INTRODUCTION:

Oral delivery is currently the gold standard in the pharmaceutical industry because of its convenience in terms of self-administration, compactness, economical and ease in manufacturing having the highest patient compliance¹. However, geriatric, paediatric and mentally ill patient’s experiences difficulty in swallowing conventional tablets, which leads to poor patient’s compliance².

To overcome these problems, scientists have developed innovative drug delivery system known as fast dissolving/disintegrating tablets (FDTs)³.

These are novel types of tablets that dissolve/ disintegrate/ disperse in saliva within few seconds without water. According to European pharmacopoeia, these MDTs should dissolve/ disintegrate in less than three minutes. The formulation is more useful for the bed ridden and patients who have the swallowing problem. The benefits of MDTs is to improve patients compliance, rapid onset of action, increased bioavailability and good stability which make these tablets popular as a dosage form of choice in the current market^4-5.

Mouth dissolving tablets are also called as orodispersible tablets, fast disintegrating tablets, orally disintegrating tablets, quick disintegrating tablets, fast dissolving tablets, rapid dissolving tablets, porous tablets, quick melt tablets and rapid melt tablets. When such tablets are placed in oral cavity, saliva quickly penetrates into the pores to cause rapid tablet disintegration.

United States Food and Drug Administration (US FDA) defined fast dissolving tablet (FDT) as “A solid dosage form containing medicinal substance or active ingredient which disintegrate rapidly usually within a matter of seconds when placed up on the tounge”⁶.

Montelukast sodium is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT1 receptor.

Montelukast sodium is an anti-asthmatic, mainly prevents leukotriene mediated effect associated with asthma. Montelukast sodium is a hygroscopic, optically active, and white to off-white powder. Montelukast sodium is freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile.

In the present study an attempt had been made to prepare mouth dissolving tablets of montelukast sodium in the oral cavity with enhanced dissolution rate and hence improved patient compliance. The basic approach used in the development of mouth dissolving tablets is the use of superdisintegrants like croscarmellose sodium crosspovidone and sodium starch glycolate which provide instantaneous disintegration of tablet after putting on tongue, thereby releasing the drug in saliva. These systems may offer superior profile with potential mucosal absorption, thus increase the drug bioavailability.

MATERIAL AND METHODS:

Materials:

Montelukast sodium was obtained as a gift sample from Matrix India (P) Ltd, Hyderabad. Microcrystalline cellulose, Croscarmellose sodium (Ac-di-sol), Sodium starch glycolate and Crospovidone were obtained as a gift samples from Zydus research centre, Ahmedabad. All other chemicals and solvents used were of analytical reagent grade.

Methods:

Drug- polymer interaction studies:

Fourier Transform Infra-Red (FT-IR) spectral analysis:

Fourier–Transform Infrared (FT–IR) spectrums of pure Montelukast sodium and combination of drug and excipients were obtained by a Fourier-Transform Infrared spectrophotometer, (FTIR-8300, Shimadzu, Japan) using the KBr disk method. The scanning range was 400 to 4000 cm^-1 and the resolution was 1cm^-1. This spectral analysis was employed to check the compatibility of drugs with the excipients used.

Preparation of Montelukast sodium by direct compression method:

Mouth dissolving tablets of montelukast sodium were prepared by direct compression method using croscarmellose sodium, crospovidone and sodium starch glycolate as superdisintegrants and manitol and lactose as diluents. The composition of formulation is shown in the table 1 and table 2. The drug, diluents, superdisintegrants and sweetener were screened through 40 mesh and properly mixed together. Talc and magnesium stearate were screened through 80 mesh and blended with initial mixture. Powder thus obtained was compressed into tablets on a 10 station single punch rotary tablet compression machine (Rimek). A biconvex punch 8 mm in diameter was used for tableting. Compression force of the machine was adjusted to obtain the hardness of 3-4 kg/cm².

Table1: Composition of mouth dissolving tablets of Montelukast sodium with microcrystalline cellulose as diluent

INGREDIENTS	FORMULATIONS (mg)
INGREDIENTS	M1	M2	M3	M4	M5	M6	M7	M8	M9	M10	M11	M12
montelukast sodium	10	10	10	10	10	10	10	10	10	10	10	10
Sodium starch glycollate	3	6	9	12	-	-	-	-	-	-	-	-
Croscarmellose sod	-	-	-	-	3	6	9	12	-	-	-	-
Crospovidone	-	-	-	-	-	-	-	-	3	6	9	12
MCC	125.5	122.5	119.5	116.5	125.5	122.5	119.5	116.5	125.5	122.5	119.5	116.5
Aspartame	4	4	4	4	4	4	4	4	4	4	4	4
Cherry flavor	3	3	3	3	3	3	3	3	3	3	3	3
Talc	3	3	3	3	3	3	3	3	3	3	3	3
Magnesium stearate	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5
Total weight	150	150	150	150	150	150	150	150	150	150	150	150

Table 2: Composition of mouth dissolving tablets of Montelukast sodium with Lactose as diluent

INGREDIENTS	FORMULATIONS (mg)
INGREDIENTS	L1	L 2	L 3	L 4	L 5	L 6	L 7	L 8	L 9	L 10	L 11	L 12
montelukast sodium	10	10	10	10	10	10	10	10	10	10	10	10
Sodium starch glycollate	3	6	9	12	-	-	-	-	-	-	-	-
Croscarmellose sod	-	-	-	-	3	6	9	12	-	-	-	-
Crospovidone	-	-	-	-	-	-	-	-	3	6	9	12
Lactose	125.5	122.5	119.5	116.5	125.5	122.5	119.5	116.5	125.5	122.5	119.5	116.5
Aspartame	4	4	4	4	4	4	4	4	4	4	4	4
Cherry flavor	3	3	3	3	3	3	3	3	3	3	3	3
Talc	3	3	3	3	3	3	3	3	3	3	3	3
Magnesium stearate	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5	1.5
Total weight	150	150	150	150	150	150	150	150	150	150	150	150

Evaluation of Mouth dissolving tablets:

PRE-COMPRESSIONAL STUDIES:^7-10

i) Angle of Repose (Ө):

The frictional force in powder can be measured by the angle of repose. It is the maximum angle possible between the surface of pile of powder and the horizontal plane.

The blend that has angle of repose between 20⁰-30⁰is best for compression as it has good flow property. Angle of repose is calculated by fixed funnel method. In this method funnel was fixed to a stand in such a way that the lower tip of funnel was 2.5 cm above the surface. A graph paper was placed on the flat surface. The blend was allowed to fall freely on the graph paper through the funnel, till the tip of heap formed just touches the funnel. The radius of heap was noted and from this angle of repose was determined.

The angle of repose was determined using following equation,

tan θ =h/r

θ = tan-1 (h/r)

Where, h = height of pile (cm)

r = radius of the base of pile (cm)

ii) Bulk Density :

Bulk density is defined as the mass of powder divided by bulk volume. It is calculated using the following equation,

Bulk density = weight of sample taken / volume noted

A sample of about 2.5 gm was poured into 10ml-graduated cylinder. The cylinder was dropped at 2-second intervals onto a hard wooden surface three times, from a height of one inch. The volume was recorded and the bulk density was calculated.

iii) Tapped density:

It was determined by placing a graduated cylinder, containing a known mass of drug excipients blend on mechanical tapping apparatus, which was operated for a fixed no. of taps until the powder bed volume has reached a minimum.

The taped density was calculated by using the following formula

ρt = M/Vt

Vt =minimum volume (cm3)

M= the weight of blend(gm)

ρt=tapped density

iv) Carr’s Index:

The Compressibility Index of the powder blend was determined by Carr’s compressibility index. It is a simple test to evaluate the BD and TD of a powder and the rate at which it is packed down. The formula for Carr’s Index is as below,

Where,

LBD = Loose Bulk Density

TBD = Tapped Bulk Density

v) Hausner ratio:

The Hausner’s ratio is a number that is correlated to the flowability of a powder or granular material. The Hausner ratio of the powder was determined by the following equation:

Hausner ratio = TBD / LBD

POST-COMPRESSIONAL STUDIES:^11-13

i) General appearance:

The fast dissolving tablets, morphological characterization which includes size, shape, colour, presence or absence of odour, taste surface texture was determined.

ii) Thickness and diameter:

Five tablets were picked from each formulation randomly and thickness and diameter was measured individually. It is expressed in mm and standard deviation was also calculated. The tablet thickness and diameter was measured using vernier calliper.

iii) Hardness:

Hardness indicates the ability of a tablet to withstand mechanical shocks while handling. The hardness of the tablets was determined using Monsanto hardness tester. It is expressed in kg/cm². Five tablets were randomly picked and hardness of the same tablets from each formulation was determined. The mean and standard deviation values were also calculated.

iv) Friability test:

Friability test is performed to assess the effect of friction and shocks, which may often cause tablet to chip, cap or break. Roche Friabilator was used for the purpose. Pre-weighed sample of ten tablets were placed in the Friabilator, which was then operated at 25 rpm for 4 minutes or ran upto 100 revolutions. After 100 revolutions the tablets were dusted and reweighed. Compressed tablets should not lose more than 1% of their weight.

The % friability was then calculated by the following formula:

Percentage friability = (Initial weight - Final weight /Initial weight) × 100

vi) Weight variation:

20 tablets were selected randomly from each formulation and weighed individually to check for weight variation. The US Pharmacopoeia allows a little variation in the weight of a tablet.

vii) Drug content uniformity:

The tablets were tested for their drug content uniformity. At random 20 tablets were weighed and powdered. The powder equivalent to 10 mg was weighed accurately and dissolved in 100ml of 0.5% of Sodium Lauryl Sulphate (SLS) in water. The solution was shaken thoroughly. The undissolved matter was removed by filtration through Whatmann No.41 filter paper. Then the serial dilutions were carried out. The absorbance of the diluted solutions was measured at 342 nm. The concentration of the drug was computed from the standard curve of the Montelukast sodium in 0.5% of SLS in water.

viii)Wetting time and water absorption ratio:

A piece of tissue paper folded twice was placed in a small petridish (i.d = 6.5 cm) containing 6 ml of 0.5% SLS. A tablet was placed on the paper and the time required for complete wetting was then measured.

The water absorption ratio, R, was determined using the following equation,

R = Wa - Wb / Wb × 100

Where,

Wb is the weight of the tablet before water absorption and

Wa is the weight of the tablet after water absorption.

ix) In vitro dispersion time:

In vitro dispersion time was measured by dropping tablets in a measuring cylinder containing 10ml of 0.5% SLS at 37±0.5°C. Three tablets from each formulation were randomly selected and in vitro dispersion time was performed.

x) In vitro disintegration time:

The disintegration time was performed by apparatus specified in USP at 50 rpm. 900 ml of 0.5%SLS was used as disintegration medium and the temperature of 37± 0.5°C and time in second taken for complete disintegration of the tablet.

xi) In vitro drug release studies:

In vitro release of montelukast sodium from tablets was determined by using USP XXIV paddle dissolution apparatus (Electrolab TDT-06P) at 50 rpm using 900 ml of 0.5%SLS and temperature was maintained at 37±0.5° C throughout the study. 5 ml sample was collected at regular intervals for 30 min and the same volume of fresh medium was replaced. The samples withdrawn were filtered and drug content in each sample was analysed after suitable dilution by Shimadzu 1700 UV-Visible spectrophotometer at 342 nm.

xii) Data Analysis:

Various models were tested for explaining the kinetics of drug release. To analyze the mechanism of drug release rate kinetics of dosage form, the obtained data were fitted into zero-order, first order, Higuchi, Korsmeyer-Peppas release model and Hixson-Crowell equation.

xiii)Stability Studies:

It is the responsibility of the manufacturers to see that the medicine reaches the consumer in an active form. So the stability of pharmaceuticals is an important criterion. Stability of a drug has been defined as the ability of a particular formulation, in a specific container, to remain within its physical, chemical, therapeutic and toxicological specifications.

ICH specifies the length of study and storage conditions:

Long term testing

25°C ± 2°C / 60% ± 5% RH for 12 months

Accelerated testing

40°C ± 2°C / 75% ± 5% RH for 12 months

In present study, stability studies were carried out at 25°C ± 2°C / 60% ± 5% RH and 40°C ± 2°C / 75% ± 5% RH for a period of 60 days for the selected formulations. The formulations were then evaluated for changes in the physicochemical properties, wetting time, in vitro disintegration time and in vitro drug release.

RESULTS AND DISCUSSION:

Drug-excipients compatibility studies:

Fourier Transform Infrared (FTIR) Spectroscopy

The FTIR spectra showed similar characteristic peaks at their respective wavelengths with minor differences. The similarity in the peaks indicated the compatibility of drug with formulation excipients. The FTIR spectrum of pure Montelukast sodium and Montelukast sodium with excipients are shown below(Figure 1-4).

Table 3: Pre compression evaluation of drug/excipient mixture containing microcrystalline cellulose as diluent

Formulation Code	Angle of Repose	Bulk Density (gm/cc)	Tapped Density (gm/cc)	Carr’s Index (%)	Hausner’s Ratio
M1	25.75	0.47	0.54	12.96	1.14
M2	24.89	0.45	0.51	11.76	1.13
M3	27.01	0.53	0.62	14.51	1.16
M4	28.68	0.44	0.50	12	1.13
M5	24.14	0.45	0.52	13.46	1.15
M6	23.93	0.53	0.60	11.66	1.13
M7	26.09	0.46	0.52	11.53	1.13
M8	27.39	0.45	0.51	11.76	1.13
M9	24.8	0.50	0.59	15.25	1.18
M10	25	0.47	0.54	12.96	1.14
M11	27.02	0.43	0.49	12.24	1.13
M12	27.8	0.53	0.62	14.51	1.16

Table 4: Pre compression evaluation of drug/excipient mixture containing Lactose as diluent

Formulation Code	Angle of Repose	Bulk Density (gm/cc)	Tapped Density (gm/cc)	Carr’s Index (%)	Hausner’s Ratio
L1	26.21	0.45	0.52	13.46	1.15
L2	24.81	0.52	0.66	21.21	1.26
L3	28.23	0.53	0.70	24.28	1.32
L4	29.01	0.57	0.72	20.83	1.26
L5	26.75	0.44	0.55	20	1.25
L6	25.53	0.52	0.65	20	1.25
L7	27.34	0.55	0.72	23.61	1.30
L8	28.50	0.58	0.78	25.64	1.34
L9	25.46	0.47	0.55	14.54	1.17
L10	25.71	0.49	0.63	22.22	1.28
L11	26.60	0.58	0.76	23.68	1.31
L12	27.25	0.47	0.55	14.54	1.17

POST-COMPRESSIONAL PARAMETERS:

All the tablet formulations were evaluated for parameters such as shape, colour, thickness, hardness, friability, weight variation, drug content, in vitro disintegration time, in vitro dispersion time, wetting time, in vitro dissolution studies, model fitting of release profile and stability studies.

a) General appearance:

All the fast dissolving tablets from each batch were found to be flat, white in colour, circular in shape and having good physical appearance. There was no change in the colour and odour of the tablets from all the batches.

b) Thickness and diameter:

The range for tablets of montelukast sodium ranged from 3.12 ± 0.01 to 3.16 ± 0.03mm respectively. The standard deviation values indicated that all the formulations were within the range.

c) Hardness:

The hardness of all the tablets prepared by direct compression methods was maintained within the range of 3.3 ± 0.23 to 3.9 ± 0.23 kg/cm². The obtained results revealed that the tablets were having good mechanical strength and compactness.

d) Friability:

The friability was found for montelukast sodium in the range 0.23 to 0.38% within the approved range (<1%) which indicates the tablets had good mechanical resistance.

e) Weight variation:

The weight variation was found in the range of 149.83±0.36 to 150.92±0.41 mg for montelukast sodium. The weight variation results revealed that average percentage deviation of 20 tablets of each formula was less than ±7.5% i.e. in the Pharmacopoeial, limits which provide good uniformity in all formulations.

f) Drug content:

To evaluate a tablet’s potential for efficacy the amount of drug in the tablet need to be monitored from tablet to tablet and batch to batch. The percentage drug content was found to be in the range of 98.3 ± 0.50to 99.85 ± 0.62%.

g) Wetting time:

Wetting time is an important parameter related to water absorption ratio, which needs to be assessed to give an insight to the disintegration properties of the tablets. Water absorption ratio for these formulation batches varied in the following decreasing order:

Crosspovidone > Crosscarmellose sodium > Sodium starch glycollate

Formulation batches of M1-M12 wetting time was found between 26 to 47seconds and for L1 –L12 wetting time was found to be 30-50 sec.

h) Water Absorption Ratio:

Water absorption ratio, which is an important criterion for understanding the capacity of disintegrants to swell in presence of little amount of water, was calculated. The water absorption ratio increased with increase in the concentration of superdisintegrant from 2-8 %.The water absorption ratio found in the range between 54.21 ± 0.87to 79.83 ± 0.91% as MCC as diluent and 57.21 ± 0.87 to 73.83 ± 0.91% as lactose as diluent.

i) In vitro Disintegration Time:

In vitro disintegration time was found to be 32-53 sec as MCC as diluent and 37-58sec as Lactose as diluent.

j) In vitro Dispersion Time:

In vitro dispersion time was measured by the time taken to undergo uniform dispersion. All formulations showed rapid dispersion within seconds. In vitro dispersion time found to be 33-60 sec as MCC as diluent and 44-63 sec as lactose as diluent.

k) In vitro dissolution studies:

As the formulation batches M1 to M12 comprised of three different types of superdisintegrants, in vitro drug release at 25 minutes was found between 89.2 to 98.9% and for L1 to L12 found to be 87.2 to 97%.

Table 5: Post compression evaluation of formulated Montelukast sodium fast dissolving tablets containing microcrystalline cellulose as diluent

Formulation Code	Thickness (mm) (n=3)	Hardness (kg/cm²) (n=3)	Friability (%) (n=10)	Weight variation test (mg) (n=20)	Drug content (%) (n=3)
M1	3.12 ± 0.01	3.5 ± 0.24	0.36	149.91±0.22	98.70 ± 0.72
M2	3.15 ± 0.03	3.6 ± 0.25	0.32	149.83±0.36	98.55 ± 0.09
M3	3.16 ± 0.03	3.4 ± 0.27	0.38	150.21±0.49	99.30 ± 0.55
M4	3.14 ± 0.02	3.6 ± 0.23	0.23	150.92±0.41	99.76 ± 0.29
M5	3.14 ± 0.01	3.8 ± 0.25	0.26	150.16±0.32	98.65 ± 0.50
M6	3.15 ± 0.04	3.7 ± 0.26	0.33	149.95±0.91	98.58 ± 0.45
M7	3.12 ± 0.01	3.3 ± 0.24	0.28	150.51±0.99	98.28 ± 0.75
M8	3.14 ± 0.04	3.9 ± 0.23	0.34	150.60±0.60	98.90 ± 0.65
M9	3.14 ± 0.01	3.8 ± 0.24	0.31	150.01±0.58	99.46 ± 0.48
M10	3.15 ± 0.01	3.6 ± 0.25	0.23	150.51±1.02	99.35 ± 0.53
M11	3.14 ± 0.01	3.3 ± 0.23	0.28	150.03±0.59	99.85 ± 0.62
M12	3.13 ± 0.01	3.6 ± 0.24	0.34	150.01±0.59	98.51 ± 0.71

Table 6: Post compression evaluation of formulated Montelukast sodium fast dissolving tablets containing Lactose as diluent

Formulation Code	Thickness (mm) (n=3)	Hardness (kg/cm²) (n=3)	Friability (%) (n=10)	Weight variation test (mg) (n=20)	Drug content (%) (n=3)
L1	3.13 ± 0.01	3.2 ± 0.23	0.31	149.83±0.36	99.8 ± 0.7
L2	3.16 ± 0.03	3.4 ± 0.27	0.33	150.21±0.49	98.53 ± 0.09
L3	3.14 ± 0.02	3.6 ± 0.23	0.32	150.92±0.41	98.3 ± 0.50
L4	3.14 ± 0.01	3.8 ± 0.25	0.26	150.16±0.32	99.25 ± 0.25
L5	3.14 ± 0.01	3.8 ± 0.24	0.27	149.91±0.22	98.40 ± 0.54
L6	3.15 ± 0.03	3.6 ± 0.25	0.35	150.60±0.60	98.40 ± 0.47
L7	3.16 ± 0.03	3.4 ± 0.27	0.27	150.01±0.58	99.35 ± 0.70
L8	3.15 ± 0.04	3.6 ± 0.23	0.36	150.51±1.02	98.9 ± 0.65
L9	3.12 ± 0.01	3.3 ± 0.24	0.34	150.03±0.59	99.5 ± 0.43
L10	3.15 ± 0.03	3.5 ± 0.27	0.27	150.01±0.59	99.3 ± 0.53
L11	3.16 ± 0.03	3.2 ± 0.25	0.23	150.92±0.41	98.7 ± 0.68
L12	3.13 ± 0.01	3.4 ± 0.23	0.30	150.16±0.32	98.31 ± 0.75

Figure 5: Comparison between wetting time and water absorption ratio of formulated Montelukast sodium fast dissolving tablets containing MCC as diluent

Figure 6: Comparison between wetting time and water absorption ratio of formulated Montelukast sodium fast dissolving tablets containing Lactose as diluent

Figure 7: Comparison between wetting time and in vitro disintegration time of formulated Montelukast sodium fast dissolving tablets containing MCC as diluent

Figure 8: Comparison between wetting time and in vitro disintegration time of formulated Montelukast sodium fast dissolving tablets containing Lactose as diluent

Figure 9: In vitro disintegration time and in vitro dispersion time of Montelukast sodium fast dissolving tablets containing MCC as diluent

Figure 10: In vitro disintegration time and in vitro dispersion time of Montelukast sodium fast dissolving tablets containing Lactose as diluent

Figure 11: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing MCC + SSG (M1-M4)

Figure 12: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing MCC + CCS (M5-M8)

Figure 13: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing MCC + CP (M9-M12)

Figure 14: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing Lactose + SSG (L1-L4)

Figure 15: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing Lactose + CCS (L5-L8)

Figure 16: Plots of cumulative % drug release as a function of time for formulated Montelukast sodium fast dissolving tablets containing Lactose + CP (L9-L12)

l) Data Analysis:

The results of in vitro dissolution studies obtained from optimized formulations were plotted in Zero order, First order, Higuchi and Korsmeyer-Peppas release model and Hixson-Crowell equation to study the mechanism of drug release. The correlation coefficient (r) for drug release kinetic models was tabulated in table 7. The formulations M12 and L12 showed Hixson Crowell and First order which described the drug release, as a diffusion process based on the Fick’s law, square root time dependent.

m) Stability Studies:

Stability studies of formulation M12 and L12 was performed at 25°C ±2°C /60% ± 5% RH and 40°C ± 2°C /75% ± 5% RH for a period up to 60 days. The formulations were selected for stability studies on the basis of their high percentage cumulative drug release and also results of in vitro disintegration time, wetting time and in vitro dispersion studies.

There was no change in colour and shape of the tablets when stored at 25°C ± 2°C /60% ± 5% RH and 40°C ±2°C /75% ±5% RH and observed every 20 days interval up to 60 days. Formulations M12 and L12 showed not much variation in any parameter. From these results it was concluded that formulations were stable and retained its original properties.

Figure 17:Cumulative %drug released from formulation M12 and L12 stored at 25°C ± 2°C /60% ± 5% RH after 60 day

Figure 18:Cumulative %drug released from formulation M12 and L12 stored at 40°C ± 2°C /75% ± 5% RH after 60 day

CONCLUSION:

From the study conducted and from the observations and the results obtained thereof, following conclusions were drawn:

· The fast dissolving tablets of Montelukast sodium was successfully developed and evaluated. FTIR studies concluded that drug and excipients were compatible with each other.

· The formulated tablets were satisfactory in terms of hardness, thickness, friability, weight variation, drug content, wetting time, water absorption ratio, in vitro disintegration time, in vitro dispersion time and in vitro drug release.

· Formulation containing superdisintegrant Crosspovidone showed least wetting time and in vitro disintegration time.

· As the superdisintegrant concentration increases, the wetting time and in vitro disintegration time on tablets decreases.

· The formulation M12 was found to be the best on the basis of wetting time, in vitro disintegration time and in vitro drug release.

· The formulation M12 and L12 containing Crospovidone (8%) as superdisintegrant and microcrystalline cellulose and lactose as diluents was respectively found to be the optimized combination.

ACKNOWLEDGEMENT:

The authors are thankful to Management, Principal and Staff members of Karavali College of Pharmacy, Mangalore for providing necessary facilities.

REFERENCES:

1. Rajkumar G, Satyendra SB, Ashish P, Kshamashil S, Gourav T and Rituraj S. A Review on Formulation & Evaluation of Orodispersible Tablets. WJPR 2012; 1(3): 576-590.

2. Dineshmohan S, Vanitha K, Ramesh A, Srikanth G, Akila S. Formulation and Evaluation of Salbutamol Sulphate Fast Dissolving Tablet. IJRPBS 2010; 1(2): 105-108.

3. Jeevanadham S, Dhachinamoorthy D, Chandrashekar KB, Muthukumaran M, Sriram N, Joyasaruby J. Formulation and evaluation of naproxen sodium orodispersible tablets-A sublimation technique. Asian Journal of Biomedical and Pharmaceutical Sciences 2010;4 (1): 48-51.

4. Chang RK, Guo X, Burnside B, Couch R. Fast-dissolving tablets. Pharm Technol 2000; 24(6):52–58.

5. Bi Y, Sunada H, Yonezawa Y, Dayo K, Otsuka A, Iida K. Preparation and evaluation of compressed tablet rapidly disintegrating in oral cavity. Chem Pharm Bull (Tokyo) 1996; 44:2121-2127.

6. Praveen K, Kamlesh D. A Review: Fast Dissolving Drug Delivery System: Current Developments In Novel System Design and Technology. IJBAR 2012; 03(02): 82-98.

7. Indian Pharmacopoeia. The Controller of Publications, Ministry of Health and Family Welfare. New Delhi 1996: A-572-598.

8. Parodi B, RussoE, Caviglioli G,Caffagi G, Bignardi G. Development and characterization dosage form of oxycolon HCl. Drug Development Ind Pharm 1996: 22, 445-450.

9. Wang L, Tang S. A novel ketoconazole effervescent tablet for vaginal delivery. Int J Pharm 2008: 350,181-187.

10. John R, Dyer. Application of absorption spectroscopy of organic compounds. Indian edition. 2003: 33-38.

11. Nandgude T, Bhise K, Shinde V, Sharma D. Mouth dissolving tablet: geriatrics and paediatrics friendly drug delivery. Indian Drugs 2007; 4: 271-302.

12. United States Pharmacoepia. Asian Ed Convention Inc.2005: 233-45.

13. Gore S, Devarajan P. Mouth dissolving tablets Design of in vitro disintegration test. Ind J Pharm Sci 2000; 62(6): 508.

Received on 23.04.2016 Accepted on 17.05.2016

Asian J. Pharm. Res. 2016; 6(3): 159-169.

DOI: 10.5958/2231-5691.2016.00023.X

FORMULATION CODE	MATHEMATICAL MODELS (KINETICS)
FORMULATION CODE	Zero Order	First Order	Higuchi Matrix	Peppas	Hixson Crowell	Best Fit Model
M12	0.775	0.938	0.929	0.753	0.953	Hixson Crowell
L12	0.783	0.981	0.928	0.752	0.934	First order

Angle of repose (θ)

Bulk density:

Tapped density:

Carr’s consolidation index

Hausner ratio: