Formulation and in vitro Evaluation of Orodispersible ...

Journal of Pharmaceutical and Cosmetic Sciences Vol. 1(4) Pp. 53-56, 26 Dec. 2013 Available online at http://www.topclassglobaljournals.org ISSN 2315-8824 ©2013 Topclass Global Journals

Submitted 16/03/2013

Accepted 14/05/2013

Full Length Research Article

Formulation and in vitro Evaluation of Orodispersible tablet of Levosulpiride Imran Nazir1,2*, Jabbar Abbas1, Muhammad Asad1,2, Sajid Bashir1, Akhtar Rasul1, Nadeem Ahmad1,2, Muhammad Imran1 and Hafiz Muhammad Mazhar Asjad 1 1

Faculty of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan School of Pharmacy, The University of Faisalabad, Faisalabad 37610, Pakistan

2

******************************************************************************************************************************* ABSTRACT The objective of this study was to formulate and optimize an Orodispersible formulation of Levosulpiride. Levosulpiride Orodispersible tablet having D2-dopamine receptor antagonistic activity were made by direct compression using microcrystalline cellulose, mannitol, povidone and a disintegrant sodium starch glycolate. Thus, formulating Levosulpiride into an orodispersible dosage form would provide fast relief. The tablets were evaluated for weight variation, drug content, content uniformity, hardness, friability, water absorption ratio, in vitro and in vivo disintegration time and in vitro drug release. The results show that the presence of a superdisintegrant and mannitol is desirable for orodispersion. All the formulations satisfied the limits of orodispersion with a dispersion time of less than 60 sec, optimized drug released within 30 min and the formulations followed first order linear kinetics. So it is feasible to formulate orodispersible tablets of levosulpiride with acceptable disintegration time, rapid drug release and good hardness as an alternative to conventional tablet. Key words: Orodispersible, Levosulpiride, manitol, Microcrystalline Cellulose ******************************************************************************************************************************* INTRODUCTION Orodispersible drug delivery systems are extensively used to improve bioavailability and patient compliance nowadays (Deshpande and Ganesh, 2011). Many patients find it difficult to swallow tablets and hard gelatin capsules and thus do not comply with prescriptions that results in high incidence of non-compliance and ineffective therapy (Seager, 1998). Orodispersible tablets are gaining prominence as new drug delivery systems (Chang et al., 2000). Orodispersible dosage forms disintegrate in the aral cavity rapidly without chewing, thus releasing the drug which disperses in saliva (Bhushan et al., 2003). The faster the drug is in the solution, the quicker the absorption and onset of clinical effect (Bangale et al., 2011). Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down in to the stomach. In such cases, bioavailability of a drug is significantly greater than those observed from conventional tablet dosage form.

*Corresponding Author’s Email: [email protected]

Nazir et al. .... J. Pharm. Cosmet. Sci. 1(4) P 54

Figure 1. Chemical structure of Levosulpirirde

Table 1. Composition of different batches of Orodispersible tablet of Levosulpiride

Formulation

Levosulpiride(mg)

Avicel 200(mg)

Primojel (mg)

Mag. Stearate (mg)

Aerosil 200 (mg)

Povidone K30 (mg)

Mannitol(mg)

T-01

25

143

2

5

0.50

4

20

T-02

25

141

5

3

1.00

3

22

T-03

25

136

8

3

1.00

3

24

T-04

25

135

10

1.5

1.00

2

25

In this study, an effort has been made to formulate orodispersible tablets of Levosulpiride using different disintegrants. Levosulpiride is chemically N-[[(2S)-1Ethylpyrrolidin-2-yl] methyl]-2-methoxy-5sulfamoylbenzamide having molecular formula C15H23N3O4S with molecular weight 341.43 as described in Figure 1. It is a white crystalline powder with melting point 177-1810C and soluble in water and ethanol. Levosulpiride having D2-dopamine receptor antagonistic activity gives antidepressive and antiulcer effects (Martindale, 2006; Mucci et al., 1995; Ren et al., 2008), antiemetic and antidyspeptic effects and lower acute toxicity (Lozano et al., 2007). MATERIALS AND METHODS Levosulpiride, Microcrystalline cellulose, povidone, sodium starch glycolate was received as a gift sample from Saffron Pharma Faisalabad, Pakistan. All other materials like mannitol, magnesium stearate, Aerosil 200 used were of analytical grade and were commercially procured.

tablets of 200 mg weight using single punch tablet compression machine (Cadmach machinery Limited, Ahmadabad) as given in Table 1. Before the compression of tablets, the mixture blends of all the formulation were subjected for pre-compression parameter like Bulk density, Tapped density, Angle of Repose, percentage compressibility and Hausner ratio (Chowdary and Rama., 2000; Radke et al., 2009).

Evaluation of Tablets Weight variation Twenty tablets were selected at random and weighed individually. The individual weights were compared with the average weight for determination of weight variation. 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 noted.

Preparation of Orodispersible tablets Friability Levosulpiride orodispersible tabletes were prepared by direct compresion method. A total number of 4 formulations were prepared. All the ingredients were passed through 60-mesh sieve separately and collected. The drug and Avicel 200 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 9 mm size punch to get a

10 tablets were weighed and placed in a Roche friabilator and the equipment was rotated at 25 rpm for 4 min (Jashanjit and Rajmeet, 2009). The tablets were taken out, dedusted and reweighed. The percentage friability of the tablets was using the following formula: Percentage friability =Initial weight – Final weight x 100 Initial weight


Table 2. Micromeritic properties of mixture blend

Formulation Angle of Repose Bulk density (g/ml) Tapped density (g/ml) Carr’s Index(%) T-01 31.00 ± 0.18 0.710 ±0.02 0.852 ± 0.001 14.19 ±0.02 T-02 28.65 ± 0.09 0.760 ±0.05 0.839 ± 0.003 14.11 ±0.04 T-03 28.32 ± 0.18 0.735 ±0.01 0.880± 0.002 14.26 ±0.03 T-04 27.51 ± 0.18 0.761 ±0.04 0.895± 0.006 14.17 ±0.06

Hausner ratio 1.18±0.02 1.14±0.06 1.17±0.03 1.18±0.01

Table 3. Evaluation of orodispersible tablet of Levosulpiride

Formulation

Weight per Tablet (mg)

Weight Variation (mg)

T-01 T-02 T-03 T-04

200 200 200 200

201 203 201 200

Thickness (mm) 3.75 3.70 3.80 3.75

In vitro Dispersion Time Tablet was put into 100 ml distilled water at 37 ± 20C. Time required for complete dispersion of a tablet was measured with the help of digital tablet disintegration test apparatus (Kimura et al., 1992).

Hardness (Kg) 4.02 4.00 4.20 4.50

Friability (%) 0.16 0.17 0.13 0.15

D. Time (sec) 75 65 63 20

Assay Content (%) 98.68 98.93 99.2 99.5

dissolution medium. The temperature of the dissolution medium was maintained at 37 ±0.5 0C. An aliqout (5 ml) of dissolution medium was withdrawn at specific time intervals, filtered and suitably diluted prior to spectrophotometric analysis. Absorption of the solution was measured by UV spectroscopy (Shimadzu-1800, Japan) at 214 nm

Content uniformity Tests Standard Preparation

Statistical Analysis

Accurately weighed quantity (25mg) of Levosulpiride working standard taken in 100 ml volumetric flask. Dissolved and diluted up to the mark with 0.1N NaOH solution and stirred well to completely dissolve the powder. Next is the sonication and filtering of the solution and the absorbance measured at 214nm wavelength using 0.1N NaOH as blank (Prasad et al., 2009).

Statistical analysis was performed with Graph Pad Instat 3 software. All the tests were run in triplicate (n = 3). Experimental results were expressed as mean ± SD, and analyzed by one-way ANOVA for drug release data. Statistical significance was set at p< 0.05. RESULTS AND DISCUSSION

Sample Preparation 20 tablets weighed from each formulation are triturated in mortar using a pestle. An accurately weighed powder equivalent to 25mg of Levosulpiride in 100ml volumetric flask is taken. This is dissolved and diluted up to the mark with 0.1N NaOH solution. It is stirred well to completely dissolve the powder before being filtered, diluted and sonicated. The absorbance is measured at 214 nm wavelength using 0.1N NaOH as blank. In vitro drug release In vitro drug release studies were carried out using USP type II apparatus at 50 rpm. Phosphate buffer (900 ml) at pH 6.41 (corresponding to salivary pH) was used as the

Orodispersible/Mouth dissolving tablets of Levosulpiride were prepared by direct compression method using sodium starch glycolate used as super disintigrant and microcrystalline cellulose as diluent along with directly compressible mannitol, which serves as a sweetening agent and helps in masking taste of the drug. The material used for formulations were free flowing having Carr’s index less than 15% and angle of repose i.e less than 30o as mentioned in Table 2. This was further confirmed by Hausner’s ratio (1.2). The tablets obtained were of uniform weight with a range of 199-204 mg which was in acceptable range as described in specifications (±7.5%) thus indicating consistency in preparation of tablets and minimal batch to batch variations. Drug content was found to be in the range of 98.6299.5%, which is within acceptable limits. Hardness of the


Figure 2. In vitro release profile of Orodispersible tablets of Levosulpiride

tablets was found to be 4.0 to 4.5 kg/cm² and did not show any significant difference among various formulations. Friability below 1% was an indication of good mechanical resistance of the tablets as described in Table 3. Results indicated that there were no significant difference (p < 0.05) among four formulations (T-01-T-04) in terms of their physical properties which was further supported by Jashanjit and Rajmeet, 2009. All the formulations complied with the dispersion time requirement of ≤ 60 sec for Orodispersible tablets (European Pharmacopoeia., 2005). Formulation T-04 was found to be promising and displayed an in vitro dispersion time of 20 sec, which facilitates faster dispersion in the mouth. All the formulation showed the optimized drug released within 30 min (Figure 2) and the formulations followed first order linear kinetics. CONCLUSION All the optimized formulations (T-01 – T-04) showed disintegration times that were less than 60 sec, as well as good physicochemical properties. Drug release rates of the orodispersable tablets were much higher than that of the conventional tablets. The results indicates orodispersible tablets exhibits good in vitro disintegration as well as improved drug release rate and follow the first order release pattern. Thus the present study demonstrated potentials for rapid absorption, improved bioavailability, effective therapy and patient compliance. ACKNOWLEDGEMENT The authors wish to thank Saffron Pharma Faisalabad, Pakistan for providing Levosulpiride and necessary facilities to carry out the research work.

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