ISSN: 2348 –0882
==========================================================================
Int. J. Pharm. Res. Sci., 2014...
ISSN: 2348 –0882
==========================================================================
Int. J. Pharm. Res. Sci., 2014...
Table 1. Formulation of fast dissolving tablets using croscarmellose sodium
Ingredients in (mg)
SD complex
Croscarmellose ...
decrease in porosity. This increases the number of
interparticulate contacts and contacts areas and
causes an increase in ...
Ten tablets from each batch formulation were
from each formulation and weighed collectively
selected randomly and their th...
absorbance at 285 nm. Drug concentration was
IR Spectrum of Carbamazepine
calculated from the standard calibration curve a...
carbamazepine, physical mixture, solid dispersion,
Fourier Transform Infrared Spectroscopy

polymer and the formulation.

...
Figure 2. DSC thermogram of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) Solid
Dispersion E) Formulation F...
Peak height of pure carbamazepine was
selected to calculate the RDC of CBZ, best
physical mixture and solid dispersion. Wh...
Table 8. Evaluation of fast dissolving tablets.
Formulation code Weight variation
(mg)
Passes
F1
Passes
F2
Passes
F3
Passe...
Table 10. Data for disintegration time, drug content and Disintegration time of fast dissolving tablets
of carbamazepine.
...
Table 11. In vitro dissolution profile of formulationF1- F9.
Time
(min)

Cumulative drug release (%)
F1

F2

F3

F4

F5

F...
References:
1. Brahmankar DM, Jaiswal SB, 2005.
Biopharmaceutics and pharmacokinetics: a
treatise. 4th ed.: Delhi: Vallabh...
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Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using Solid Dispersion

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Abstract:
The purpose of present research work was to
optimize the formulation of fast dissolving tablet
of carbamazepine. Carbamazepine is one the most
prescribed antiepileptic drug. Fast dissolving
tablets of carbamazepine were prepared by using
different types of superdisintegrants like
croscarmellose sodium and sodium starch
glycolate. Fast dissolving tablet is prepared by
direct compression method. The formulations
were evaluated for wetting time, hardness,
friability, content uniformity, invitro
disintegration time, release profile. The result
revealed that the formulation F5 which containing
the 5% croscarmellose sodium as a
superdisintegrant have good dissolution profile
with shortest Disintegration time. It can be
concluded that the tablet of carbamazepine with
better pharmaceutical properties than conventional
tablets could be obtained using formulation F5.

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Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using Solid Dispersion

  1. 1. ISSN: 2348 –0882 ========================================================================== Int. J. Pharm. Res. Sci., 2014, 02(1), 47-59. www.ijprsonline.com Formulation and Evaluation of Fast Dissolving Tablets of Carbamazepine Using Solid Dispersion. Metkari VB1,*, Kulkarni LV1, Patil PS1, Jadhav PA1, Jadhav PH1, Yadav PS1. 1 College of pharmacy Medha Satara, Maharashtra, India. Corresponding author email: vmetkari@yahoo.com ---------------------------------------------------------------------------------------------------------------------------------Abstract: The purpose of present research work was to optimize the formulation of fast dissolving tablet of carbamazepine. Carbamazepine is one the most prescribed antiepileptic drug. Fast dissolving tablets of carbamazepine were prepared by using different types of superdisintegrants like croscarmellose sodium and sodium starch glycolate. Fast dissolving tablet is prepared by direct compression method. The formulations were evaluated for wetting time, hardness, friability, content uniformity, invitro disintegration time, release profile. The result revealed that the formulation F5 which containing the 5% croscarmellose sodium as a superdisintegrant have good dissolution profile with shortest Disintegration time. It can be concluded that the tablet of carbamazepine with better pharmaceutical properties than conventional tablets could be obtained using formulation F5. Keywords: Fast dissolving tablet, Croscarmellose sodium, sodium starch glycolate, Direct compression. Introduction: Oral route has been one of the most of popular routes of drug delivery due to its ease of administration, patient compliance, least sterility constraints and flexible design of dosage forms (Brahmankar et al., 2005).Many patient of different age group like geriatric and pediatric complaint of some solid dosage form because of difficulty in swallowing. So to solve this problem and increase patient compliance fast dissolving tablet is prepared. Fast dissolving tablets are those when put on tongue disintegrating instantaneously releasing the drug which dissolves or disperses in the saliva. Fast dissolving tablets are also called as mouth dissolving tablets, orodispersible tablets, rapi melts, porous tablets, quick dissolving etc. The faster the drug into solution, quicker the absorption and onset of clinical effects. Some drugs are absorbed from mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. According to European pharmacopoeia, the ODT should disintegrate in less than three minutes. The basic approach in development of fast dissolving tablets is the use of the superdisintegrants like crosscarmellose sodium and sodium starch glycolate. Which provide instaneous disintegration of the tablets after putting on tounge, their by release the drug in saliva. The bioavailability of some drug may be increased due to absorption of drug in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into stomach ( Abed et al., 2010). Fast dissolving tablets are those when put on tongue disintegrating instantaneously releasing the drug which dissolves or disperses in the saliva. Fast dissolving tablets are also called as mouth dissolving tablets, orodispersible tablets, rapi melts, porous tablets, quick dissolving etc.The faster the drug into solution, quicker the absorption and onset of clinical effects. Some drugs are absorbed from mouth, pharynx and esophagus as the saliva 47
  2. 2. ISSN: 2348 –0882 ========================================================================== Int. J. Pharm. Res. Sci., 2014, 02(1), 47-59. passes down into the stomach. In such cases bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. According to European pharmacopoeia, the ODT should disintegrate in less than three minutes. The basic approach in development of fast dissolving tablets is the use of the superdisintegrants like crosscarmellose sodium and sodium starch glycolate. Which provide instaneous disintegration of the tablets after putting on tounge, their by release the drug in saliva.The bioavailability of some drug may be increased due to absorption of drug in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into stomach (Madhusudan et al.,). 2. MATERIAL AND METHODS: 2.1 Material: Carbamazepine is obtained as a gift sample from Abbott pvt ltd, Mumbai. Croscarmellose sodium is obtained from Fine chem industry Mumbai. Sodium starch glycolate is obtained from Chemika Biochemika Reagents. All other chemicals used were of analytical grade. 2.2 Methods: 2.2.1 Preparation of solid dispersion of Carbamazepine Carbamazepine solid dispersions were prepared by solvent evaporation, melting and kneading methods using drug: polyethylene oxide N10 in proportion, viz. 1:1, 1:1.25, 1:1.5, 1:2. (Drug: Carrier). Methanol and isopropyl alcohol were selected as common solvents for solid dispersion. 2.2.1.1 Solvent evaporation method: The 100 mg of carbamazepine was dissolved in 20 ml of methanol in beaker and weighed amount of polyethylene oxide N 10 was added and stirred to dissolve both drug and carrier to get clear solution. Solution was poured on Petri plate and allowed to evaporate the solvent. The process of evaporation was operated until all methanols get evaporated. Solid dispersion prepared was then dried at room temperature and stored in desiccators for further study (Lewis et al., 2009). www.ijprsonline.com 2.2.1.2 Kneading method Accurate weighed amount of Carbamazepine and polyethylene oxide N 10 were taken into glass mortar and then methanol was added in small quantity to make paste. The paste was allowed to stand for 45 mins and then dried in oven at 400c. The product obtained was pulverized and passed through mesh (#) 80 and stored in desiccator for further study (Madhavi et al., 2011). 2.2.1.3 Physical mixture: Accurate weighed amount of Carbamazepine and polyethylene oxide N 10 were taken into glass mortar and then mixed for 10 minutes to get good mixture of drug and polymer. Then product was stored in the desiccator for further study (Kahkeshan et al., 2012). 2.2.1 Formulation of fast dissolving tablets: Fast dissolving tablets containing optimized solid dispersion were prepared by direct compression method using single punch tablet machine to produce convex faced tablets weighing 500 mg each with a diameter of 12 mm. A minimum of 40 tablets were prepared for each batch (Solanki et al.,2011). 2.2.2 By direct compression technique The direct compression technique was selected for developing novel fast dissolving tablets. In direct compression technique all materials accurately weighed like solid dispersion complex, microcrystalline cellulose, sodium saccharine, talc, magnesium state, and mannitol passed through a 40 mesh prior to mixing. The solid dispersion complex was properly mixed with superdisintegrant, and then with diluents MCC. The mixture was mixed with talc, sodium saccharine, magnesium state and mannitol. Then mixture was subjected to compression using single punch tablet machine (Solanki et al.,2011). 48
  3. 3. Table 1. Formulation of fast dissolving tablets using croscarmellose sodium Ingredients in (mg) SD complex Croscarmellose sodium Microcrystalline cellulose Mannitol Magnesium state Sodium saccharine talc Total weight F1 250 10 145 75 5 10 5 500 F2 250 20 135 75 5 10 5 500 F3 250 30 125 75 5 10 5 500 F4 250 40 115 75 5 10 5 500 F5 250 50 105 75 5 10 5 500 F6 250 75 80 75 5 10 5 500 Table 2. Formulation of fast dissolving tablets using sodium starch glycolate Ingredients in (mg) F1 F2 F3 SD complex 250 250 250 Sodium starch glycolate 10 20 30 Microcrystalline cellulose 145 135 125 Mannitol 75 75 75 Magnesium state 5 5 5 Sodium saccharine 10 10 10 talc 5 5 5 Total weight 500 500 500 resistant to powder flow. However, a high bulk 2.2.3 Characterization of blends: The quality of tablet, once formulated by rule, density does not necessarily imply a close-packed is generally dictated by the quality of low-porosity bed, as bulk density is directly physicochemical properties of blends. There are proportional to true density. Bulk density can be many formulations and process variables defined as the mass of powder divided by the bulk involved in mixing step and all these can affect volume. Bulk density of powder blends was the characteristics of blend produced. The determined using 25ml calibrated plastic characterization of mixed blend done for the measuring cylinder, in which powder blends were flow property of powder that are bulk density, simply poured and bulk density was measured in tapped density, Hausner’s ratio, Compressibility unit gm/ml. Bulk density is also known as fluff or index, angle of repose. The various poured bulk density. It can be calculated by characteristics of blends tested are given below following equation, and results were shown in Table below (Kakde et Bulk Density = Mass/volume al.,2010). ρb = M/Vb Bulk density Tapped density Bulk density of powder blend is always less than As stated above that due to interparticulate voids the true density of its component particles because bulk density of a powder is always less than true the powder contains interparticulate pores or density. This statement reveals that whereas as a voids. The bulk density of powder is dependent on powder can only possess a single true density, it particle packing and changes as powder can have many different bulk densities, depending consolidates. A consolidated powder is likely to on the way in which the particles are packed and have a greater arch strength than a less the bed porosity. For powders having comparable consolidated one and may therefore be more true densities, an increase in bulk density causes 49
  4. 4. decrease in porosity. This increases the number of interparticulate contacts and contacts areas and causes an increase in cohesion. In very coarse particles this may still be insufficient to overcome the gravitational influence on particles. Tapped density is defined as the mass of a powder divided by the tapped volume. Tapped density of powder blends was performed for 100 taps by using digital bulk density equipment and was measured in unit of gm/ml. True density is also known as equilibrium, tapped or consolidated bulk density. It can be calculated by following equation, Tapped Density = Mass/ Tapped volume ρt = M/Vt ’ Carr s Compressibility index The simplex way of measurement of the free flow of powder is compressibility, an indication of ease with which a material can be induced to flow is given by compressibility index of the granules was determined by Carr’s compressibility index (I) which is calculated by using the formula (Rockville et al.,2000). Compressibility index = Bulk volume – Tapped volume/Bulk volume × 100 Table 3. Compressibility Index as an Indication of Powder Flow Properties Carr̀,s Index (%) >12 12-16 18-21 23-35 33-38 >40 Type of Flow Excellent Good Fair to passable Poor Very poor Extremely poor funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of heap (r) was measured and angle of repose was calculated using formula -1 Ө = tan h/r Where, Ө is angle of repose, h is height of pile and r is radius of base pile. Hausner ratio Hausner ratio is an indirect index of ease of powder flow. It is calculated by the following formul Hausner ratio = tapped density/ bulk density Hausner ratio = ρt/ ρb Angle of repose Angle of repose was determined using fixed funnel method. The blend was poured through a Table 4. Angle of Repose as an Indication of Powder Flow Properties Angle of repose (o) <25 25-30 30-40 >40 2.2.2.4 Characterization of fast dissolving tablets: After compression of powder, the tablets were evaluated for diameter, thickness and physical characteristics like hardness, friability, Type of flow Excellent Good Passable Very poor disintegration time, wetting time, dispersion time and dissolution studies. The results were shown in Table below. Tablet Thickness 50
  5. 5. Ten tablets from each batch formulation were from each formulation and weighed collectively selected randomly and their thickness was and average weight was calculated using digital measured with a screw gauge for calculating balance. The individual weights were compared thickness variation (Shirsand et al.,2010). with the average weight for obtaining weight variation. Uniformity of weight As per IP twenty tablets were taken randomly Table 5. Weight Variation Limits for Tablets as per IP. Average of Tablets (mg) Maximum% difference allowed 130 or less 10 130-324 7.5 More than 324 5 The In vitro dispersion time of fast dissolving Hardness Hardness of the tablet was measured using the tablets of carbamazepine was determined by Monsanto hardness tester (soumya et al.,2013). placing one tablet in a beaker containing 100 ml of phosphate buffer and time required for Friability Friability of the tablets was determined using complete dispersion was determined. Roche friabilator. This device subjects the Wetting time tablets to the combined effect of abrasions and Wetting time of fast dissolving tablets of shock in a plastic chamber revolving at 25 rpm carbamazepine was determined by carefully and dropping the tablets at a height of 6 inch in placing tablets on to a twice folded circular tissue each revolution. Pre-weighed sample of tablets paper placed in a Petri-dish having the internal was placed in the friabilator and were subjected diameter of 5 cm containing 6 ml of water. The to 100 revolutions. Tablets were dusted using a time required for water to reach the upper surface soft muslin cloth and reweighed. The friability of the tablet and to completely weight the tablet (F %) is determined by the formula (Rangole et was noted as wetting time(Rangole et al.,2008). al., 2008). Water absorption ratio % friability = loss in weight/initial The weight of the tablets prior to placing in Petri weight×100 dish was noted (wb) using the digital balance. The weighted tablet was removed and reweighed (wa). Water absorption ratio(R) was then determined Drug content uniformity Drug content of fast dissolving tablets of according to the following equation. carbamazepine was calculated by weighing ten R = 100× (wa-wb) tablets of each formulation, pulverizing to a fine Where, wb and wa were tablet weights before and powder. A quantity of powder equivalent to 10 mg after water absorption respectively. of carbamazepine dissolved in methanol and In-vitro dissolution study solution was filtered through a 0.45 μm whatmann In-vitro dissolution study of fast dissolving tablets filter paper. Carbamazepine content was of carbamazepine was performed according to determined by measuring the absorbance at 285 USP type-II dissolution apparatus employing a nm at UV visible spectrophotometer after paddle stirrer at 50 rpm using 900 ml of phosphate appropriate dilution with methanol. The drug buffer of pH 6.8 at 37±0.5 as dissolution medium. content was determined using calibration curve. One tablet was used in each test. Aliquots of the The mean percent drug content was calculated as dissolution medium 5 ml were withdrawn at an average of three dimensions(Masareddy et specific time interval 5, 10, 15,20,25,30 minutes al.,2008). and replaced with the equal volume of fresh medium. The samples were filtered through 0.45 μm whatman analyzed by measuring the In Vitro dispersion time 51
  6. 6. absorbance at 285 nm. Drug concentration was IR Spectrum of Carbamazepine calculated from the standard calibration curve and IR spectrophotometer was used for infrared expressed as cumulative percent drug dissolved. spectroscopy analysis of carbamazepine. The The release studies were performed in triplicate samples were prepared in KBr disk by means of a (Arora et al.,2010). hydrostatic press. The scanning range was 4004000 cm-1 (Wan et al., 2012). In-vitro Disintegration time Disintegration of FDT was generally occurring DSC of Carbamazepine due to water uptake by superdisintegrant via Differential scanning calorimetry (DSC) capillary action, which results in swelling of measurements were performed on SDT Q600 superdisintegrants and tablet get disintegrated. It Differential scanning calorimeter. The accurately was also reported that increased compaction force weighed sample was placed in an aluminium pan may increase or decrease disintegration time. In and an empty aluminium pan was used as a the present study disintegration test was carried reference (Wan et al.,2012). out on six tablets using the apparatus specified in XRD of carbamazepine USP (Electrolab disintegration apparatus USP). XRD of carbamazepine was carried out by using 0 0 The distilled water at 37 C ± 2 C was used as a the Philips PW 1729 X-ray generator (Wan et disintegration media and time in second taken for al.,2012). complete disintegration of the tablet with no 3. RESULT AND DISSCUSION: palpable mass remaining in the apparatus was measured in seconds (Pandit et al., 2012). Table.6. Solubility of PM and SD in water: Drug: Polymer ratio Solubility (mg/ml) PM SE KM 1:1 0.13 0.16 0.27 1:1.25 0.14 0.18 0.29 1:1.5 0.15 0.19 0.35 1:2 0.14 0.17 0.26 From table 6 it is know that Solubility of evaporation and kneading method. Kneading carbamazepine is increased by different methods method is only method which gives the high of solid dispersion like physical mixture, solvent solubility than other method i.e. 0.35 mg/ml. Table.7.Solubility data of SD prepared by KM in water: Drug: Polymer ratio Solubility (mg/ml) 1:1 0.27 1:1.25 0.29 1:1.5 0.35 1:1.75 0.29 1:2 0.26 1:3 0.23 1:4 0.23 From table 7 it is clear that proportion of drug to polymer ratio 1:1.5 give the high solubility i.e. 0.35 mg/ml that’s why 1:1.5 proportion is used for preparing fast dissolving tablets which gives high drug release with in 30 mins i.e. 87.5±1.5. 3.1Drug polymer interaction studies: Drug and polymer interaction study was carried out by doing the different analysis of pure 52
  7. 7. carbamazepine, physical mixture, solid dispersion, Fourier Transform Infrared Spectroscopy polymer and the formulation. Figure 1. IR spectra of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) Solid almost the same wave number with same intensity Dispersion E) Formulation F. IR spectrum of pure carbamazepine, in the spectra of physical mixture solid dispersion polyox N 10, Physical Mixture and Solid which indicate that the absence of any potential dispersion are shown in figure 1. The IR spectra physical or chemical interaction between drug and of pure carbamazepine showed peak at 3458.37, polymer and other additives, Hence drug nad 3153.61, 3032.10, 1666.50, 1595.13, 1477.47, polymer were found to be compatible with the -1 1377.17 cm indicating stretching of N-H, C-H, drug. C-H aromatic, amide, C-N , N-H deformation respectively. These peaks seemed to be retained at Differential Scanning Colorimetry Analysis 53
  8. 8. Figure 2. DSC thermogram of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) Solid Dispersion E) Formulation F5 One of the most classic application of DSC physical mixture, solid dispersion and formulation analysis is the determination of the possible F5.Endothermic peak of caarbamazepine was not interaction between the drug and excipients in the observed in Physical mixture, solid dispersion and formulation supporting evidence for compatible formulation F 5 because carbamazepine is between drug and excipients was obtained from dispersed in the polyox N10 at molecular level. DSC analysis studies. As shown in the figure 2 the This indicate the absence of any DSC thermogram of carbamazepine showed sharp interaction between drug and excipients, Hence 0 endothermic peak at 193.93 c which is near to from above DSC thermogram, it was found that melting point of carbamazepine.DSC thermogram there was compatibility between drug and 0 of polyox N 10 showed sharp melting at 73.44 c excipients. which also observed in DSC thermogram of X- Ray Diffraction (XRD) XRD pattern were recorded using Philips 1729 X-ray generator. Powder X-ray diffraction patterns were recorded for drug, physical Mixture, solid dispersion and polymer. Figure 3 . XRD pattern of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) Solid Dispersion Figure 3 shows the diffraction pattern of peaks were observed at 2θ values of 10.32, 13.32, pure carbamazepine which shows its crystalline 16.16, 19.76, 25.14, 27.88, and 32.33 in nature that was demonstrated by numerous sharp, fingerprint regions referring to its crystallinity. highly intense and less diffused peaks. These 54
  9. 9. Peak height of pure carbamazepine was selected to calculate the RDC of CBZ, best physical mixture and solid dispersion. When pure CBZ was considered as a reference sample, a significant decrement in crystallinity of the characterized solid dispersion was observed (˂ 0.1).RDC values were 1, 0.9 and 0.6. For pure drug, physical mixture and solid dispersion respectively indicating the amorphousness of drug, polymer. 3.2 Characterization of blend for fast dissolving tablets: The data for evaluation of powder blends of rapidly disintegrating tablets of carbamazepine is as shown below. Table 7. Characterization of blends: Formulation code Bulk density Tapped density Hausner’s̀́ ratio Carr’s index Angle of repose (gm/cm3) (gm/cm3) (%) (Ө) 0.33±0.007 0.37±0.01 1.14±0.008 12.68±0.01 29.7±0.43 F1 0.33±0.01 0.40±0.012 1.20±0.005 16.62±0.69 29.57±0.33 F2 0.31±0.01 0.36±0.010 1.12±0.005 12.93±0.34 26.33±0.39 F3 0.31±0.01 0.39±0.013 1.17±0.008 17.30±0.21 25.38±0.25 F4 0.32±0.01 0.37±0.016 1.12±0.008 11.62±0.25 24.29±0.05 F5 0.33±0.01 0.40±0.007 1.16±0.005 13.27±0.38 28.38±0.21 F6 0.34±0.01 0.40±0.008 1.17±0.008 14.22±0.34 27.46±0.57 F7 0.30±0.01 0.34±0.008 1±0.007 12.39±0.26 25.19±0.10 F8 0.29±0.01 0.35±0.01 1.18±0.03 17.57±0.27 27.45±0.17 F9 Bulk density of powder blends of different formulation was found to be in the range of 0.29 to 0.34 gm/cm3 whereas the tapped density was found to be in the range of 0.35 to 0.40 gm/cm3. Angle of repose was found to be less than 300 which indicate good flow characteristics of the powder blends. Carr’s index was found to be in the range of 11.62 to 17.57 whereas the Hausner ratio was found to be less than 1.25. Both this values indicate good flow property and good compression characteristics. 3.3 Evaluation of fast dissolving tablets 3.3.1 Evaluation of physical parameter of tablets The data for evaluation of physical parameters of fast dissolving tablets of carbamazepine is as shown below. 55
  10. 10. Table 8. Evaluation of fast dissolving tablets. Formulation code Weight variation (mg) Passes F1 Passes F2 Passes F3 Passes F4 Passes F5 Passes F6 Passes F7 Passes F8 Passes F9 Diameter (mm) 12.00±0.007 12.02±0.007 12.024±0.005 12.024±0.005 12.036±0.011 12.054±0.018 12.054±0.015 12.042±0.017 12.064±0.023 Thickness Hardness Friability (mm) (Kg/cm2) (%) 4.326±0.019 3.14±0.054 0.65±0.11 4.4±0.035 3.22±0.10 0.63±0.11 4.368±0.024 3.04±0.11 0.54±0.14 4.472±0.035 3.02±0.10 0.59±0.07 4.362±0.019 3.1±0.1 0.63±0.06 4.338±0.039 3.24±0.26 0.74±0.07 4.342±0.04 3.04±0.11 0.62±0.08 4.342±0.052 2.94±0.15 0.72±0.10 4.332±0.016 3.12±0.17 0.59±0.09 During weight variation test none of the tablet was while thickness was found to be in the range of found to be deviate by permissible percentage as 4.32 to 4.4 mm. Percentage friability was found to per Indian pharmacopoeia 5% from the mean be in the range of 0.49 to 0.74 which is within value of 20 tablets. Thus it was found that all the limit <1%. formulations complied with weight variation test. Hardness of the tablet was found to be in the 3.3.2 Wetting time and water absorption ratio range of 2.94 to 3.24, which was found to well The data for wetting time and water within the required hardness for the fast dissolving absorption ratio of fast dissolving tablets of 2 tablets (3 to 4 kg/cm ). Diameter of the tablets carbamazepine is as shown below. was found to be in the range of 12 to 12.064 mm Table 9. Data for wetting time and water absorption ratio. Formulation code Wetting time Water absorption ratio (sec) (%) F1 130.2±0.44 71.14±0.53 F2 116.4±0.89 72.50±0.47 F3 105.2±0.83 77.14±0.03 F4 106.2±0.83 83.35±0.68 F5 97±0.70 97.03±0.01 F6 101±0.70 87.34±0.38 F7 110.6±0.89 82.38±0.66 F8 102.8±0.44 86.26±0.39 F9 113.4±0.89 75.73±0.10 Wetting time was found to be in the range of 97.00 to 130.2. Water absorption ratio was found to be in the range of 71.14 to 97.03. It may be due to the hydrophilic nature of carriers used. This thing might result into increased capillary action which has resulted into decreasing the wetting time and increasing the water absorption ratio. 3.3.3 Disintegration time, uniformity of content and Disintegration time: The data for disintegration time, uniformity of content and Disintegration time of fast dissolving tablets of carbamazepine is as shown below. 56
  11. 11. Table 10. Data for disintegration time, drug content and Disintegration time of fast dissolving tablets of carbamazepine. Formulation code Disintegration time Drug content Dispersion (sec) (%) time (Sec) F1 85.33±1.52 95.43±0.91 91.10±0.7 F2 80±1.0 98.23±0.96 83.20±1.20 F3 76±1.0 101.84±1.11 81.46±0.5 F4 65±2.0 99.88±0.511 71±1.5 F5 57±1.0 98.85±1.04 62.20±0.6 F6 61.66±1.52 98.39±1.20 67.16±1.2 F7 71.66±1.52 96.22±0.80 75.87±1.4 F8 61±1.0 98.46±0.61 65.57±0.4 F9 63±1.0 102.08±1.09 64±0.5 3.3.4 Disintegration time: In vitro disintegration times of all formulations were found to be in the range of 57 to 85.33 Sec, this was found to be well within the acceptable limit for fast dissolving tablet (≤ 3 min). In vitro disintegration time of all the formulations was found to decrease with correspondent increase in the concentration of both croscarmellose sodium and sodium starch glycolate. It may be due to the hydrophilic nature of sodium starch glycolate and croscarmellose sodium which attracts water and may increase the capillary action of the tablet matrices which result into decreasing the disintegration time. 3.3.5 Uniformity of content: All the formulations upon spectroscopic analysis were found to contain carbamazepine in the range of 95.43 to 102.08 which complies with the standard for uniformity of content laid down for carbamazepine in official compendia. 3.3.6 In vitro Dispersion time: In vitro dispersion time of all formulation was found to be in range of 62.20 to 91.10 sec, this was found to be well within acceptable range. 3.3.7 In vitro Dissolution study: During in vitro dissolution study, it is found that within 30 minutes drug release was found to be 62% to 83% from F1 to F9 formulation. The F5 formulation which contain 10% of the croscarmellose sodium which shows 83.6% of drug release. It was also observed that as the concentration of the croscarmellose increases drug release increases upto 10% and then get decreased. In case of the sodium starch glycolate concentration used were 2, 4 and 6%. From that 4% concentration of SSG shows 80.2% and other shows less. This may also attribute to croscarmellose sodium and sodium starch glycolate. With increase in concentration of this polymer capillary action might have increased which in turn resulted in reducing the time required for wetting and disintegration of tablets and finally the dissolution of drug. 57
  12. 12. Table 11. In vitro dissolution profile of formulationF1- F9. Time (min) Cumulative drug release (%) F1 F2 F3 F4 F5 F6 F7 F8 F9 0 0 0 0 0 0 0 0 0 0 5 10 15 20 25 30 20.3±1.5 24.7±2.5 32.5±2.1 40.1±1.2 51.2±1.2 62.7±2.0 24.0±1.5 29.5±0.7 35.7±1.0 47.5±1.8 59.4±2.8 66.5±2.5 27.2±2.4 33.5±1.4 39.3±2.4 49.2±2.4 62.4±0.7 70.2±1.4 38.0±1.2 41.1±3.2 46.5±2.2 57.1±1.6 65.6±2.3 78.5±2.7 40.2±2.3 47.3±2.2 52.0±1.5 59.7±0.4 69.4±1.4 83.6±2.3 29.2±1.1 34.9±0.9 41.5±1.4 50.8±1.8 65.9±1.4 71.2±2.0 29.2±1.1 34.9±0.9 40.3±0.7 51.3±1.2 61.3±2.0 70.2±1.1 39.5±1.8 40.0±2.5 48.8±1.2 57.8±0.4 67.8±2.0 80.2±0.6 25.4±1.6 31.4±0.8 38.4±1.4 54.9±1.3 59.3±3.3 70.7±1.3 90 Cumulative % drug release 80 70 F1 60 F2 F3 50 F4 40 F5 30 F6 20 F7 10 F8 0 0 5 10 15 20 25 30 35 F9 Time (min) Figure 4. In vitro dissolution profile of formulationF1- F9. Conclusion: The oral fast dissolving tablet of carbamazepine were formulated and evaluated for various parameters from the compatibility studies by DSC, FTIR and XRD of drug it was found to be compatible with other formulation excipients. All evaluation parameter were within specification. The release of drug from the tablet was increased as the concentration of superdisintegrants was increased. The croscarmellose sodium shown faster drug release than sodium starch glycolate. Formulation F5 release maximum drug within the 30 mins.i.e.83.6% and shown minimum disintegration time i.e. 57 sec than other formulation and hence considered best formulation. It is concluded that fast dissolving tablets of carbamazepine could be prepared by using croscarmellose sodium and sodium starch glycolate. In which croscarmellose sodium shows good result as compared to the sodium starch glycolate. Acknowledgement: We wish to thank Abbott healthcare Pvt.Ltd for providing carbamazepine as a gift sample. We also wish to thank Yashoda technical campus Satara for providing instruments and facilities required for research work. 58
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