Preparation and Evaluation of Mouth Dissolving Tablets of Loratadine by Direct Compression Method

 

M. Swamivelmanickam¹, P. Venkatesan², G. Sangeetha³

^1,2Department of Pharmacy, Annamalai University, Chidambaram, Tamil Nadu, India

³Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bangalore, Karnataka, India

 

ABSTRACT:

Loratadine, histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Administration of Loratadine through oral route is a challenge in children, who have difficulty to swallow tablets. In the present study, nine batches of Loratadine Mouth Dissolving tablets (MDTs) dosage form at the dose of 10 mg were formulated and evaluated. Results showed that thickness, weight variation, friability, hardness, and content uniformity of all five formulations were within the acceptable limits. But in the in-vitro dissolution study, formulation 7, 8 and 9 demonstrated better cumulative drug release than formulation 3 and 6. However, cumulative drug release of formulation 9 was comparable with innovator than formulation 3 and 6. Three month stability study of formulation 9 revealed that there were no significant change in physical parameters, drug content and dissolution profile. Hence the study concludes that Loratadine mouth dissolving tablets formulated using starch-1500 and microcrystalline cellulose (Formulation 9) showed better characteristics of mouth dissolving tablets.

 

 

INTRODUCTION:

Loratadine is a second-generation H1 histamine antagonist drug used to treat allergies. The tablet is most popular among all dosage forms existing today because of convenience of self administration, compactness and easy manufacturing. Many patients find it difficult to swallow tablet, especially in paediatrics and geriatric patients because of the physiological changes associated with them. Due to this dysphagia condition, they do not comply with prescription, which results in non-compliance with prescription.^[1] Thus MDTs are beneficial to patients who find it difficult to swallow tablet, moreover some of the drugs which are soluble in saliva are absorbed from the mouth and pharynx and oesophagus as the saliva passes down into the stomach, which enhances bioavailability by avoiding first pass metabolism.

 

 

Loratadine is used in the treatment of allergy. MDTs of this drug give better therapeutic benefits for the paediatric and bedridden or developmentally disabled patients Thus, MDTs would serve as an ideal dosage form for the patients as well as paediatric patients who find it difficult to swallow tablet. Due to its ease of use and high acceptability.^[2,3]   The objective of the present study was to formulate and evaluate the Loratadine MDTs by with super disintegrants by direct compression method.

 

MATERIALS AND METHODS:

Materials:

Loratadine was received as a gift sample from Sun Pharma, Mumbai, India. Sodium starch glycollate (SSG), Crospovidone, Croscarmellose sodium, Aerosil, Micro crystalline cellulose (MCC), Mannitol, Aspartame and Strawberry Flavor was received as gift samples from Axon drugs Pvt Ltd, Chennai, India. All other chemicals used were of analytical grade and were used without further purification.

 

Table No: 1- Formulation of Loratadine loaded MDTs

 

Preparation of the Standard Curve:

Calibration curve was prepared in 0.1N Methanolic HCl at λmax 275nm using UV- Visible Spectrophotometer for stock solution of 100mg/ml. Serial dilutions of 1, 3, 5, 7, 9μg/ml were prepared and absorbance was scanned in the range of 200-400nm against blank. The calibration curve was plotted.

 

Formulation of Tablets:

The MDTs of Loratadine were prepared by using direct compression method with the use of three different super disintegrants namely Maize starch, Sodium starch glycollate, Starch-1500 in the ratio of 5:4, 5:5 and 5:6. Micro crystalline cellulose, Mannitol was used as a diluent and a mixture of Aerosil and Magnesium stearate (5:1) was used as a glidant and lubricant respectively. Accurate quantity of drug and all ingredients were weighed according to the formula shown in Table No.1 except aerosil and magnesium stearate. The powder was blended homogeneously in a mortar and pestle for 15 minutes. Prepared powder blend was passed through sieve No. 60. Finally aerosil and magnesium stearate passed through sieve No. 30. This was added and further mixed for 10 minutes. The homogeneously mixed powder blend was compressed into a 16 stations Cad much tablet compression machine with 9mm, break through and flat faced punches with constant compression force and hardness. The same procedure was used for all the total nine formulations.^[7,12]

 

Evaluation of Granules:

Bulk density:

Apparent bulk density (ρb) was determined by pouring blend into a graduated cylinder. The bulk volume (Vb) and weight of the powder (M) was determined. The bulk density was calculated using the formula.

 

ρ b=Mass/Volume bor

 

BD = Weight of the powder/Volume of the powder.^[5,11]                                                  

 

Tapped density:

It was determined by placing a graduated cylinder, containing a known mass of the drug excipients blend, which was tapped for a fixed time until the powder bed volume has reached a minimum. The minimum volume (Vt) occupied in the cylinder and the weight (m) of the blend was measured. The tapped density (ρt) was calculated using the following formula.

 

ρt = m /V tor

 

TBD = Weight of the powder/Tapped volume of the powder.^[5,11]                                                 

 

Angle of Repose:

Angle of repose was determined using the cylinder method. The blend was poured through a funnel that can be raised vertically to a maximum cone height (h) was obtained. Radius of the heap (r) was measured and the angle of repose (θ) was calculated using the formula

 

θ = tan¯¹(r/ h) ^[5,11]                                                  

 

Compressibility Index:

The simplest way for the measurement of free flow of powder is compressibility, an indication of the case with which a material can be induced to how is given by compressibility index (I) which is calculated as follows

 Carr's compressibility index (%) = [(TBD-BD)/TBD x 100.^[5,11]                                                  

 

Hausner's ratio:

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

 

Hausner's ratio= ρt /ρb

 

Where, ρt is tapped density and ρb is bulk density. Hausner’s ratio is shown in Table No.1.

 

Evaluation of Loratadine MDTs:

Weight variation:

Twenty tablets were randomly selected from each batch and individually weighed. The average weight and standard deviation of 20 tablets were calculated. ^[5,11] The results are shown in Table No: 3.

 

Thickness uniformity:

Three tablets were selected randomly from each batch and thickness was measured by using Vernier Calliper^[5,11]  the results are shown in Table No: 3.

Hardness:

For each formulation, the hardness of 6 tablets was determined using the Monsanto hardness tester. The tablet was held along its oblong axis in between the two jaws of the tester. At this point, reading should be zero kg/cm². Then constant force was applied by rotating the knob until the tablet fractured. The value at this point was noted in kg/cm².^[5,11] The results are shown in Table No: 3.

 

Friability:

Friability of the tablets was determined using Roche Friabilator. Pre weighed sample of tablets was placed in the Friabilator and were subjected to 100 revolutions and droping the tablets at a height of 6 inches in each revolution. Tablets were dedusted using a soft muslin cloth and reweighed, the friability (F) is given by the formula^[5], and the results are shown in Table No: 3.

 

% F = (Initial weight. - Final weight./Initial weight.) x 100.

 

Content uniformity:

The tablet powder was weighed equivalent to 10mg of Loratadine and dissolved in 100ml of methanol and assayed for drug content using UV-Visible spectrophotometer at 275.00nm.^[8]

 

Disintegration time:

The test was carried out using USP Disintegration Test apparatus, (Veego scientific VTD-DV). The 6 tablets were introduced into each of six cylindrical tubes, the lower end of which was covered by a wire mesh. The tubes were then raised and lowered through a distance of 5.3 to 5.7cm in a test fluid phosphate buffer pH 6.8 and 0.1N HCl pH1.2 as a disintegrating media maintained at 37^°±2^° C. And the time   taken for disintegration of the tablet with no palpable mass remaining in the apparatus was measured in seconds.^[8,9]  The results are shown in Table No: 3.

 

Wetting time of water absorption Ratio:

A piece of tissue paper about 10cm folded twice was placed in small Petri dish of diameter 10cm containing 6 ml of water. A tablet was put on the paper and the time required for water to reach the upper surface of tablet was noted. For water absorption ratio the same wetted tablet was taken out from the petri dish and weighed.^[4,6]    The results are shown in Table No: 3.

 

Water absorption ratio (R) was determined by using the following equation.

 

R=Wa - Wb / Wb×100

 

Where,

Wb =Weight of tablet before water absorption

Wa = Weight of tablet after water absorption

 

In-vitro Dissolution studies ^[10,11]:

Dissolution profiles of Loratadine tablets were determined using the USP Type II Dissolution Test apparatus (Veego scientificVDA-8DR) set with a paddle speed of 100 RPM. Dissolution was performed in 900 ml of 0.1N HCl maintained at 37^°±0.5^°C. An aliquot of dissolution medium, 5ml was withdrawn at 3, 6, 9, up to 12 min with 5 minute interval, and filtered through Whatmann filter paper. The amount of drug dissolved was determined by UV-Visible spectrophotometer (Shimadzu-1700 UV-VIS Spectrophotometer) by measuring the absorbance of the sample at 275 nm. The results are shown in Table No: 4.

 

Uniformity of drug content:

One tablet was crushed and transferred to a 100ml volumetric flask, 20ml of methanol was added, shaken well to dissolve the drug. The volume was made up to 100ml with water and filtered. Then 5ml of the filtrate was diluted to 50ml with water again from that 5 ml was taken and diluted to 50ml with water. The amount of drug content was determined by UV-Visible spectrophotometer (Shimadzu-1700 UV-VIS Spectrophotometer) by measuring the absorbance of the sample at 275nm.^[8,12]  The results are shown in Table No: 3.

 

RESULTS AND DISCUSSION:

For the preparation of loratadine tablets starch-1500 and micro crystalline cellulose was selected as superdisintegrant. Before going for compression of the tablets the powder blend was evaluated in the pre-compression parameters. like angle of repose, bulk density, tapped density, Carr’s compressibility index and Hausner’s ratio to predict the flow properties of powders. All the formulations showed good and excellent flow properties. The evaluation of pre-compression studies of the powder blend was given in the Table 2. The fast dissolving tablets were prepared by direct compression method because of its cost effectiveness and due to less number of manufacturing steps. The post compression parameters like the hardness, thickness, friability, weight variation, disintegration time, wetting time; drug content and water absorption ratio were given in Table 3 and Table 4. The total weight of tablets was 200mg and it was observed that all the tablets are from 201.55mg – 205.15mg. And the hardness of all the formulations was observed to be 3.0- 3.38kg/cm². The percentage friability of all the formulations was found to be less than 1% to provide mechanically stable mouth dissolving tablets. As the mouth dissolving tablets must show immediate action all the tablets were found to be disintegrated less than one minute. The disintegration time taken in combination of both superdisintegrants was less compared to the individual concentration. The combination of superdisintegrants like starch-1500 and micro crystalline cellulose at high and equal concentration with F9 formulation took 11 seconds for disintegration when compared to low and equal concentration of F7 formulation which was disintegrated at 20 seconds. The water absorption ratio of tablets was found to be 87.24% - 120.80%. The percentage drug content of all the tablets was found to be between 97.75 – 99.45 %.

 

Figure 1: Calibration curve of Loratidine                               Figure 2: In-vitro Drug Release Profile of Loratadine MDTs

 

Table No: 2 Evaluation of Loratadine granules

 

Table No: 3  Various post compression parameters of the Formulations

 

Table No: 4 In vitro dissolution profile data for mouth dissolving Loratadine tablets for all formulations

CONCLUSION:

This present study of investigation can be concluded that the direct compression method showed better disintegration and drug release by using super disintegrants. The prepared tablets were disintegrating within few seconds without need of water. The direct compression technique would be an effective alternative approach compared with the use of more expensive adjuvants in the formulation of mouth dissolving tablets.

 

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Accepted on 14.12.2019           © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(6):2629-2633.