INTRODUCTION:

Oral route of administration is still continue to be the most preferred route due to its manifold advantages including ease of ingestion, pain avoidance, versatility and most importantly patient compliance, the most popular dosage form being tablets and capsules. One important drawback of such dosage forms is Dysphagia, or difficulty in swallowing is common among all age groups.

To fulfill these medical needs, pharmaceutical technologists have developed a novel oral dosage form known as ODTs which disintegrate rapidly in saliva, usually within a matter of seconds, without the need of water. Drug dissolution and absorption, as well as onset of clinical effect and drug bioavailability, may be significantly greater than those as compared with conventional dosage forms. The convenience of administration and improved patient compliance are important in the design of oral drug delivery system which remains the preferred route of drug delivery inspitr of various disadvantages.^1-4

Orodispersible tablets are also called as orally disintegrating tablets, mouth-dissolving tablets, rapid dissolving tablets, fast-disintegrating tablets, fast-dissolving tablets Recently, European Pharmacopoeia has used the term orodispersible tablet for tablets that disperses readily and within 3 min in mouth before swallowing United States Food and Drug Administration defined ODT as “A solid dosage form containing a medicinal substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed upon the tongue.” The disintegration time for ODTs generally ranges from several seconds to about a minute^5-7Superdisintegrants are used to improve the efficacy of solid dosage forms. This is achieved by decreasing the disintegration time which in turn enhancesdrug dissolution rate.⁸

Levamisole hydrochloride is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infections in both humans and animals (Tripathi, 2008; Moens, 1978). As an anthelmintic, it probably works by targeting the nematode nicotinergicacetylcholine receptor. Levamisole is available in dose of 50mg and 150 mg. In present work, 50 mg levamisole is taken.⁹ The aim of the study was to formulate an orodispersible tablet of Levamisole hydrochloride using different superdisintegrants separately.

MATERIALS AND METHOD:

Levamisole Hydrochloride was obtained as a gift sample from Medispray, Satara. Crosspovidone, Sodium starch glycolate, Sodium alginate, Mannitol, Microcrystalline cellulose, Aspartame, and Magnesium stearate all other ingredients were used on analytical grade.

Standard calibration curve for Levamisole HCl:

Dissolve 10 mg of drug in a solution containing 2 ml of ethanol and 8 ml of distilled water. Pipette out 1 ml from this solution and dilute with distilled water upto 10 ml. Then pipette out sufficient quantity of this solution and dilute with distilled water to get concentrations of 5 ppm, 10 ppm, 15 ppm, 20 ppm & 25 ppm. Then carry out UV sphectrophotometric determination by using Uv spectrophotometer at 214 nm note down the absorbance Plot a graph of absorbance against concentration.

Drug-excipient compatability study:

The spectrum analysis of pure drug, polymer and physical mixtures of drug and different excipients used for preparation of tablets was studied by FTIR. (Jasco 4600, Japan) The sample was mounted in IR spectrophotometer and the spectrum was recorded

PRECOMPRESSION STUDIES^10,11

All the physical parameters namely, angle of repose, bulk density, compressibility index and Hausner’s ratio were performed and the results were shown in table 2.

1. Angle of Repose:

It is the maximum angle possible between the surface of a pile of powder and the horizontal plane. Angle of Repose was determined by the funnel method. Accurately weighed powder blend was taken in the funnel. Height of the funnel was adjusted in such a way the tip of the funnel just touched the apex of the powder blend. Powder blend was allowed to flow through the funnel freely on to the surface. Diameter of the powder cone was measured and angle of repose was calculated using the given formula,

θ= tan ^-1 (--------)

2. Bulk density:

It is the ratio of total mass of powder to the bulk volume of powder. Required quantity of powder blend was transferred in 100 ml graduated cylinder and the bulk density was calculated by using the formula given below,

Weight of Powder

Bulk Density = ---------------------

Bulk Volume

3. Tapped density:

It is the ratio of total mass of powder to the tapped volume of powder. Required quantity of powder blend was transferred in 100 ml graduated cylinder which was operated for fixed number of taps until the powder blend volume has reached a minimum Tapped density using the was calculated by formula given below,

Weight of Powder

Tapped Density = ---------------------

Tapped Volume

4. Compressibility Index:

It is a simple test to evaluate bulk and tapped density of a powder. The formula for Carr’s index is as below,

Tapped Density - Bulk Density

Tapped Density = ----------------------------------- X 100

Tapped Density

5. Hausner’s Ratio:

Hausner’s Ratio is a number that is correlated to the flow ability of a powder,

Tapped Density

Housner's Ratio = -------------------------

Bulk Density

Table 1. Formulation Table

Formulation Code	Drug (mg)	CP (mg)	SSG (mg)	SA (mg)	Mannitol (mg)	MCC (mg)	Aspartame (mg)	Mg Stearate (mg)	Talc (mg)	Total wt (mg)
L1	50	5	--	--	70	60	10	3	2	200
L2	50	10	--	--	70	55	10	3	2	200
L3	50	15	--	--	70	50	10	3	2	200
L4	50	--	5	--	70	60	10	3	2	200
L5	50	--	10	--	70	55	10	3	2	200
L6	50	--	15	--	70	50	10	3	2	200
L7	50	--	--	5	70	60	10	3	2	200
L8	50	--	--	10	70	55	10	3	2	200
L9	50	--	--	15	70	50	10	3	2	200

Formulation of Orodispersible Tablets:

Levamisole Hydrochloride orodispersible tabletes were prepared by direct compression method according to formula given in the table 1. A total number of nine formulation were prepared. All the ingredients were passed through 60 mesh sieve seperately and collected. The drug and microcrystalline cellulose were mixed in small portion of both at each time and blended to get a uniform mixture and kept aside. Then the ingredients were weighed and mixed in geometrical order and the tablets were compressed using flat face 8 mm size punch to get a tablets of 200 mg weight using single punch tablet compression machine. Before tablets preparation, the mixture blends of all the formulation were subjected for compatibility studies (IR) and pre-compression parameter like Bulk density, Tapped density, Angle of Repose, percentage compressibility and Hausner’s ratio.

Post Compression Studies^12-14

Weight Variation:

Randomly, 20 tablets were selected after compression and the mean weight was determined. None of the tablets deviated from the average weight by more than ±7.5%.

Hardness:

The crushing strength of the tablets was measured using a Monsanto hardness tester. Three tablets from each formulation batch were tested randomly and the average reading ± SD was recorded

Thickness:

The diameter size and punch size of tablets depends on the die and punches selected for making the tablets. The thickness of tablet is measured by screw gauge. Tablet thickness should be controlled within a ± 5% variation of a standard value. In addition, thickness must be controlled to facilitate packaging.

Friability:

Twenty tablets were weighed and placed in a Roche friabilator and the equipment was rotated at 25 rpm for 4 min. The tablets were taken out, dedusted, and reweighed. The percentage friability of the tablets was calculated using below Eq.

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

Wetting Time:

Apiece of tissue paper (12×10.75 cm) folded twice was placed in a Petri dish (internal diameter=9 cm) containing 10 ml of buffer solution simulating saliva, pH 6.8, eosin. A tablet was placed on the paper and the time taken for complete wetting was noted. Three tablets from each formulation were randomly selected and the average wetting time was recorded.

In vitro disintegration time:

Disintegration time was measured using a modified disintegration method. For this purpose, a petri dish was filled with 10 ml of water at 37⁰ C±0.5⁰C. The tablet was carefully put in the centre of the petridish and the time for the tablet to completely disintegrate into fine particles was noted.

Content uniformity:

20 tablets were randomly selected and average weight was calculated and powdered in a glass mortar. Powder equivalent to 50 mg of drug was weighed and dissolved in 100 ml of 6.8 pH phosphate buffer, filtered and drug content analyzed spectrophotometrically at 214 nm.

In vitro drug release studies:

In vitro drug release of levamisole hydrochloride orodispersible tablets was determined using USP Dissolution Apparatus II (Paddle type) (Labindia). The dissolution test was performed using 900 ml 6.8 pH phosphate buffer at 37 ± 0.5. The speed of rotation of paddle was set at 50 rpm. 5 ml samples were withdrawn at time points of 1, 2, 3, 4, and 5min and same volume was replaced with fresh media. Absorbance of solution was checked by UV spectrophotometer (Jasco) at a wavelength of 214 nm and drug release was determined from standard curve.

FTIR studies:

To study the presence of interactions between the active pharmaceutical ingredient and the selected polymers, FT-IR studies were undertaken. The FT-IR spectra are shown in Figure 2 to 5.

Table 2. Pre Compression parameters of Levamisole HCl tablet formulation

Formulation code	Angle of Repose (θ)	Bulk density (g/ml)	Tapped density (g/ml)	Carr’s Index (%)	Hausner`s Ratio
L1	32.54	0.4186	0.4866	13.97	1.16
L2	33.32	0.3750	0.4391	14.56	1.16
L3	31.36	0.4235	0.4933	14.13	1.16
L4	34.65	0.3873	0.4505	13.98	1.16
L5	35.58	0.3790	0.4395	13.70	1.15
L6	32.28	0.3956	0.4676	15.37	1.18
L7	33.64	0.3645	0.4296	12.28	1.17
L8	32.36	0.4012	0.4425	12.85	1.17
L9	35.35	0.3895	0.4722	13.98	1.18

Table 3. Post Compression Parameters of ODT of Levamisole HCl

Formulation code	Weight variation	Hardness (kg/cm2)	Thickness (mm)	Friability (%)	Wetting Time (sec)	In-vitro disintegration Time (sec)	Amount of drug content (%)
L1	200±0.9	3.6±0.47	3.19±0.9	0.73±0.01	40.8±1.04	45.3±1.53	98.14±1.66
L2	201±1.2	3.4±0.83	3.20±0.4	0.76±0.14	32.0±0.95	34.0±1.00	99.02±0.50
L3	199±0.9	3.5±0.84	3.18±0.6	0.79±0.11	20.4±1.15	28.6±1.22	95.92±0.05
L4	198±0.4	3.5±0.50	3.21±1.2	0.74±0.02	42.0±0.85	48.4±2.42	98.91 ±0.61
L5	202±1.2	3.5±0.65	3.18±0.9	0.78±0.07	35.0±1.35	36.6±2.12	99.26±0.06
L6	198±0.4	3.4±0.43	3.22±0.4	0.80±0.09	29.4±1.48	32.6±1.25	99.86 ±0.84
L7	202±1.2	3.4±0.41	3.19±0.9	0.69±0.10	46.8±0.35	51.7±2.46	98.92 ±0.33
L8	199±0.4	3.6±0.87	3.21±1.2	0.65±0.04	34.7±1.45	35.5±0.50	99.43±0.05
L9	200±0.9	3.5±0.86	3.20±0.4	0.66±0.08	29.1±1.05	30.3±0.58	98.22±0.45

Table 4. In Vitro Drug Release data for Levamisole HCl Formulations (L1- L9)

Time (min.)	L1	L2	L3	L4	L5	L6	L7	L8	L9
2	32.19	31.49	46.18	24.67	35.25	31.77	23.67	31.21	32.23
4	51.16	59.06	62.04	48.32	52.34	48.64	39.64	44.78	48.60
6	72.63	73.43	79.63	66.64	69.66	67.25	58.44	61.32	64.34
8	81.24	83.44	85.33	75.44	85.97	86.52	79.56	78.25	81.22
10	97.44	97.24	98.93	89.58	96.44	95.17	90.44	91.64	96.64

Fig 6. In-vitro drug release profiles of ODT of Levamisole HCl (L1-L9)

Drug release pattern of levamisole HCl is show in fig.6. In the composition of batches as the concentration of superdisintegrants increases disintegration time of tablets minimizes and drug release becomes faster. L3 formulation was identified as best amongst all the other formulations and its release was found to be 98.93% within 10min.

CONCLUSION:

From the FT-IR spectra, the interference was verified and found that Levamisole HCl did not interfere with the excipients used. Precompression studies of Levamisole Hcl were performed. Orodispersible tablets of levamisole HCl were successfully prepared using crosspovidone, sodium starch glycolate and sodium alginate by using direct compression method. Post compression parameters like general appearance, weight variation, hardness, friability, wetting time and in vitro disintegration time indicate that values were within permissible limit for all formulations. In-vitro drug release study was carried out and based on the results, L3 formulation was identified as best amongst all the other formulations its disintegration time was found to be 28.6±1.22 sec and release was found to be 98.93% within 10min. On the basis of the results, the formulation containing crospovidone was considered as ideal among all other formulations used for the development of levamisole HCl tablets.

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Received on 16.05.2018 Accepted on 17.08.2018

Asian J. Pharm. Tech. 2019; 9(2):63-68.

DOI: 10.5958/2231-5713.2019.00011.4