FORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLET
HTML Full TextFORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLET
Vishal Sahu* and B.V. Bakade
- Wadhwani College of Pharmacy, Amravti University, Amravti, Maharashtra, India
ABSTRACT
The objective of the present study was to develop venlafaxine hydrochloride orodispersible tablet by using conventional techniques which are simple and cost effective such as use of superdisintegrant technology. In this, sodium starch glycolate and Crosscarmellose sodium crosspovidone and kyron-T-314 were used in the rapid disintegration of the tablets. In this various trials were conducted for the selection of optimum concentration of superdisintegrant. The optimized formula aids in the stabilization of final product. The blend and compressed tablets were evaluated for physical characteristics like bulk density, tapped density, angle of repose, hardness, friability, disintegration time, wetting time, water absorption ratio, In-vitro dispersion time and chemical characteristics like In-vitro dissolution, content uniformity and assay. The stability study was conducted for the optimized batch. This design of dosage form will open a new era for rapid disintegration tablets.
Keywords: Rapid disintegration, Superdisintegrant, Venlafaxine, In vitro Dispersion Time
INTRODUCTION: Mouth dissolving drug delivery systems (MDDDS) are a new generation of formulations which combine the advantages of both liquid and conventional tablet formulations, and at the same time, offer added advantages over both the traditional dosage forms. It provides the convenience of a tablet formulation and allows the ease of swallowing provided by a liquid formulation. The formulations have special advantages for dysphasic, geriatric, pediatric, bed-ridden, travelling and psychotic patients who are unable to swallow or refuse to swallow conventional oral formulations. It do not require water for administration, thus are good alternative for travellers and for bed ridden patients 1.
In the recent past, several new advanced technologies have been introduced for the formulation of mouth dissolving tablets (MDTs) with very interesting features, like extremely low disintegration time, exceptional taste masking ability, pleasant mouth feel and sugar free tablets for diabetic patients. The technologies utilized for fabrication of MDDDS include lyophilization, moulding, direct compression, cotton candy process, spray drying, sublimation, mass extrusion, and quick dissolve film formation. These techniques are based on the principles of increasing porosity and/or addition of super disintegrants and water soluble excipients in the tablets.
The formulations prepared from these techniques differ from each other on the basis of the factors like mechanical strength of final product, drug and dosage form stability, mouth feel, taste, rate of dissolution of the formulation in saliva, rate of absorption from saliva and overall drug bioavailability. These products not only increase the patient‟s compliance but also fetch large revenues to manufacturers due to line extension of the existing formulation 2. Although, numerous technologies had been developed for the fabrication of these unique dosage forms in last two decades, but so far, no standardized technique has been designed or mentioned in pharmacopoeias for their evaluation except in European Pharmacopoeia (EP), which defines orodispersible tablets as “uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed”. European Pharmacopoeia also specifies that the orodispersible tablets should disintegrate within 3 minutes when subjected to conventional disintegration test used for tablets and capsules 3.
MATERIALS AND METHODS:
Materials: Venlafaxine Hydrochloride was obtained from Orchid Chemicals and Pharmaceuticals Ltd., Sodium starch glycollate and Crosscarmellose sodium were obtained from Rankem limited, Mumbai. Other excipients used in this formulation were of analytical grade.
Methods:
Preparation of Venlafaxine Orodispersible tablets: Venlafaxine Hydrochloride, Microcrystalline cellulose, Superdisintegrants, Aerosil, Aspartame, Mannitol, Starch-1500 were sifted through # 40 mesh separately, collected in poly bags. Venlafaxine hydrochloride, Microcrystalline cellulose, Super- disintegrants, Aerosil, Aspartame, Mannitol, Starch-1500, Strawberry flavor were loaded into Octagonal blender and mixed. Sodium saccharine, Magnesium stearate, Talc were added to this and mixed for 10 minutes, then sifted through #60 mesh.
Then, the final blend was compressed in to tablets using Rotary press tablet compression machine. The formula for the preparation of various baches of Venlafaxine hydrochloride tablets were given in table 1 and 2.
TABLE 1: COMPOSITION OF ALL THE FORMULATIONS (MD1-MD8)
Sr. No Ingredient (mg/tablet) MD 1 MD 2 MD 3 MD 4 MD 5 MD 6 MD 7 MD 8 1 Venlafaxine 25 25 25 25 25 25 25 25 2 Crosscarmellose sodium 5 10 15 20 - - - - 3 Sodium starch glycolate - - - - 5 10 15 20 4 Avicel 46 46 46 46 46 46 46 46 5 Mannitol 60 55 50 45 60 55 50 45 6 Talc 4 4 4 4 4 4 4 4 7 Aspartame 18 18 18 18 18 18 18 18 8 Aerosil 5 5 5 5 5 5 5 5 9 Magnesium stearate 2 2 2 2 2 2 2 2 10 Mint flavor 5 5 5 5 5 5 5 5 11 Total weight 170 170 170 170 170 170 170 170 TABLE 2: COMPOSITION OF ALL THE FORMULATIONS (MD9-MD16)
Sr. No Ingredient (mg/tablet) MD 9 MD 10 MD 11 MD 12 MD 13 MD 14 MD 15 MD 16 1 Venlafaxine 25 25 25 25 25 25 25 25 2 Kyron T-314 5 10 15 20 - - - - 3 L-HPC - - - - 5 10 15 20 4 Avicel 46 46 46 46 46 46 46 46 5 Mannitol 60 55 50 45 60 55 50 45 6 Talc 4 4 4 4 4 4 4 4 7 Aspartame 18 18 18 18 18 18 18 18 8 Aerosil 5 5 5 5 5 5 5 5 9 Magnesium stearate 2 2 2 2 2 2 2 2 10 Mint flavor 5 5 5 5 5 5 5 5 11 Total weight 170 170 170 170 170 170 170 170 Evaluation:
Pre-compression parameters: The Angle of repose, Bulk density, Tapped density, Compressibility Index, Hausner’s ratio and % LOD were determined and results were given in Table 3.
Post compression parameters: Thickness, Weight Variation Test, Hardness Test, Friability Test and Disintegration were determined as per the Standard Procedures and the results obtained are tabulated in Table 4 and 5 .
TABLE 3: PREFORMULATION STUDIES OF DIFFERENT TABLET FORMULATION
Formulation Angle of repose (ϴ) Bulk density (g/cc) Tapped density (g/cc) Carr’s index (%) Hausner ratio F1 32.15 ± 0.11 0.293 ± 0.16 0.418 ± 0.24 29.90 ± 0.14 1.42 ± 0.16 F2 30.46 ± 0.22 0.308 ± 0.35 0.450 ± 0.28 31.55 ± 0.18 1.46 ± 0.05 F3 31.56 ± 0.17 0.304 ± 0.18 0.450 ± 0.13 32.44 ± 0.25 1.48 ± 0.02 F4 33.46 ± 0.31 0.296 ± 0.24 0.422 ± 0.19 31.42 ± 0.33 1.42 ± 0.02 F5 32.61 ± 0.24 0.318 ± 0.27 0.441 ± 0.24 29.89 ± 0.37 1.38 ± 0.07 F6 32.26 ± 0.15 0.328 ± 0.34 0.465 ± 0.32 29.46 ± 0.28 1.41 ± 0.05 F7 34.33 ± 0.19 0.316 ± 0.25 0.438 ± 0.27 27.85 ± 0.26 1.38 ± 0.07 F8 33.42 ± 0.21 0.366 ± 0.26 0.55 ± 0.34 33.4 ± 0.34 1.36 ± 0.21 F9 32.51 ± 0.23 0.309 ± 0.41 0.452 ± 0.26 31.63 ± 0.21 1.46 ± 0.05 F10 31.62 ± 0.16 0.309 ± 0.31 0.042 ± 0.18 26.42 ± 0.16 1.35 ± 0.03 F11 30.67 ± 0.12 0.322 ± 0.24 0.446 ± 0.28 27.80 ± 0.21 1.38 ± 0.16 F12 30.71 ±0.22 0.307 ± 0.15 0.449 ± 0.33 31.62 ± 0.23 1.46 ± 0.21 F13 31.82 ± 0.32 0.328 ± 0.21 0.465 ± 0.38 29.46 ± 0.30 1.41 ± 0.07 F14 32.31 ± 0.17 0.316 ± 0.19 0.438 ± 0.34 24.85 ± 0.27 1.38 ± 0.06 F15 33.23 ± 0.14 0.318 ± 0.23 0.441 ± 0.26 29.89 ± 0.26 1.36 ± 0.21 F16 31.32 ± 0.19 0.366 ± 0.21 0.550 ± 0.28 33.45 ± 0 33 1.41 ± 0.19 TABLE 4: EVALUATION RESULT OF TABLET FROM BATCH MD1-MD16
Formulation Thickness (cm) Diameter (cm) Friability (%) Hardness (kg/cm2) MD1 0.384 ± 0.14 0.815 ± 0.19 0.60 ± 0.15 3.2 ± 0.23 MD2 0.410 ± 0.74 0.815 ± 0.13 0.60 ± 0.07 3.1 ± 0.14 MD3 0.410 ± 0.21 0.815 ± 0.26 0.29 ± 0.05 3.2 ± 0.74 MD4 0.411 ± 0.14 0.815 ± 0.33 0.88 ± 0.02 3.3 ± 0.47 MD5 0.409 ± 0.32 0.815 ± 0.53 0.60 ± 0.06 3.0 ± 0.51 MD6 0.410 ± 0.47 0.815 ± 0.11 0.29 ± 0.01 3.2 ± 0.54 MD7 0.409 ± 0.54 0.815 ± 0.16 0.60 ± 0.08 3.1 ± 0.63 MD8 0.409 ± 0.47 0.815 ± 0.22 0.88 ± 0.15 3.2 ± 0.71 MD9 0.410 ± 0.47 0.815 ± 0.37 0.60 ± 0.17 3.3 ± 0.62 MD10 0.410 ± 0.52 0.815 ± 0.41 0.29 ± 0.21 3.2 ± 0.19 MD11 0.409 ± 0.51 0.815 ± 0.29 0.29 ± 0.03 3.2 ± 0.27 MD12 0.410 ± 0.51 0.815 ± 0.17 0.88 ± 0.07 3.1 ± 0.54 MD13 0.409 ± 0.48 0.815 ± 0.13 0.29 ± 0.11 3.1 ± 0.36 MD14 0.409 ± 0.51 0.815 ± 0.14 0.88 ± 0.13 3.0 ± 0.54 MD15 0.410 ± 0.46 0.815 ± 0.35 0.60 ± 0.27 3.1 ± 0.49 MD16 0.410 ± 0.41 0.815 ± 0.43 0.88 ± 0.01 3.2 ± 0.51 TABLE 5: EVALUATION RESULT OF TABLET FROM BATCH MD1-MD16
Formulation Drug Content (%) Weight variation (mg) Disintegration time (min) Wetting time (sec) MD1 99.29 ± 0.51 171.3 ± 0.12 1.27 ± 0.01 26 ± 0.24 MD2 98.52 ± 1.08 171.6 ± 0.53 0.58 ± 0.02 28 ± 0.14 MD3 97.76 ± 1.26 169.8 ± 0.54 0.50 ± 0.14 25 ± 0.17 MD4 97.63 ± 0.51 170.3 ± 0.63 0.41 ± 0.25 30 ± 0.12 MD5 99.86 ± 0.33 172.5 ± 0.87 1.44 ± 0.14 31 ± 0.32 MD6 98.51 ± 0.94 171.8 ± 0.36 0.55 ± 0.14 30 ± 0.54 MD7 99.63 ± 0.86 171.1 ± 0.74 0.43 ± 0.36 29 ± 0.36 MD8 98.51 ± 0.63 172.2 ± 0.52 0.37 ± 0.15 28 ± 0.65 MD9 98.43 ± 0.71 171.1 ± 0.14 1.46 ± 0.14 26 ± 0.14 MD10 99.26 ± 0.54 173.3 ± 0.51 0.41 ± 0.13 28 ± 0.21 MD11 98.42 ± 0.46 170.6 ± 0.49 0.44 ± 0.27 27 ± 0.36 MD12 98.81 ± 0.51 170.8 ± 0.37 0.39 ± 0.21 26 ± 0.52 MD13 99.64 ± 0.29 169.9 ± 0.68 1.42 ± 0.11 29 ± 0.61 MD14 98.52 ± 0.38 173.5 ± 0.73 0.58 ± 0.07 24 ± 0.29 MD15 99.61 ± 0.41 172.8 ± 0.81 0.46 ± 0.13 26 ± 0.13 MD16 99.82 ± 0.51 172.1 ± 0.72 0.37 ± 0.11 28 ± 0.16
In vitro Drug Release: The tablets prepared from different batches are further evaluated for in-vitro drug release studies.
- Cumulative Percent Drug Release of batch from MD1-MD4:
TABLE 6: PERCENT DRUG RELEASE OF TABLET FROM BATCH MD1-MD4
Sampling time (minutes)
Cumulative percentage of drug release in 0.1 N HCl MD 1 MD 2 MD 3 MD 4 5 67.16 ± 0.26 72.09 ± 0.68 89.84 ± 0.43 93.78 ± 0.19 10 98.63 ± 0.33 99.68 ± 0.51 97.73 ± 0.39 98.70 ± 0.33 FIG. 1: COMPARISON OF CUMULATIVE PERCENT DRUG RELEASE FROM MD1 TO MD4
- Cumulative Percent Drug Release of batch from MD5-MD8:
TABLE 7 : PERCENT DRUG RELEASE OF TABLET FROM BATCH MD5-MD8.
Sampling time (minutes)
Cumulative percentage of drug release in 0.1 N HCl MD 5 MD 6 MD 7 MD 8 5 91.81 ± 0.21 92.80 ± 0.31 94.77 ± 0.12 95.75 ± 0.53 10 99.68 ± 0.29 97.73 ± 0.33 98.76 ± 0.17 96.75 ± 0.66 FIG. 2: COMPERISION OF CUMULATIVE PERCENT DRUG RELEASE FROM MD5 TO MD8
- Cumulative Percent Drug Release of batch from MD9-MD12:
TABLE 8: PERCENT DRUG RELEASE OF TABLET FROM BATCH MD9-MD12
Sampling time (minutes)
Cumulative percentage of drug release in 0.1 N HCl MD 9 MD 10 MD 11 MD 12 5 89.84 ± 0.63 88.85 ± 0.47 87.87 ± 0.39 91.81 ± 0.19 10 97.73 ± 0.59 99.80 ± 0.44 97.87 ± 0.21 98.86 ± 0.15 - FIG. 3: COMPARISON OF CUMULATIVE PERCENT DRUG RELEASE FROM MD9 TO MD12
- Cumulative Percent Drug Release of batch from MD13-MD16:-
TABLE 9 : PERCENT DRUG RELEASE OF TABLET FROM BATCH MD13-MD16.
Sampling time (minutes)
Cumulative percentage of drug release in 0.1 N HCl MD 13 MD 14 MD 15 MD 16 5 89.84 ± 0.88 91.81 ± 0.25 88.85 ± 0.78 87.96 ± 0.17 10 99.68 ± 0.76 99.76 ± 0.44 98.70 ± 0.45 98.87 ± 0.26 FIG. 4: COMPERISION OF CUMULATIVE PERCENT DRUG RELEASE FROM MD13 TO MD16
COMPATIBILITY STUDY:-
- FTIR of Venlafaxine Hydrochloride
- FIG. 5: FTIR OF VENLAFAXINE HYDROCHLORIDE
- FTIR of curve of Venlafaxine Hydrochloride and Kyron T-314
- FIG. 6: FTIR OF VENLAFAXINE HYDROCHLORIDE AND KYRON T-314
The result shows that there is no incompatibility was seen in between the drug Venlafaxine hydrochloride and excipients used. All the peak of drug venlafaxine hydrochloride were present in the IR spectrum of physical mixture drug and excipients.
Preparation of standard curve for venlafaxine hydrochloride in 0.1 N HCl: The stock solution is used to prepare 10ug/ml, 20ug/ml, 30ug/ml, 40ug/ml, 50ug/ml, 60ug/ml, 70ug/ml, 80ug/ml, 90ug/ml, 100ug/ml of venlafaxine in 0.1 N HCl and analysed at 274nm.
TABLE 10: STANDARD CURVE OF VENLAFAXINE HYDROCHLORIDE
Sr. No. Concentration (μg/ml) Absorbance (nm) 1 0 0 2 10 0.04 3 20 0.09 4 30 0.120 5 40 0.167 6 50 0.207 7 60 0.240 8 70 0.289 9 80 0.329 10 90 0.360 11 100 0.410 - FIG. 7: STANDARD CURVE OF VENLAFAXINE HYDROCHLORIDE
Correlation coefficient (R2) = 0.999, Equation of regression line y = 0.004x + 0.002
Where, x = value for concentration, y = regressed value of absorbance; 0.004= slope of regressed line; 0.002= y intercept
CONCLUSIONS:
- Sixteen Batches of Venlafaxine hydrochloride mouth dissolving tablets were prepared.
- Optimized Batch no MD-10 containing from Kyron T-314 (10%), Microcrystalline Cellulose, Mannitol, Aspartame, Aerosil, Magnesium Stearate and Talc showed 41 second disintegration time.
- Drug content of optimized batch MD-10 was found within the limits.
- In vitro dissolution studies of MD-10 demonstrated 99.80 % of drug release within 10 minutes.
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How to cite this article:
Sahu V and Bakade BV: Formulation and Evaluation of Mouth Dissolving Tablet. Int J Pharm Sci Res. 3(12); 4831-4837.
Article Information
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4831-4837
842
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English
Ijpsr
Vishal Sahu* and B.V. Bakade
P. Wadhwani College of Pharmacy, Amravti University, Amravti, Maharashtra, India
vishal1002feb@gmail.com
19 August, 2012
15 September, 2012
25 November, 2012
http://dx.doi.org/10.13040/IJPSR.0975-8232.3(12).4831-37
01 December, 2012