Formulation and Evaluation of Candesartan Cilexetil Mouth Dissolving Tablet by using Natural Superdisintegrant
S. M. Ragade1*, M. M. Bari2, S. D. Barhate2
1Ambedkar Nagar, Bhusawal, Dist- Jalgaon, Maharashtra, India. 425201
2Shri Sureshdada Jain Institute of Pharmaceutical Education and Research, Jamner, Dist- Jalgaon, Maharashtra, India.
*Corresponding Author E-mail: ragadesapna0206@gmail.com
ABSTRACT:
The objective was to isolate natural superdisintegrants and prepare mouth dissolving tablet of candesartan cilexetil using that isolated natural superdisintegrants, as an alternative for the synthetic superdisintegrant. Also the comparision of natural superdisintegrants on D.T and drug release. Isapghulla seeds and fenugreek seeds mucilages were isolated manually by extraction. The isolated mucilages were dried and used in the formulation of candesartan cilexetil MDT by direct compression method. Organoleptic, phytochemical and physicochemical parameters of mucilages were performed. Precompression and post compression parameters were performed and batch CCMP4 showed that all the parameters were evaluated satisfactorily. In vitro dissolution of candesartan cilexetil MDT of CCMP4 was found to be, 98.16% within 15 minutes and D.T 8 seconds. As compared to CCMF3 was found to be, 81.90% within 20 minutes, and D.T 26 seconds. It was concluded that candesartan cilexetil mouth dissolving tablets were prepared successfully by using isapghulla seeds and fenugreek seeds dried mucilages, which are the alternative to the synthetic superdisintegrants. It was also concluded that isapghulla seeds dried mucilage as natural superdisintegrant, rapid disintegration time and good drug release, than fenugreek seeds dreid mucilage.
KEYWORDS: Isapghulla fenugreek seeds dried mucilages, natural, synthetic superdisintegrants, mouth dissolving tablet, candesartan cilexetil.
INTRODUCTION:
To obviate the problems associated with conventional dosage forms, mouth dissolving tablets have been developed having good hardness, dose uniformity, easy administration and serves as the first choice of dosage form for paediatrics, geriatrics and travelling patients.
They are convenient to be manufactured & administered, free of side effects, offering onset of release & enhance bioavailability, so as to achieve better patient compliance.[1] Center for Drug Evaluation and Research and FDA states MDT to be: “A solid dosage form containing medicinal substances, which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue”.[2,3] Disintegrating agent plays very much important role in the disintegration of tablet. They are of two types synthetic as well as natural.
Mucilage is most commonly used as adjuvant in the manufacturing of different pharmaceutical dosage forms. Mucilages are generally polysaccharides, which are polymeric in nature and are obtained from woody and non-woody plant parts such as bark, seeds, sap, roots, rhizomes, fruits, and leaves. They possess a variety of pharmaceutical properties, which include binding, disintegrating, suspending, emulsifying and sustaining properties at different proportion in different pharmaceutical dosage forms. Natural mucilages are preferred over semi-synthetic and synthetic materials due to their non-toxic, low cost, free availability, emollient and non-irritating nature.[4] Ispaghula mucilage consists of epidermis of the dried seeds of Plantago ovate and fenugreek seeds are obtained from Trigonella foenum graecum L., an herbaceous plant of leguminaceae or fabaceae family.[5] The present work was carried out to study the disintegrant property of Plantago ovata mucilage and fenugreek seeds mucilage in comparison with each other by formulating mouth dissolving tablets of candesartan cilexetil.
Candesartan cilexetil is a type of medicine called an angiotensin II receptor inhibitor (or antagonist), a non-peptide, is chemically described as (±)-1-Hydroxyethyl 2-ethoxy-1-[p-(o-1H-tetrazol-5ylphenyl) benzyl] -7-benzimidazolecarboxylate,cyclohexylcarbonate(ester).
Candesartan cilexetil is a white to off-white powder with a molecular weight of 610.67. It is practically insoluble in water and sparingly soluble in methanol. Its empirical formula is C33H34N6O6 [6,7] and its structural formula is as follows:[8]
Structure of candesartan cilexetil
Adverse effects: Hypertension, oliguria, progressive azotemia, or acute renal failure.
Candesartan is an angiotensin II receptor antagonist which is used in the management of hypertension and may also be used in heart failure in patient with impaired left ventricular systolic function. May be used as a first line agent to progression of diabetic nephropathy. Onset of antihypertensive effect occurs about 2 hrs after administration and maximum effect is achieved within about 4 weeks after initiating therapy.[3] In hypertension initial dose of candesartan is 8 mg or 16 mg once daily. The usual maintenance dose is 8 mg once daily, but doses up to 32 mg daily, as single or in 2 divided doses. In heart failure, candesartan is given as initial dose of 4 mg once daily. The dose should be doubled at interval of not less than two weeks up to 32 mg once daily if tolerated.
MATERIALS AND METHOD:
MATERIALS:
Candesartan cilexetil, Avicel PH102, Pearlitol SD200, Aspartame, Plantago ovata dried mucilage, Fenugreek seeds dried mucilage, pipermint flavour, Magnesium stearate, Talc and Aerosil etc.
METHODS:
1. Method for Isolation of mucilages:[9]
A. Isolation of Isapghulla Seeds Mucilage (Plantago ovata seeds mucilage):
Imported psyllium seeds were mixed with 10 to 30 times their weight of water and allowed to stand for 10 to 30 hours. The solution was the pressed through cloth and the mucilage were obtained by addition of three volumes of 95 per cent ethanol. In other cases the mucilage were isolated by extracting the seed for hour with hot water. The yield of mucilage obtained by thorough extraction approximately 20 per cent of the weight of the seeds used, and then it was dried in hot air oven or by using vaccum oven at 400C. The dried mucilage was ground by a mechanical grinder and passed through # 60 mesh sieve and kept in a desiccator.
B. Isolation of Fenugreek Seeds Mucilage:
The seeds were washed with double distilled water to remove any adherent material. The seeds were pulverized and about three times its volume of water was added and kept aside with occasional stirring using mechanical stirrer. The process continued for about 5 hours until the slurry was prepared. The viscous solution was then filtered through eight fold muslin cloth. The process was repeated 4 times with the residue on the muslin cloth. All the filtrate was added together. Then the filtrate was precipitated in about three times its volume of ethanol with mechanical stirrer. The precipitate was washed for three times with ethanol and dried at 40°C. The dried mucilage was ground by a mechanical grinder and passed through # 60 mesh sieve and kept in a desiccator.
2. Characterisation of Mucilage [10,11]:
A. Physical Characterisation:
Organoleptic Evaluation:
The organoleptic evaluation refers to the evaluation of color, odor, shape, taste and special features which include touch and texture. The majority of information on the identity, purity and quality of the material can be drawn from these observations.
A. Phytochemical Characterisation:
Determination of Mucilage Purity:
To determine the purity of mucilage tests for alkaloids, carbohydrates, flavonoids, steroids, saponins, tannins and phenols were carried out.
C. Physicochemical Characterisation:
1. Swelling Index :
Swelling index of mucilage was determined by using reported method. One gram of powder (#100 mesh) was accurately weighed and transferred to a 100 ml stopper measuring cylinder. The initial volume of the powder in the measuring cylinder was noted. The volume was made up to 100 ml with distilled water. The cylinder was stoppered, shaken gently and set aside for 24 hours. The volume occupied by the gum sediment was noted after 24 hours. Swelling index (SI) is expressed as a percentage and calculated according to the following equation.
% SI= Final volume – Initial volume Initial volume
2. Solubility:
Solubility of powder was checked in different solvents such as water, hot water, ethanol, methanol, ether, acetone, chloroform etc.
3. Moisture Absorption:
The dried mucilage powder was accurately weighed and kept in a desiccator. After 3 days, the sample was taken out and weighed. The percentage of moisture uptake was calculated as the difference between final weight and initial weight with respect to initial weight.
4. Loss on Drying (LOD):
Moisture content of mucilage was determined by loss on drying method. Accurately weighed 1 g mucilage sample was heated at 105°C to get a constant weight in a hot air oven and percent loss of moisture on drying was calculated using following formula,
% LOD = Weight of moisture in sample Weight of sample before drying × 100
5. pH of Mucilage:
The pH of 1% w/v dispersion of the mucilage was determined using a digital pH meter.
3. Preformulation studies:
1 Estimation of candesartan cilexetil [12.13]
A solution of candesartan cilexetil was prepared in phosphate buffer pH 6.8 and recorded UV spectrum using UV/VIS Spectrophotometer.
Procedure:
Preparation of standard solution:
· 100 mg of candesartan cilexetil was accurately weighed and added into 100 ml volumetric flask and dissolve in small quantity of methanol, and the volume was made up with the phosphate buffer pH 6.8 to get the concentration of 1000mg/ml. From this 1 ml was withdrawn and diluted to 100 ml to get concentration of of 100mg/ml.
· From that aliquots of 0.5, 1, 1.5, 2, 2.5, 3ml were pippeted out into 10ml volumetric flasks. The volume was made up with phosphate buffer pH 6.8 to get the final concentrations of 5, 10, 15, 20, 25, 30 mg/ml respectively. The absorbance of each concentration was measured at 254 nm.
· UV Spectrophotometer:
The UV spectrum of candesartan cilexetil solution in pH 6.8 buffer was scanned at 400 nm to 200 nm. Shows Lamda max of candesartan cilexetil.
2 Diffrential Scanning Calorimetry Study:
DSC analysis of pure drug was performed with Shimadzu DSC 60 thermal analyser at the heating flow rates of 100 c per min between 10 and 3000 c under static air using aluminium pans. The thermo gram was shown in the fig. 4 and 5 respectively.
3. Drug Polymer Compatability Studies:
The drug, polymer and physical mixtures were subjected to fourier transform infrared studies by ATIR technique to check drug polymer interaction, using Aglient Cary 630 FTIR spectrophotometer. Fitted with kBr optics and complimentary diamond ATIR accessory which is having the spectral range 400 - 200 cm-1. The infrared spectra of candesartan cilexetil, plantago ovata seeds dried mucilage, fenugreek seeds dried mucilage and polymer + drug, were shown in fig. 6,7,8,9,10 respectively. Then these spectrum were compared.
Pre compression parameter[14.15]
4. Bulk density:
Loose bulk density and tapped density were determined. A quantity of 10 gm of powder from each formula, previously lightly shaken to break any agglomerates formed, was introduced into a 10 ml measuring cylinder. After the initial volume was observed, and the allowed cylinder allowed to fall on its own weight onto a hard surface from the height of 2.5 cm at 2 second intervals. The tapping was continued until no further change in volume was noted. BD and TD were calculated using the following formula,
BD = Mass/ volume
TD = Mass/ Tapped volume
5. Hausner’s ratio:
Hausner’s ratio gives an idea regarding the flow of the blend. It is the ratio of tapped density to the bulk density. Hausner’s ratio is calculated as:
Tapped density
Hausner’s Ratio = ----------------------
Bulk density
6. Compressibility Index:
The compressibility index measures the propensity of powder to be compressed. The packing ability of drug was evaluated from change in volume, which is due to rearrangement of packing occurring during tapping. It is indicated as Carr’s index (CI) and can be calculated as follow,
Tapped density –Bulk density
% CI = ------------------------------------- X 100
Bulk density
7. Angle of Repose:
A funnel was held with a clamp such that the stem of the funnel is 2 cm above the graph paper is Weighed amount of blend 5 gm was taken and poured into the funnel keeping the orifice of funnel blocked. The powder was allowed to flow by removing the blockage until the apex of the conical pile just touches the tip of the funnel. Height of pile and average of six diameters formed by the pile of the powder was measured with the help of a ruler and the angle of repose was determined.
θ = tan-1 (h/r)
Where;
h - Height of powder pile
r - Radius of powder pile
θ - Angle of repose
4. Formulation [9.16]:
Table 1: Formulation of candesartan cilexetil mouth dissolving tablet by direct compression method
S/N |
Ingredients |
Batches |
|||||||
CCMP |
CCMF |
||||||||
|
|
1 |
2 |
3 |
4 |
1 |
2 |
3 |
4 |
1 |
Candesartan cilexetil |
16 |
16 |
16 |
16 |
16 |
16 |
16 |
16 |
2 |
Pearlitol SD200 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
3 |
Avicel PH102 |
116.25 |
113.75 |
111.25 |
108.75 |
116.25 |
113.75 |
111.25 |
108.75 |
4 |
Aspartame |
7.5 |
7.5 |
7.5 |
7.5 |
7.5 |
7.5 |
7.5 |
7.5 |
5 |
PO mucilage dried powder |
5 |
7.5 |
10 |
12.5 |
- |
- |
- |
- |
6 |
Fenugreek mucilage dried powder |
- |
- |
- |
- |
5 |
7.5 |
10 |
12.5 |
7 |
Pippermint flavour |
0.250 |
0.250 |
0.250 |
0.250 |
0.250 |
0.250 |
0.250 |
0.250 |
8 |
Magnesium stearate |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
9 |
Talc |
2.5 |
2.5 |
2.5 |
2.5 |
2.5 |
2.5 |
2.5 |
2.5 |
10 |
Aerosil |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
|
Average Weight |
250 |
250 |
250 |
250 |
250 |
250 |
250 |
250 |
*All values are in mg
Procedure:
1. Weigh all the ingredients accurately.
2. The candesartan cilexetil was sifted through sieve #60, All the other ingredients, Avicel PH102, pearlitol SD200, aspartame, plantago ovata dried mucilage, fenugreek seeds dried mucilage, were sifted through # 60 and mixed in a polybag for 5 min manually.
3. That were then lubricated by adding magnesium stearate, talc and aerosil for 2 minutes.
4. The lubricated granules were evaluated for precompression parameters.
5. This were compressed on 12 station multi tooling CIP Lab press compression machine using 9mm s/c punch.
6. Compressed tablets were evaluated for post compression parameters.
5. Post compression parameter [15.17]
1. Weight Variation:
Twenty tablets were randomly selected from each formulation and weighed individually to check for weight variation. The following percentage deviation in weight variation according to IP was allowed.
2. Thickness:
Twenty tablets were randomly selected and thickness was measured individually. It was expressed in millimetre.
3. Hardness:
Hardness indicates the ability of tablet to withstand mechanical shocks while handeling. The hardness of the tablets was measured using Monsanto hardness tester, It was expressed in (kg/cm2).
4. Friability:
The friability of tablets were determined using Roche friabilator. Tablets were transferred in the friabilator. The friabilator was operated at 25 rpm for 4 minutes. The tablets were dedusted and weighed again. The percentage friability was calculated by,
Winitial–Wfinal
% F= ------------------------ X 100
Wfinal
% Friability of tablets less than 1% is acceptable.
5. Disintegration time:
The test was carried out on 6 tablets using the disintegration test apparatus. Distilled water at 37ºC ± 2ºC was used as a disintegration media and the time in second taken for complete disintegration of the tablet with no palatable mass remaining in the apparatus was measured in seconds.
6. Uniformity of Dispersion:
Two randomly selected tablets were kept in 100 ml water and stirred for two minutes. The dispersion was passed through 22 mesh. The tablets were considered to pass the test if no residue remains on the screen.
7. Wetting time:
A piece of tissue paper (12cmx10.75cm) a petri dish (Internal diameter = 9cm) containing 9ml of buffer solution pH 6.8. 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 noted.
8. Water absorption ratio (%)
A piece of tissue paper folded twice was placed in a small petri dish containing 6 ml of water.
A tablet was put on the paper & the time required for complete wetting was measured. The
wetted tablet was then weighed. Water absorption ratio, R, was determined using following
equation,
R=10 (Wa/Wb)
Where,
Wb - Weight of tablet before water absorption
Wa - Weight of tablet after water
9. Drug content uniformity:[8]
To 1 tablet of candesartan cilexetil add 30 mL of a mixture of acetonitrile and water (3:2), shake vigorously for 20 minutes, then add a mixture of acetonitrile and water (3:2) to make exactly volume so that each mL contains about 40 mg of candesartan cilexetil, centrifuge, and use the supernatant liquid as the sample solution. Separately, weigh accurately about 50 mg of candesartan cilexetil for assay, and dissolve in aceto-nitrile to make exactly 50 ml. Pipete 4 mL of this solution, add a mixture of acetonitrile and water (3:2) to make exactly 100 mL, and use this solution as the standard solution. Determine the absorbance, AT and AS, of the sample solution and standard solution under ultraviolet-visible spectrophotometry.
10. In-vitro dissolution study [8]
Dissolution parameters:
Instrument Tablet Dissolution Tester
Apparatus USP Type II, Paddle type
Make Electolab TDT 0.8L
Volume 900ml
Dissolution medium 0.35% of polysorbate 20, in 0.05M phosphate buffer pH 6.5.
RPM 50
Sampling 5, 10, 15, 20, 25, and 30 minutes.
Lamda max 254nm
Temperature 37±0.50 C
Result and Discussion
1. Isolation of mucilages
Plantago ovata mucilage and fenugreek mucilage were isolated from their seeds respectively, to be used as natural superdisintegrant in the formulation of candesartan cilexetil mouth dissolving tablet.
2. Characterisation of Mucilage
A. Organoleptic Properties
Result of organoleptic characterisation of plantago ovata and fenugreek mucilage were given in table 2.
B. Phytochemical parameters
Result of organoleptic characterisation of plantago ovata and fenugreek mucilage were given in table 3.
C. Physicochemical parameters
Result of physicochemical characterisation of plantago ovata and fenugreek mucilage were given in table 4.
3. Preformulation Studies:
1. Estimation of Candesartan Cilexetil:
Candesartan cilexetil solution was scanned at 400 nm to 200 nm, the maxima were observed at 254 nm shown in fig. 2. This was confirmed with standard UV spectrum of candesartan cilexetil.
2. Diffrential Scanning Calorimetry Study:
DSC study for pure drug was carried out. The thermo gram is shown in the fig. 4 and 5, it indicates that the melting of drug has started at and ended at 163.320C. It is matching with the standard value 1630C.
3. Drug Polymer Compatability Studies (FTIR):
From fig.6, 9, 10 it was cleared that, characteristic peak in the IR spectra of candesartan cilexetil with both the polymers were at same wave number as candesartan alone. Thus it reveals that candesartan cilexetil was compatible with plantago ovata as well as fenugreek dried mucilage.
4. Pre Compression Parameters:
The preformulation parameters such as bulk density, tapped density, carr’s index, hausner’s ratio and angle of repose were studied and found to be within limits, and data for the same given in the table 5.
5. Formulation Development:
Eight batches of the mouth dissolving tablets of candesartan cilexetil were prepared using plantago ovata dried mucilage and fenugreek dried seed mucilage as superdisintegrants by direct compression method.
6. Post Compression Parameters:
The tablets were evaluated for post compression parameters like, weight variation, thikness, hardness, friability, disintegration time, % drug content, wetting time and in vitro dispersion time. The related data were given in table 6 and 7.
7. In Vitro Dissolution Study:
Percentage release of candesartan cilexetil were given in table 8. Batch CCMP4 gives faster dissolution 98.16%, within 10 minutes. CCMF3 fenugreek mucilage as superdisintegrant shows highest dissolution 81.90%, within 20 minutes. Hence, CCMP4 was actively said to be good batch.Comparision between dissolution profile of all batches were shown in fig.10 and 11 resp.
Table 2: Result of Organoleptic Characterisation of Plantago Ovata Seeds and Fenugreek Seeds Mucilages,
Sr.No. |
Property |
Plantago ovata seeds mucilage |
Fenugreek seeds mucilage |
1 |
Color |
Light brown |
Off-white to light brown |
2 |
Odor |
Odorless |
Odourless |
3 |
Taste |
Tasteless |
Mucilaginous |
4 |
State |
Amorphous |
Amorphous |
5 |
Shape |
Irregular |
Irregular |
Table 3: Result of Physicochemical Characterisation of Plantago Ovata Seeds and Fenugreek Seeds Mucilages,
Sr.No. |
Test |
Observation |
|
Plantago ovata seeds mucilage |
Fenugreek seeds mucilage |
||
1 |
Ruthenium test |
Test present |
Test present |
2 |
Molish test |
Test present |
Test present |
3 |
Iodine test |
Test absent |
Test absent |
4 |
Enzyme test |
Test absent |
Test absent |
5 |
Test for steroids |
Test absent |
Test absent |
6 |
Test for saponins |
Test absent |
Test absent |
7 |
Test for tannins |
Test absent |
Test absent |
8 |
Test for alkaloids |
Test absent |
Test absent |
Table 4: Result of Physicochemical Characterisation of Plantago Ovata Seeds and Fenugreek Seeds Mucilages,
Sr.No. |
Parameter |
Observation |
|
Plantago ovate seeds mucilage |
Fenugreek seeds mucilage |
||
1 |
Swelling Index |
60±1.52 |
65±2.01 |
2 |
Solubility-Soluble Solubility-Insoluble |
Cold water Ethanol, methanol, acetone. |
Water Ethanol, acetone, chloroform |
3 |
Moisture absorption |
210±0.784% |
196±0.521% |
4 |
Loss on drying |
1.61±0.3606 |
4.18±0.25% |
5 |
pH |
6.6±0.34% |
6.9±0.30% |
Figure 2: Standard Calibration Curve of Candesartan Cilexetil in Phosphate buffer pH 6.8 at 254 nm
Figure. 3: UV Spectra of Candesartan cilexetil in Phosphate buffer pH 6.8
Figure 4: DSC of Candesartan Cilexetil
Figure 5: DSC of Candesartan Cilexetil + Plantago Ovata Seeds Mucilage + Fenugreek Seeds Mucilage
Figure 6: Ir Spectra of Candesartan Cilexetil
Figure 7: IR Spectra of Plantago Ovata Seeds Mucilage
Figure 8: IR Spectra of Fenugreek Seeds Mucilage
Figure 9: IR Spectra of Candesartan Cilexetil + Plantago Ovata Seeds Mucilage
Figure 10: IR Spectra of Candesartan Cilexetil + Fenugreek Seeds Mucilage
Table 5: Pre Compression Parameters of Candesartan Cilexetil Directly Compressible Granules
Batch |
Bulk density (gm/cc) |
Tapped density (gm/cc) |
Carr’s Index (%) |
Hausner’s ratio |
Angle of repose ( 0 ) |
CCMP1 |
0.398±0.004 |
0.410±0.0002 |
20.27 |
1.17 |
20.14 |
CCMP2 |
0.415±0.003 |
0.510±0.003 |
18.88 |
1.27 |
20.15 |
CCMP3 |
0.420±0.002 |
0.515±0.002 |
16.33 |
1.20 |
25.46 |
CCMP4 |
0.418±0.004 |
0.524±0.002 |
22.34 |
1.24 |
24.12 |
CCMF1 |
0.420±0.004 |
0.540±0.002 |
18.78 |
1.22 |
21.23 |
CCMF2 |
0.435±0.002 |
0.515±0.002 |
17.73 |
1.28 |
23.22 |
CCMF3 |
0.401±0.003 |
0.525±0.002 |
20.37 |
1.19 |
20.07 |
CCMF4 |
0.430±0.004 |
0.543±0.004 |
22.30 |
1.26 |
24.15 |
Table 6: Post Compression Parameters Candesartan Cilexetil MDT
Batch |
Thickness (mm) |
Hardness (kg/cm2) |
Friability (%) |
Weight variation (%) |
Drug content uniformity (%) |
CCMP1 |
4.74±0.012 |
2.47±0.05 |
0.316±0.001 |
246.66±1.032 |
97.71±0.254 |
CCMP2 |
4.75±0.016 |
2.47±0.05 |
0.311±0.004 |
246.66±1.032 |
98.35±0.110 |
CCMP3 |
4.71±0.056 |
2.12±0.04 |
0.331±0.033 |
248±0.063 |
98.59±0.159 |
CCMP4 |
475±0.0098 |
2.45±0.04 |
0.313±0.001 |
246.33±1.03 |
98.90±0.121 |
CCMF1 |
4.74±0.0081 |
2.47±0.05 |
0.316±0.003 |
246±1.15 |
97.77±0.351 |
CCMF2 |
4.74±0.009 |
2.43±0.04 |
0.316±0.001 |
245.66±1.03 |
98.04±0.489 |
CCMF3 |
4.75±0.004 |
2.47±0.05 |
0.317±0.002 |
246.05±0.59 |
98.30±0.210 |
CCMF4 |
4.73±0.047 |
2.48±0.05S |
0.298±0.034 |
245.16±0.98 |
98.77±0.204 |
Table 7, Post Compression Parameters of Candesartan Cilexetil MDT
Batch |
Wetting Time (sec) |
Water absorption ratio (%) |
Uniformity of dispersion |
Disintegration time (sec.) |
CCMP1 |
46.33±2.42 |
36.12±0.477 |
32.65±0.28 |
18.16±0.983 |
CCMP2 |
39.61±1.83 |
30.47±0.391 |
28.59±0.63 |
13±0.752 |
CCMP3 |
28.33±1.032 |
25.07±0.595 |
21.96±0.27 |
12±01.54 |
CCMP4 |
23±1.264 |
20.18±0.807 |
16.±0.11 |
8.66±0.81 |
CCMF1 |
45.05±2.45 |
82.90±0.25 |
31.58±0.94 |
40.85±0.429 |
CCMF2 |
45.83±2.41 |
87.90±0.91 |
31.96±0.98 |
32.06±0.638 |
CCMF3 |
42.33±1.982 |
89.20±0.97 |
33.17±0.61 |
26.16±0.233 |
CCMF4 |
35.42±1.051 |
91.48±1.98 |
21.88±0.28 |
21.32±0.178 |
figure.12: In Vitro Drug Release Profile of CCMP1-CCMP4
Figure.13: In Vitro Drug Release Profile of CCMF1-CCMF4
CONCLUSION:
· From the above results,candesartan cilexetil mouth dissolving tablets were prepared succesfully by using plantago ovata seeds and fenugreek seeds dried mucilage which are natural superdisintegranst, and alternative to the synthetic superdisintegrants, due to their non-toxic, low cost, free availability, emollient and no- irritant nature.
· Based on the results, formulation containing plantago ovata mucilage as superdisintegrant identified as ideal and better formulation among all the formulation. In vitro dissolution of candesartan cilexetil mouth dissolving tablets of CCMP4 was found to be, 98.16% within 15 min. with, in vitro disintegration time 8.66 sec. and CCMF3 having fenugreek mucilage as superdisintegrant shows highest dissolution 81.90% respectively, within 20 minutes. and in vitro disintegration time 26 sec.
· It was also concluded that isapghulla seeds dried mucilage as natural superdisintegrants showed rapid disintegration time and good release than fenugreek seeds dried mucilage.
AKNOWLEDGEMENTS:
We would like to thanks Mr. Sureshbhau Dhariwal Secretary JTES, SSJIPER Jamner, Dist- Jalgaon for providing necessary facility to carry out the work.
REFERENCES:
1. Kumar V. M., Formulation and Evaluation of Meclizine HCL Orally Dispersible Tablets by using Natural Super Disintegrants., International Journal of Pharmceutical Science & Resarch,2016, 53-80.
2. Sharma R., Rajput M., Fast Dissolving Drug Delivery System- A Review, International Research Journal of Pharmacy, 2011, 21-29.
3. Venkateswarlu K; Formulation and In-Vitro Evaluation of Mouth Dissolving Tablets of Ketoprofen: Effect of Disintegrants on Drug Release; Pharmatutor; 2017; 5(6); 17-21.
4. Shrisand S., Sarasija S., Plantago Ovate Mucilage in the Design of Fast Disintegrating Tablets, International Journal of Pharmaceutical sciences, 2009, 41-45.
5. Sttiraju V., Chandrashekhar K., Isolation and Characterization of Chemical Constituents from Trigonella -foneum graceum Seed Extract, International Journal of Pharmacognosy and Phytochemical Research,2014-15,715-718.
6. Rama Joga V., Inti G.,Venkatasubhramanian J., New Stability Indicating Method for Quantification of Impurities in Candesartan cilexetil & HcL Thiazide Tablets by Validated HPLC, International Journal of Pharmceutical Resarch Scholars, V-3, 2014, 2277-7873.
7. Kumar L, Singh V. and Meel R.; Formulation Development and Evaluation of Oral Disintegrating Tablet of Candesartan Cilexetil, World Journal of Pharmaceutical Research, , Volume 4, Issue 2, 2015, 1158-1170.
8. The Japanese Pharmacopoeia, 16th edition, Ministry of Health, Labour and Welfare, The Ministerial Notification No.65, April 2011, 512-513.
9. Bahadur S.,RoyA.,Chanda R., Baghel P., Assessment of Some Phytochemcial and Physicochemical Properties of Fenugreek Seed Mucilage, Research J. Pharm. and Tech,. 9(9): September 2016.
10. Khandelwal K.R., Sethi V., Practical Pharmacognosys-Techniques and Experiments, Nirali Prakashan, 24th Edition, August 2014.
11. Soni A, Thakur H, Dr. Goyal S And Singla S; Isolation and Characterization of Mucilage from Plantago Ovata, World Journal of Pharmaceutical and Life Sciences, Vol. 3, Issue 7,2017, 285-291.
12. Dhachiman .O., Venkateswaramurthy.N., Biopharmaceutics and Pharmacokinetics, A Practical Manual, Pharmamed Press Hydrabad,2010,1-4.
13. Gupta K.R, Wadodkar A.R., and Wadodkar S.G., UV Spectrometric Methods for Estimation of Valsartan in Bulk and Tablet Dosage Form, International Journal. Chem Tech Research, 2010, 2 (2):985-989.
14. Garg A., and M.M. Gupta, Mouth Dissolving Tablets: A Review, Journal of Drug Delivery & Therapeutics; 2013, 3(2), 207-214.
15. Indian Pharmacopoeia, Ministry of Health and Family Welfare, Govt. of The India, published by The Indian Phramacopoeial Comission, Ghaziabad, 2010, vol III : 2085-2087,Page no.02.
16. Lachman L and Liberman H., The Theory and Practice of Industrial Pharmacy, 3rd edition, Varghese, Publishing House, Bombay1987, 329-354.
17. Rao M.R., Madgulkar A.R., Warrier D., Advances in Drug Delivery-vol II, Pharmamade Publications, 1st edition, 1985,102-107.
Received on 02.06.2018 Accepted on 02.08.2018
© Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2018; 8(3): 136-144.
DOI: 10.5958/2231-5691.2018.00024.2