohka, Kurud Road, Bhilai, Chhattisgarh, India. The authors also wants to acknowledge Chhattisgarh Council of Science and Technology (CGCOST) for providing financial assistance under mini research project (MRP) vide letter no. 1124/CCOST/MRP/2015; Dated: September 4, 2015 and 1115/CCOST/MRP/2015; Dated: September 4, 2015.

 

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Accepted on 25.01.2018          © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(4): 1627-1632.