Taste Masked Orodispersible Tablet Of Cefadroxil Biology Essay

Published:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

Cefadroxil orodispersible tablets were established with significant increase in drug release as related to marketed formulations, seven formulations were developed and considered. The modification in drug release values was found to be 100.34 ± 2.87 and 65.57 ± 2.86, correspondingly. To inhibit bitter taste and offensive odour of the drug, the drug was taste masked with weak cation exchange resins like Indion 234, Indion 204 and Indion 414. The drug was characterized according to several compendial methods, on the basis of identification by UV spectroscopy, pH, organoleptic properties and further tests. Among the three resins, one was designated for further studies i.e., Indion 234, due to high drug loading ability. Drug-resin complex was arranged using batch method and influence of several processing parameters viz. drug-resin ratio, pH, temperature and drug concentration was considered to elevate the loading circumstances. Determined loading was obtained at drug-resin ratio 1:2, pH 5, temperature 50ËšC and drug concentration 4 mg/ml. A successful taste masking of resinate was definite by time intensity method and also by taking drug release in phosphate buffer pH 5 and in simulated salivary fluid. The values of pre-compression parameters estimated, were in prescribed limits and showed decent free flowing properties. The statistics obtained of post-compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution and was establish greater over predictable formulation. The F5 batch with disintegration time 25.22 ±0.65 and dissolution 100.34% ± 2.87 was selected as optimized formulation. This was matched with conventional marketed formulation and was found greater. Batch F5 was also exposed to stability studies for three months and was tested for its disintegration time, drug contents and dissolution behaviour monthly. It was observed that the contents of the tablets persisted the same. By an applicable selection and combination of excipients it was probable to obtain orodispersible and taste masked tablets.

Keywords: Cefadroxil, Orodispersible tablet, Taste masking, Ion exchange resin.

1. Introduction

Cefadroxil are wide spectrum antibiotic used to treat a wide variety of infections [1]. This medicated combination operates by inhibiting the reproduction of the bacteria and the production of its cell walls together (Fig.1). Recently, European Pharmacopoeia has used the term ''Orodispersible tablet'' for tablets that dissolves readily and within 3 min in mouth before swallowing [5]. United States Food and Drug Administration (FDA) defined ODT as ''A solid dosage form containing medicinal substance or active ingredient which disintegrates fast usually within a matter of seconds when placed upon the tongue'' [4]. Fast Disintegrating and/ or dissolving tablets are best substitute to deliver the drug having bitter taste and poor oral bioavailability. FDTs (Fast Disintegrating/ Dissolving Tablets) can be prepared by several methods as direct compression, wet granulation freeze-drying, spray drying and sublimation method. The simplicity and cost efficiency of the direct compression process have positioned this method as an attractive alternate to traditional granulation technologies [3].

Figure 1. Inhibition of Bacterial cell wall synthesis

Taste masking of the drug employing ion exchange resins (IER) has verified to be safe and actual method for formulation of different dosage forms. Taste masking by ion exchange resin i.e., Indion 234 was active because of its well drug loading and taste masking. Ion exchange resins have been gradually used for the taste masking of bitter taste drug and help to make orodispersible tablets [6]. Ion exchange resins are solid and suitable in solubilised high molecular weight polyelectrolytes that can alter their mobile ions of equal charge with the adjacent medium reversibly and stotiometrically. They are available in preferred size ranges. Bitter cationic drugs can acquire adsorbed on to the weak cationic exchange resins of carboxylic acid functionally to form the complex which is not bitter. Further resonates can be expressed as lozenges, chewing gum, suspension or dispersible tablet and mask the taste [7]. Drug can be bound to the resin with the drug solution. Drugs are devoted to the oppositely charged resin substrate or resonate through weak ionic bonding so that detachment of the drug- resin complex does not occur under salivary pH conditions. This appropriately masks the unpleasant taste and odour of drugs [8]. Taste masking is an important requirement for fast dissolving tablets for viable success. Taste masking of the active ingredient can be achieved by various techniques.

2. Materials and methods

2.1. Materials:

All materials used in the present research were commercial samples. Active agent: Cefadroxil (Lupin Pvt. Ltd., India), ION Exchange Resins: Indion 204, Indion 234 and Indion 414 (ION Exchange India Ltd., Mumbai, India); Excipients: Microcrystalline Cellulose, Croscarmellose Sodium, Sodium Starch Glycolate, Avicel Microcrystalline Cellulose, Kollidon, Calsium alginate, Lactopress Anhydrous and Croscarmellose Sodium, were gift by were received from Colorcon Asia (Mumbai, India).

2.2. Preparation of tablets:

The preparation of tablets was carried out after the investigation of drug samples, ion exchange resins, mixture formation and their analysis, drug loading studies, formulation and evaluation of Tablets [9].

2.2.1. Analysis of Cefadroxil:

The cefadroxil was characterized according to different compendial methods and was found to be a white to off-white, crystalline powder with characteristic odour. Found to have a melting point in range of 192-198Ëš C and a pH of 4-6, kmax of 263 nm, and all the findings matched the official reports.

2.2.1.1. Scanning of Cefadroxil phosphate buffer pH 5.0

The solution containing 20 µg/ml of cefadroxil in phosphate buffer pH 5.0 was prepared and scanned over range of 263 nm against phosphate buffer pH 5.0 as a blank using double beam UV spectrophotometer. The kmax was found to be 263.0 nm, which approves to the reported value.

2.2.1.2. Preparation of dissolution medium for standard curves

In the current work, cefadroxil was estimated by UV spectrophotometry in distilled water, phosphate buffer pH 5.0, phosphate buffer pH 5.0 and in simulated salivary fluid.

2.2.1.3. Preparation of standard calibration curve in distilled water

Various drug concentrations (5-50 µg/ml) in distilled water were prepared and the absorbance was measured at 263 nm. For the standard curve, 100 mg of cefadroxil was accurately weighed and dissolved in 100 ml of distilled water, and then 5 ml of the resulting solution was diluted to 100 ml with distilled water to make stock solution of concentration 50 µg/ml. Further serial dilutions were carried out with distilled water to get drug concentrations 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 µg/ml. The absorbance of dilutions was measured against distilled water as a blank at 263 nm using double beam UV/Visible spectrophotometer. The plot of absorbance Vs concentration was plotted and subjected to linear regression analysis. Drug was establish to obey Beer Lambert's law in the concentration range of 5-50 µg/ml.

2.2.1.4. Preparation of standard calibration curve in simulated salivary fluid

Various drug concentrations (5-50 µg/ml) in simulated salivary fluid were prepared and the absorbance was measured at 263 nm [10]. For the standard curve, 100 mg cefadroxil was precisely weighed and dissolved in 100 ml of simulated salivary fluid, and then 5 ml of the resulting solution was diluted to 100 ml with simulated salivary fluid. Further serial dilutions were carried out with simulated salivary fluid to get drug concentrations 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 µg/ml. The absorbance of dilutions was measured against simulated salivary fluid as a blank at 263 nm using double beam UV/visible spectrophotometer. The plot of absorbance Vs concentration was plotted and exposed to linear regression analysis. Drug was found to obey Beer Lambert's law in the concentration range of 5-50 µg/ml.

2.2.2. Analysis of ion exchange resin (IER):

The IER is selected on the basis of drug nature and rations of the formulation. The study was carried out among three altered resins viz. Indion 204, Indion 234 and Indion 414 in order to screen most suitable resin for complexation with cefadroxil. Resinates were prepared using batch process. In each case, 100 mg cefadroxil in deionised water was stirred with 100 mg of resin using magnetic stirrer at 500 rpm. The amount of drug loaded at the end of 45 min was determined indirectly by estimating the extent remaining to be loaded in solution spectrophotometrically at 263 nm [11].

2.2.2.1. Effect of drug: resin ratio

The Indion 234 which showed highest amount of drug loading for ratio 1:1 was elevated for various drug: resin ratios. In each case, 100 mg of cefadroxil was stirred with varying amount of resin in deionised water using magnetic stirrer at 500 rpm. The volume of drug loaded at

Time

(min)

Percentage of drug loaded

A B C D

00 00 00 00 00

10 26.46 ± 0.25 41.61 ± 0.46 60.17 ± 0.53 63.58 ± 0.26

20 38.2 ± 0.45 54.86 ± 0.70 75.7 ± 0.93 77.97 ± 0.46

30 42.17 ± 1.84 60.35 ± 1.39 86.63 ± 1.39 83.6 ± 0.71

40 44.45 ± 1.38 76.40 ± 2.32 87.06 ± 2.78 84.08 ± 4.64

50 43.88 ± 0.91 77.97 ± 2.78 88.77 ± 1.85 84.65 ± 0.92

60 43.31 ± 2.30 77.97 ± 3.24 88.2 ± 0.46 85.09± 5.10

Table 1. Effect of drug-resin ratio

different time intervals was determined indirectly by estimating the amount remaining to be loaded in solution spectrophotometrically at 263 nm. A plot of mean of three determinations for percentage drug loaded as a function of time is plotted in (Fig. 2.) Results are displayed in (Table 1).

Figure 2. Effect of drug-resin ratio.

2.2.2.2. Effect of pH on drug loading

The study was carried out at five pH values 3, 4, 5, 6 and 7. The pH was adjusted to desired

value using 2 N citric acid. Solution of 100 mg cefadroxil drug was stirred with 200 mg of resin using magnetic stirrer at 500 rpm. The amount of drug loaded at various time intervals was determined indirectly by estimating the amount remaining to be loaded in solution spectrophotometrically at 263 nm. A plot of mean of three determinations for percentage drug loaded as a function of time at different pH was obtained.

2.2.2.3. Effect of temperature on drug loading

The study was carried out at four temperature conditions 30Ëš C, 40Ëš C, 50Ëš C and 60Ëš C. In each case, 100 mg of cefadroxil was stirred with 200 mg of resin in deionised water using magnetic stirrer at 500 rpm. The amount of drug loaded at various time intervals was determined indirectly by estimating the amount remaining to be loaded in solution spectrophotometrically at 263 nm. A plot of mean of three determinations for percentage drug loaded as a function of time was acquired.

2.2.2.4. Effect of drug concentration on drug loading

The study was carried out at three different concentrations 2 mg/ml, 4 mg/ml and 6 mg/ml. In each case, solution equivalent to 100 mg drug was stirred with 200 mg resin in deionised water using magnetic stirrer at 500 rpm. The amount of drug loaded at different time intervals was determined indirectly by estimating the amount remaining to be loaded in solution spectrophotometrically at 263 nm. A plot of mean of three determinations for percentage drug loaded as a function of time was acquired.

2.2.2.5. Optimized conditions

Following are the optimum conditions for the preparation of drug-resin complex of cefadroxil and are best suited for optimum loading

(1) Drug: resin ratio: 1:2

(2) pH: pH 5

(3) Drug concentration: 4 mg/ml

(4) Time: 30 min

2.2.2.6. Preparation of drug-resin complex

In batch process, 200 mg of activated resin was placed in a beaker containing deionised water and allow to swell for 30 min. Accurately weighed cefadroxil 100 mg was added and stirred for one hour. The combinations were filtered and residue was washed with deionised water. DRC was then washed with sufficient quantity of deionised water for three times to remove loosely adsorbed drug from resinate surface. DRC was endorsed to dry at room temperature and was stored in tightly closed container and used in additional studies.

2.2.3. Studies on drug - complexes:

2.2.3.1. Drug release from DRC

Drug release from DRC was determined using United States Pharmacopoeia (USP) type I dissolution apparatus. DRC equivalent to 30 mg of resinate was weighed accurately and added to 900 ml of phosphate buffer pH 5.0 and maintained at 37Ëš C. Drug release was performed at 50 rpm for 15 min. Aliquots of the medium were withdrawn at regular intervals, filtered and the absorbance determined on spectrophotometer. From absorbance values, percent drug dissolved at various time intervals was determined. A plot of mean of three determinations for percentage drug released as a function of time is plotted in (Fig. 3) and results are exhibited in (Table 2).

Figure 3. Drug release from DRC.

Sr. No. Time (min) Percentage drug release

1 0 0

2 2 30.77 ± 6.63

3 4 73.99 ± 7.55

4 6 86.33 ± 5.77

5 8 94.62 ± 3.93

6 10 96.37 ± 2.88

7 12 96.57 ± 2.18

8 15 97.35 ± 2.88

Table 2. Drug release from DRC.

2.2.3.2. Taste panel evaluation of different batches of resinate

In this the different batches of resinate were tested to decide most suitable ratio of complex for successful taste masking.

Batch Taste-masked Taste panel

A Yes Not acceptable worst than B

B Yes Not acceptable better than A

C Yes Maximum acceptability

D Yes Maximum acceptability

Table 3. Taste panel evaluation.

The results (Table 3) showed exceptional correlation with the evaluation of the taste panel employed. From above observations, Formulation C was selected for further study.

2.2.3.3. Taste panel evaluation for 'Batch C' resinate

Bitterness was quantitated by consensus of competent taste panel. A time intensity method was used, in which a sample equivalent to a normal dose was held in the mouth for 10 s [12]. Bitterness level were recorded immediately, and then spat out (Table 4). A numerical scale was used with the following values:

tasteless, 0.5-very slight, 1-slight, 1.5-slight to moderate,

2- moderate, 2.5-moderate to strong, 3-strong, 3+-very strong.

Sr. No. Volunteers 10 s 1 min 2 min 5 min 10 min 15 min

1 1 0.6 ± 0.67 0.4 ± 0.31 0.1 ± 0.24 0.3 ± 0.58 0.2 ± 0.14 0

2 2 0.8 ± 0.58 0.2 ± 0.4 0 0.3 ± 0.58 0 0

3 3 0.5 ± 0.37 0.4 ± 0.44 0 0 0 0

4 4 0 0.4 ± 0.4 0 0 0 0

5 5 0 0.5 ± 0.37 0 0 0 0

6 6 0 0 0 0 0 0

7 7 0.3 ± 0.37 0 0 0.1 ± 0.3 0 0

8 8 0 0 0 0 0 0

9 9 0 0 0 0 0 0

10 10 0 0 0 0 0 0

Table 4. Taste panel evaluation for 'Batch C' resinate.

2.2.3.4. 'In vivo' evaluation of drug complex

The said resinate was given to panel of healthy human volunteers for taste masking evaluation using time intensity method which shows adequate masking of taste (Table 5).

Form of doxylamine

Succinate

Degree of bitterness (Time)

10 s 1 min 2 min 5 min 10 min 15 min

Pure drug 2.1 ± 0.53 2.7 ± 0.14 2.4 ± 0.44 1.6 ± 0.87 1.0 ± 0.48 0.6 ± 0.40

Drug-resin complex (c) 1.0 ± 0.63 0.7 ± 0.67 0 0 0 0

Table 5. In vivo evaluation of drug complex.

2.2.3.5. 'In vitro' evaluation of drug content

Drug release from the DRC was also performed in 10 ml of pH 5 solution by adding drug complex equivalent to 10 mg of cefadroxil to a test tube. The mixtures were filtered after shaking for 60 s. The filtrates were assayed for drug. Drug resonates are insoluble hence, even resinate of bitter drugs have effectively no taste. With the correct selection of ion exchange resin, the drug is not released in the mouth so that the patient does not taste the drug when it is swallowed. The percentage drug dissolved was found to be 1.96% ± 0.50 at a drug-resin complex ratio of 1:2.

2.2.4. Formulation of orodispersible tablets:

Cefadroxil orodispersible tablets were prepared according to the formula given in (Table 6). A total number of seven formulations were prepared. All the ingredients were passed through 60 mesh sieve individually and collected. The ingredients were weighed and mixed in a geometrical order. First MCC, Lactose and crospovidone were mixed together. Drug complex was then added and was mixed for 10-15 min. Finally to this blend aspartame and magnesium stearate were added and mixed further for 10-15 min [12].

Sr. Table ingredients (mg)

No.

Formulation

F1 F2 F3 F4 F5 F6 F7

1 DRC 40 40 40 40 40 40 40

2 Microcrystalline cellulose 244.32 - 122.16 162.88 183.24 81.44 61.08

3 Lactose - 244.32 122.16 81.44 61.08 162.88 183.24

4 Calcium alginate 9.12 9.12 9.12 9.12 9.12 9.12 9.12

5 Magnesium stearate 2.80 2.80 2.80 2.80 2.80 2.80 2.80

6 Aspartame 3.75 3.75 3.75 3.75 3.75 3.75 3.75

7 Flavour (Vanilla) q.s q.s q.s q.s q.s q.s q.s

Table 6. Formulation composition.

The tablets were then compressed using 10 mm size punches to get a tablet of 300 mg weight. The data for the selection of various superdisintegrants and their concentration for series F1-F12 are given as supplementary data before tablet preparation, the mixture blend of all the formulations were subjected to pre-compression parameters like angle of repose, bulk density, tapped density,% compressibility and flowability. The orodispersible tablets prepared subjected to post-compression parameters like, content uniformity, hardness, friability, weight variation, dissolution and in vitro disintegration. Batches were equipped by direct compression method. Direct compression is the preferred method for preparation of tablets. Current usage of the term ''direct compression'' is used to define the process by which tablets are compressed from the powder blends of active ingredient/s and suitable excipients. No pre-treatment of the powder blends by wet or dry granulation is involved.

2.2.5. Evaluation of blend for orodispersible tablets:

Blend was evaluated for flow properties.

2.2.5.1. Angle of repose

The flow characteristics are measured by angle of repose. Improper flow of powder is due to frictional forces between the particles. These frictional forces are quantified by angle of repose. Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder and the horizontal plane.

By definition

Tan θ = h/r

θ = tan- 1 h/r

where h is the height of pile;

r is radius of the base of the pile;

θ is the angle of repose.

2.2.5.2. Bulk density.

It is defined mathematically as

Bulk density (Ç·) = Mass of powder (w)/ Bulk volume (V b)

A powder (about 60 g) is passed through a standard sieve No. 20. A weighed quantity (approximately 50 g) is introduced into a 100 ml graduated cylinder. The cylinder is fixed on the Bulk density. Apparatus and the timer knob is set (regulator) for 100 tappings. The volume occupied the powder is noted. Further, another 50 taps may be continued and the final volume is noted. For reproducible results, the process of tapings may be continued until concurrent volume is achieved. This final volume is the bulk volume. Then bulk density is calculated using equation. Bulk volume is also measured by dropping the cylinder (containing powder) onto a hard wooden surface 3 times from a height of 1 inch at 2 s intervals. Sometimes, to get an appropriate volume, the container has to be dropped or tapped 500 times.

2.2.5.3. Tapped density.

Tapped density was determined by USP method II. The powder sample under test was screened through sieve No. 18 and 10 g of tablet bend was filled in 100 ml graduated cylinder of tap density tester (Electrolab, ETD 1020). The mechanical tapping of the cylinder was carried out using tapped density tester at a nominal rate of 250 drops per minute for 500 times initially and the initial tapped volume (Va) was noted. Tapping was proceeded further for additional 750 times and volume was noted. The difference between two tapping volumes was calculated. Tapping was continued for additional 1250 times if the difference is more than 2%. This was continued in increments of 1250 taps until difference between volumes of subsequent tapings was less than 2%. This volume was noted as, the final tapped volume (Vb).

The tapped density (Dt) was calculated in g/ml by the formula,

Dt = M/Vb

where M is the weight of sample powder taken; Vb is tapped volume.

Determinations were carried out in 3 replicates. The mean value of three determinations are considered.

2.2.5.4. Compressibility

Carr's consolidation index: It is defined as:

Consolidation index = tapped density - fluff density/ tapped density - 100

Compressibility index can be a ration of the potential strength that a powder could build up in its arch in a hopper and also the ease with which such an arch could be broken. Using a suitable adhesive, the base of a 10 ml tarred measuring cylinder is fixed to the standard rubber bung at the top of the 250 ml cylinder. A powder sample (about 5.0 g) is transferred into the tarred 10 ml cylinder with the help of a funnel. The 250 ml measuring cylinder is placed on the tapping apparatus. The initial volume occupied by the powder is denoted as V0. The contents are tapped in the following order, 2, 4, 6, 8, 10, 20, 30 and 50 taps. After completing the tapings, the volume is denoted as V2, V4 . . . V50. The powder is carefully collected from the cylinder and weighed (W)

Fluff density (Ç· b minimum ) = W /V0 g /cc

Tapped density ( Ç· b maximum) = W /V50 g /cc

2.2.5.5. Powder flowability

Before tablating the flowability of the mixture ingredients of each formulation was studied. Though the pure cefadroxil was non flowable the addition of excipients resulted in a formation with percent compressibility between 12-16 and angle of repose between 20-30 indicating that flowability had expressively enhanced (Table 7).

2.2.6. Evaluation of tablets:

The formulated orodispessible tablet were evaluated for different parameters like, weight variation [13], hardness, friability, wetting time [14], water absorption ratio [15], content uniformity and dissolution [16].

2.2.6.1. Weight variation

With a tablet intended to contain a specific amount of drug in a specific amount of tablet formula, the weight of the tablet being made is routinely measured to help ensure that a tablet contains the proper amount of drug. In practice, composite samples of tablets (usually 10) are taken and weighed throughout the compression process. The composite weight divided by 10, however, affords an average weight but contains the usual complications of averaged values. Within the composite sample that has an acceptable average weight, there could be tablets excessively overweight or underweight. To help alleviate this problem the United States

Formulations

Property

Angle of Bulk Tapped % compressibility Flowability

repose density density

gm/cm3

F1 24.55 ± 0.71 0.55 ± 0.012 0.65 ± 0.002 13.16 ± 1.2 Good

F2 23.12 ± 0.75 0.55 ± 0.013 0.67 ± 0.011 13.46 ± 1.4 Good

F3 25.24 ± 0.82 0.56 ± 0.016 0.66 ± 0.024 14.26 ± 1.1 Good

F4 24.87 ± 1.76 0.55 ± 0.014 0.64 ± 0.021 13.76 ± 1.5 Good

F5 26.60 ± 0.43 0.58 ± 0.011 0.63 ± 0.013 13.36 ± 1.0 Good

F6 25.71 ± 1.63 0.57 ± 0.012 0.66 ± 0.014 13.46 ± 1.3 Good

F7 26.42 ± 1.14 0.57 ± 0.010 0.65 ± 0.015 13.76 ± 1.7 Good

Table 7. Evaluation of mixed blend of drug and excipients.

Pharmacopoeia (USP)/National Formulary (NF) provides limits for the permissible variations in the weights of individual tablets expressed as a percentage of the average weight of the sample. The USP weight variation test is run by weighing 20 tablets individually, calculating the average weight, and associating the individual tablet weights to the average. The tablets meet the USP test if no more than 2 tablets are outside the percentage limit and if no tablet differs by more than 2 times the percentage limit. The weight variation tolerances for uncoated tablets differ reliant on average tablet weight.

2.2.6.2. Hardness

The hardness of a tablet is suggestive of its tensile strength and is measured in terms of load/pressure required to crush it when placed on its edge. A number of handy hardness testers such as Mosanto type or Pfizer type are currently in use. Hardness of about 5 kg is considered to be minimum for uncoated tablets for mechanical stability. The hardness is a function of physical properties of granules like their hardness and deformation under load, binders and above all the compressional force. The hardness has influence on disintegration

and dissolution times and is as such a factor that may affect bioavailabilities.

2.2.6.3. Friability

Generally it refers to loss in weight of tablets in the containers due to removal of fine particles from their surfaces. However, in wider sense chipping and fragmentations can also be included in friability. Friability generally reflects poor cohesion of tablet ingredients. Standard devices have been fabricated to measure friability. Generally such instruments, marketed as 'Friability Test Apparatus' or 'Friabilators', consist of a circular plastic chamber, divided into 2-3 compartments. The chamber rotates at a speed of 25 r.p.m. and drops the tablets by a distance of 15 cm. Pre weighed tablets are placed in the apparatus, which is given 100 revolutions after which the tablets are weighed once again. The difference in the two weights represents friability. The weight loss should not be more than one per cent.

2.2.6.4. Wetting time and water absorption ratio

The procedures similar to those used Bi et al., where used to measure tablet wetting time and water absorption ratio. A piece of tissue paper folded twice was placed in a small petridish containing 6 ml of water. A tablet was kept on the paper and time necessary for complete wetting was measured. The wetted tablet was then weighed. Water absorption ratio, R, was determined using the subsequent equations:

R = {(W a - W b) - W b} - 100

where, W b = weight of tablet before water absorption, and

W a = weight of tablets after absorption.

2.2.6.5. Disintegration time.

In vitro disintegration time of tables from each formulation were determined by using digital

tablet disintegration apparatus. In vitro disintegration test was carried out at 37± 2Ëš C in 900 ml distilled water.

2.2.6.6. Content uniformity.

Transfer one finely powdered tablet to a 100 ml volumetric flack containing 65 ml of phosphate buffer pH 5.0, Shake frequently during a 10 min period, dilute with phosphate buffer pH 5.0, and mix. Allow the insoluble material to settle, and filter, discarding the first 20 ml of the filtrate. Dilute a portion of the subsequent filtrate quantitatively and stepwise, if necessary, with phosphate buffer pH 5.0 to provide a solution containing approximately 25 µg of cefadroxil per ml. Concomitantly determine the absorbances of this solution and of a standard solution of USP cefadroxil RS in the same medium having a known concentration of about 25 µg per ml in 1-cm cells at the wavelength of maximum absorbance at about 263 nm, with a suitable spectrophotometer, using phosphate buffer pH 5.0 as the blank. Calculate the quantity in mg, of C16 H17 N3 O5 S in the tablet taken by the formula: (TC/D) (AU/AS)

Formulation

Parameters

Weight Hardness Friability Disintegration Content Wetting % Water

Variation kg/cm2 % time (s) uniformity time absorption ratio

F1 Passes 4.12±0.2 0.77±0.01 31.52±0.4 96.51±0.3 10.03±1.4 90.62± 0.32

F2 Passes 4.22±0.2 0.75±0.01 56.51±0.4 96.93±0.3 10.43±1.4 92.54± 0.32

F3 Passes 4.02±0.2 0.75±0.01 45.53±0.4 97.25±0.3 11.83±1.4 98.34± 0.32

F4 Passes 4.15±0.2 0.76±0.01 31.42±0.4 98.01±0.3 11.93±1.4 100.64± 0.32

F5 Passes 4.05±0.2 0.75±0.01 25.22±0.4 98.81±0.3 10.71±1.4 101.44± 0.32

F6 Passes 4.12±0.2 0.71±0.01 48.82±0.4 98.89±0.3 11.63±1.4 70.34± 0.32

F7 Passes 4.42±0.2 0.72±0.01 56.08±0.4 98.30±0.3 12.23±1.4 113.64± 0.32

Table 8. Evaluation of orodispersible tablet.

in which; T is the labeled quantity in mg, of cefadroxil the tablet, C is the concentration, in µg/ml of USP cefadroxil RS in the standard solution, D is concentration, in µg/ml cefadroxil in the solution from the tablet, based on the labeled quantity per tablet and the extent of dilution and AU and AS are the absorbances of the solution from the tablet and the standard solution, respectively, results are reported in (Table 8).

2.2.6.7. Dissolution studies.

The in vitro dissolution studies were carried out using USP apparatus type I at 50 rpm. The dissolution medium used was phosphate buffer pH 5.0 (900 ml) maintained at 37 ± 0.5Ëš C. Aliquots of dissolution media were withdrawn at different intervals and content of cefadroxil was measured by determining absorbance at 262 nm (Table 9).

Time (min)

Formulation

F1 F2 F3 F4 F5 F6 F7

0 00 00 00 00 00 00 00

2 20.74±11.3 28.46±6.4 36.95±13.3 40.81±6.3 40.80±4.5 41.26±3.8 40.03±1.9

4 51.61±3.9 45.43±1.2 50.84±13.2 57.79±5.6 66.26±1.4 62.41±7.5 56.24±3.3

6 71.67±9.4 67.05±3.7 71.36±11.3 73.99±7.5 90.18±5.7 80.15±5.7 78.61±3.7

8 82.47±2.8 92.50±1.8 93.05±8.5 84.02±2.8 97.13±3.7 97.13±1.8 92.50±7.6

10 94.82±3.8 92.50±7.6 91.50±3.7 97.14±1.9 100.2±1.8 97.90±2.8 94.04±2.8

12 94.81±1.9 90.18±5.7 91.52±7.6 97.14±3.8 101.0±3.9 97.92±1.9 94.81±1.9

15 94.82±7.6 92.58±9.5 91.53±5.7 97.91±1.9 100.3±3.7 98.67±2.8 74.81±5.7

Table 9 Dissolution study of different batches

The dissolution experiments were conducted in triplicate. Not less than 80% (Q) of the labeled amount of C16 H17 N3 O5 S is dissolved in 30 min. The comparative results are shown as (Fig. 4).

Figure 4. Dissolution study of different batches

2.2.6.8. Comparison of optimized formulation with conventional marketed tablet.

In vitro dissolution studies for batch F5 and conventional tablet were carried out using USP apparatus type I at 50 rpm, which shows that the drug release was more than 80% within 15 min which is better than conventional marketed tablet. The results are a plot of comparison is shown in (Fig. 5).

Figure 5. Comparison of optimised formulation with conventional marketed tablet.

2.2.6.9. Stability study.

Stability study was carried by storing tablets at 40 C ± 2ËšC % relative humidity for three months [17]. The content and dissolution behaviours from orodispersible tablets were tested monthly for three months (Tables 10 and11).

Sr. No. Evaluation 1 month 2 month 3 month

1 Hardness 3.8 ± 0.16 4.1 ± 0.11 4.1 ± 0.18

2 Disintegration time 24.6 ± 0.43 26.2 ± 0.76 27.2 ± 0.43

3 Content uniformity 98.2 ± 0.14 97.8 ± 0.18 98.5 ± 2.09

Table 10. Stability data for 40Ëš C.

Sr. No. Time (min)

Cumulative % drug release

1 month 2 month 3 month

1 0 0 0 0

2 2 18.65 ± 6.0 25.60 ± 3.9 23.28 ± 5.7

3 4 30.23 ± 9.7 40.26 ± 1.3 38.78 ± 6.4

4 6 57.24 ± 3.3 70.35 ± 5.7 54.92 ± 2.8

5 8 76.52 ± 2.8 87.33 ± 4.5 77.30 ± 5.6

6 10 94.27 ± 7.5 98.13 ± 3.8 92.73 ± 3.3

7 12 99.67 ± 2.8 101.1 ± 2.8 99.67 ± 1.9

8 15 99.67 ± 1.9 100.4 ± 1.9 99.67 ± 2.8

Table 11. Dissolution profile for 40Ëš C.

Figure 6. Dissolution profile for 40Ëš C.

Each tablets was individually weighed and wrapped in a aluminium foil and packed in black PVC bottle and put at above specified conditions in a heating humidity chamber for three months. After each month tablet sample was analysed for hardness, disintegration, time, dissolution and drug content. The results are shown below, comparative account is given in the form of plots (Fig. 6).

3. Result and discussion

The formulation of orodispersible tablet was finished by using cefadroxil-resin complex (resinate C). Batches F1- F7 were ready by direct compression to select the disintegrant, from the results. It can be concluded that the tablets enclosing calcium alginate (batch S6 and S7) exhibit rapid disintegration time and followed by tablets enclosing croscarmelleose sodium and sodium starch glycolate. The apparent reason for delayed the disintegration time of the tablet might be slow water uptake or more gelling affinity of croscarmellose sodium and sodium starch glycolate than calcium alginate. Hence, calcium alginate was designated as a disintegrant for the further studies. From the results it was evident that the optimum concentration of calcium alginate be less than 10%. Batches F8-F12 were prepared to optimize the optimum concentration of calcium alginate in order to obtain quick disintegration at minimum concentration. Batches F6 (48.82 ± 0.48), F7 (56.08 ± 0.84) and F8 (46.55 ± 0.39) showed decrease in disintegration time and wetting time (10-12 s). But F8 had shown additional decrease in disintegration time and wetting for this reason batch S8 was selected. In batch F7 disintegration time (56.08 ± 0.84) was found more than batch S8, such behaviour of superdisintegrants may be due to the blockade of capillary pores which avoids the entry of fluid into the tablet. For formulation of orodispersible tablet the blend was prepared and subjected to evaluation. The composition of blend of each batch is given in (Table 6). The tablet blend of all the batches were evaluated for several derived properties viz.-angle of repose (between 23 and 26), Bulk density (between 0.55 and 0.57 gm/cm3), Tapped Density (0.63-0.67 gm/cm3), Compressibility index (between 13 and 14, and flowability (good). The results of Angle of repose and compressibility specified that the flowability of blend is significantly good. Orodispersible tablets were prepared in batches F1-F7 and evaluated for tablet properties like, weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution. All the tablets passed weight variation test as the percent weight variation was within the pharmacopoeial limits. Hardness were shown in the range of 4.05 ±0.26-4.42 ± 0.11 kg/ cm2 in all the formulations which showed good mechanical strength with an ability to withstand physical and mechanical stress conditions while handling. In all the formulations, the friability value was less than 1% and meets the official limit. The results of disintegration of all the tablets were found to be within approved limits and fulfilled the criteria of Orodispersible tablet. The values were found to be in the range of 25.24± 0.75-56.08 ±1.04. The percentage drug content of all the tablets was found to be between 97.92 ±0.32 and 98.89 ± 0.13 of Cefadroxil which was within acceptable limit. All the tablets prepared were subjected for release profile. The tablets prepared from crospovidone i.e., F1- F7 showed a drug release between 74.81 ± 2.87 and 100.03 ± 3.92. The wetting time and water absorption ratio was also in acceptable limit i.e., between 10.03 ± 1.44- 12.24 ± 1.01 and 70.3 ± 0.34-113.63 ± 0.63. Among seven Batches, Batch F5 is selected as optimized batch because of its lowest disintegration time and highest drug release. In comparison, formulation F5 was compared with conventional marketed formulation. The drug release of marketed product and F5 formulation was found to be 65.57 ± 2.86 and 100.37 ±2.87 at the end of 15 min. Stability was performed on formulation F5. Results for hardness, disintegration time, dissolution and content uniformity show no appreciable change up to 3 months of accelerated stability studies.

Conclusion:

Ion exchange resins are solid and appropriately insoluble high molecular weight polyelectrolytes that can exchange their mobile ions of equal charge with the surrounding medium. The resulting ion-exchange is reversible and stoichiometric with the displacement of one ionic species by another. Three Superdisintegrants were screened in order to determine most suitable Superdisintegrant, among these, 9% w/w calcium alginate was designated and strained for additional studies. A total number of seven formulations were ready by direct compression technique. In the end of it can be concluded that pharmaceuticals complexes using ion exchange resins have shown developed organoleptic performance of pharmaceuticals and well patient compliance. This study shows an urgent need for a new dosage form which can expand patient compliance.

Writing Services

Essay Writing
Service

Find out how the very best essay writing service can help you accomplish more and achieve higher marks today.

Assignment Writing Service

From complicated assignments to tricky tasks, our experts can tackle virtually any question thrown at them.

Dissertation Writing Service

A dissertation (also known as a thesis or research project) is probably the most important piece of work for any student! From full dissertations to individual chapters, we’re on hand to support you.

Coursework Writing Service

Our expert qualified writers can help you get your coursework right first time, every time.

Dissertation Proposal Service

The first step to completing a dissertation is to create a proposal that talks about what you wish to do. Our experts can design suitable methodologies - perfect to help you get started with a dissertation.

Report Writing
Service

Reports for any audience. Perfectly structured, professionally written, and tailored to suit your exact requirements.

Essay Skeleton Answer Service

If you’re just looking for some help to get started on an essay, our outline service provides you with a perfect essay plan.

Marking & Proofreading Service

Not sure if your work is hitting the mark? Struggling to get feedback from your lecturer? Our premium marking service was created just for you - get the feedback you deserve now.

Exam Revision
Service

Exams can be one of the most stressful experiences you’ll ever have! Revision is key, and we’re here to help. With custom created revision notes and exam answers, you’ll never feel underprepared again.