Comparative study of mode of addition of super Disintegrants on Methocarbamol tablets by Roller Compaction method

 

S. Madhavi Latha1*, J. Ramesh Babu2

1Department of Pharmaceutics, Aditya Pharmacy College, Aditya Nagar, ADB Road, Surampalem-533437, East Godavari District.

2Department of Pharmaceutics, CHIPS, Chowdavaram, Guntur.

*Corresponding Author E-mail: madhavilatha61@gmail.com

 

ABSTRACT:

Methocarbamol, a BCS class II drug is an antispasmodic agent used to treat the spasms from peripheral musculoskeletal conditions. The research focus in recent years has shifted to the formulation of both fast dissolving and disintegrating tablets that are swallowed and tablets that are intended to dissolving in the oral cavity. Super-disintegrants are now frequently used in tablet formulation to improve the rate and extent of tablet disintegration and thus improve the rate of drug dissolution. The majority of this research has been directed at the function-related properties of the super-disintegrants with special emphasis on correlating these properties to disintegrant efficiency and drug release. The present study was to formulate immediate release tablets using various types of disintegrants in order to investigate the effect of mode of incorporation of disintegrants on release of drug from tablets. Methocarbamol immediate release tablets were prepared by the roller compaction method by using a plasdone S630 as binder and four different disintegrants in combination of three modes of incorporation. The prepared tablets were characterized based upon their physicochemical characteristics. The results showed that F4 (CCS) and F7 (PP-XL) 3 % formulations exhibit faster release when compared to others. It may be concluded that intra-granular addition has given improved drug release from dosage form when compared to extra-granular and both intra and extra-granular addition.

 

KEYWORDS: Methocarbamol, Roller compaction method, Super-disintegrants, intra-granular mode of addition.

 

 

 


INTRODUCTION:

Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance and cost- effective manufacturing process. In spite of the increased focus and interest generated in the area of controlled release and targeted drug delivery system in recent years, tablet dosage forms that are intended to be swallowed whole, disintegrate, and release their medicaments rapidly in the gastrointestinal tract still remain the formulation of choice from both a manufacturing as well as patient acceptability point of view.

 

The research focus in recent years has shifted to the formulation of both fast dissolving and disintegrating tablets that are swallowed and tablets that are intended to dissolving in the oral cavity. Bioavailability of a drug depends on absorption of the drug, which is affected by solubility of the drug in gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. The drugs solubility mainly depends on physical - chemical characteristics of the drug. A drug given in the form of a tablet must undergo dissolution before being absorbed and eventually transported into systemic circulation. For most of the tablet dosage forms, disintegration precedes dissolution. Disintegrants are essentially added to tablet granulation for causing the compressed tablet to break or disintegrate when placed in aqueous environment1. Super-disintegrants are generally used at low level in solid dosage forms, typically 1-10% by weight relative to the total weight of dosage unit. Super-disintegrants such croscarmellose sodium, sodium starch glycolate (SSG), and crospovidone are now frequently used in tablet formulation to improve the rate and extent of tablet disintegration and thus improve the rate of drug dissolution. The behavior of super-disintegrants in various tablet formulation has been investigated by many researchers. The majority of this research has been directed at the function-related properties of the super-disintegrants with special emphasis on correlating these properties to disintegrant efficiency and drug release.

 

Methods of incorporating disintegrating agents into the tablet2:

There are three methods of incorporating disintegrating agents into the tablet-

a)  Internal addition (Intra-granular)

b)  External addition (Extra-granular)

c)  Partly Internal and External.

 

In external addition method, the disintegrant is added to the sized granulation with mixing prior to compression. In Internal addition method, the disintegrant is mixed with other powders before wetting the powder mixtures with the granulating fluid. Thus the disintegrant is incorporated within the granules. When these methods are used, part of the disintegrant can be added internally and part externally. This provides immediate disruption of the tablet into previously compressed granules while the disintegrating agent within the granules produces further erosion of the granules to the original powder particles. The two step method usually produces better and more complete disintegration than the usual method of adding the disintegrant to the granulation surface only.

 

Dry granulation method: 

When tablet ingredients are sensitive to moisture or are unable to withstand elevated temperatures during the drying, and when the tablet ingredients have sufficient inherent binding or cohesive properties, slugging may be used to form the granules. This method is referred as dry granulation, pre-compression or double-compression. It eliminates a number of steps but still includes weighing, mixing, slugging, dry screening, lubrication and compression.

 

Dry granulation has several advantages over wet granulation including

·        its usefulness with respect to ingredients that are sensitive to moisture or unable to withstand elevated temperatures during drying

·        it does not use organic solvents which may pose health and environmental hazards.

·        fewer steps involved in dry granulation than wet granulation.

 

Dry granulation by means of roller compaction is an efficient and useful method of granulation capable of handling a large amount of material in a short period of time (dry granulation by “slugging,” on the other hand, may be slow, inefficient, and many times requires several attempts at a successful formulation to ensure material flow). Zhihui Qiu et.al., (2009)3 studied that the roller compaction process has gained heightened interest in the pharmaceutical industry. In this review, common excipients and equipment used for dry granulation are described. Roller compaction process parameters and their impact on the critical quality attributes of the final product, as well as evaluation methods for roller compaction product such as ribbons and granules, are discussed. Overall, a systematical approach of formulation and process development has been proposed for excipient selection, critical process parameter identification, and necessary tests were conducted. B. Preetha et.al., (2008)4  studied the effect of mode of incorporation of superdisintegrants like croscarmellose sodium, sodium starch glycolate and crospovidone (polyplasdone XL and XL-10) on dissolution of three model drugs with varying aqueous solubility, like carbamazepine (poorly soluble), acetaminophen (sparingly soluble) and cetrizine HCl (soluble) from their respective tablet formulations prepared by wet granulation. The disintegrants were incorporated extragranularly or intragranularly or distributed equally between the two phases. The results indicated that Crospovidone in general was effective in improving the dissolution of the drugs used in the study and generally extra-granular mode of addition seemed to be the best mode of incorporation, irrespective of the solubility of the main tablet component. Lang12 showed that an equal distribution of super-disintegrant in both intragranular and extra-granular phases resulted in better dissolution than total incorporation.

 

Therefore, there is contradiction in the literature as to where the super-disintegrant should be distributed for the tablet dissolution to be optimized. The purpose of the present study is to compare the effect of mode of addition of different super-disintegrant and evaluate their effect on dissolution of poor soluble drugs.

 

Methocarbamol is a BCS class-II drug, having low aqueous solubility and high permeability. Its half life is 1-2 hrs which can be selected for immediate release formulation. In market, Methocarbamol is available in film coated tablets for which the onset of action is less when pain is severe while producing muscle relaxation. From this study we can measure the drug release that has been increased without using surfactants. The present study is to evaluate the disintegration and dissolution profiles of poorly soluble methocarbamol drug with intragranular or extra-granular alone, both intra and extra granular addition of super-disintegrants by   dry granulation (Roller compaction) technique5-7.

 

MATERIALS AND METHODS:

Methocarbamol was obtained as a gift sample from Granules India limited, Hyderabad. Cross-carmellose sodium (Ac-Di-Sol) was obtained from FMC biopolymers, Copovidone, Crospovidone (Polyplasdone XL) was obtained from ISP, Hyderabad. Sodium starch glycolate, Aerosil 200, Magnesium stearate, were purchased from S.D fine chemicals limited., Mumbai. All other chemicals used were of analytical reagent grade, available commercially and used as such without further processing.

 

Analysis of drug:

Simple High performance liquid chromatography method was developed for the determination of  Methocarbamol. Chromatography was performed on Alliance high performance liquid chromatograph equipped with Alliance chromatograph pump with 20 µl loop and Alliance Photo Diode Array detector. Stationary phase is symmetry c-18 column (250 X 4.0 mm, 5µ) at a column temperature of 30şc. Detection was performed at wavelength of 274 nm having flow rate 1ml/min. Mobile phase used is mixture of 75% pH 4.5 Buffer and 25% of Methanol.

 

Construction of calibration curve:

The standard calibration curve of Methocarbamol was prepared in distilled water. An accurately weighed 100 mg of Methocarbamol was dissolved in 100 ml of distilled water. This is stock solution I.  From this stock solution-I pipette out 2,4,6,8 and 10 ml solution take into 10ml volumetric flask and make up with distilled water. The concentrations of 200-1000ppm of Methocarbamol can observe in the wave length of 274nm and observe the peak areas by HPLC. A calibration graph of the peak areas versus the concentration of the drug was plotted.

 

Graph 1: Calibration curve of methocarbamol

 

Pre-formulation studies:

1. Physical Characterization of drug sample:

The pure API was analyzed and was found to comply for its identification and authenticity as per certificate of analysis provided by supplier. The drug was physically characterized according to following methods-

a) Description:

The received sample of API after visual observation and under compound microscope it was found to show the off-white colour, puffy like structure and these are acceptable according to COA of API.

 

b) Identification:

HPLC method:

HPLC chromatogram of the obtained sample of the drug was compared with the standard of the pure drug.       

 

Fig 1:  HPLC Chromatogram of Methocarbamol Standard

 

 

Fig 2:  HPLC Chromatogram of Methocarbamol sample

 

HPLC chromatogram of the obtained sample of the drug was matched with the standard chromatogram. It gives the retention time of 8.945 minutes.

 

Determination of melting point:

Melting point of API was determined by capillary method. Melting point of the pure API was found to be 90.5°C in the range of 90-94°C as reported in literature, thus indicating purity of the drug sample.

 

c) Loss on drying:

After drying 1.0 g of sample at 60°C for 3 hours in hot air oven. It was found that weight of sample reduced to 0.9977 g. LOD was found to be 0.23%.

 

d) Solubility:

Solubility can be readily done by placing the drug in a vial along with the solvent. The tightly closed vial is then agitated at constant temperature, and the amount of drug in solution is determined periodically by assay of filtrate sample of the supernatant. Solubility of drug substances was performed in Purified water, 0.1N HCL, Acetate buffer pH 4.5 and Phosphate buffer pH 6.8.

 

Graph 2: Solubility Profile of Methocarbamol

 

e) Particle size distribution was determined by Dry sieve analysis:

Each test sieve was sieved to the nearest 0.1 g. An accurately weighed quantity of test specimen was placed on the top (coarsest) sieve, and lid was replaced. The nest of sieves was agitated for 5 minutes. Then each sieve was carefully removed from the nest without loss of material. Each sieve was reweighed, and the weight of material on each sieve was determined. The weight of material in the collecting pan was also determined in a similar manner. The nest of sieves were reassembled and agitated for 5 minutes. Each sieve was removed and weighed, as previously described. Upon completion of the analysis, the weights of material were reconciled. Total losses must not exceed 5% of the weight of the original test specimen.

 

Table 1: Particle Size Distribution

Sieve no.

Arithmetic mean size of opening (µm)

Wt. retained on sieve (g)

Arithmetic mean size (µm*wt)

Average particle size(µg)

10

1700

0.490

833

 

∑nd/n =339.34 ±0.22

24

700

2.099

1469.3

40

325

7.179

2333.17

60

250

4.077

1019.25

85

180

3.701

486.18

100

150

0.986

147.9

120

125

-

-

 

Derived properties of API8:

Derived properties of the methocarbamol sample like angle of repose, bulk density and tapped density, carr’s index and hausner’s ratio were determined.

 

 

Table 2: Pre-formulation details of API

Wt. In (g)

Initial Vol. Vo(ml)

Final Vol. Vf (ml)

Bulk Density

30

71.5

59

0.4195

 

Table 2,, cont .......

Wt. In (g)

Tapped Density

Angle Of  Repose

Carr’s Index

Hausner’s  Ratio

30

0.5084

38.75

17.50

1.212

 

 

Drug-excipient compatibility studies9, 10:

The blend of drug with excipients in suitable ratio was filled in HDPE containers (for exposing to 40°C/75% RH) the mixture placed in glass vials to keep at 60°C for a period of 4weeks. After storage, the samples were observed physically for discoloration and degradation. The compatibility study is also evaluated by differential scanning calorimetric (DSC) analysis. Thermograms of drug with excipient were compared with the standard thermograms of the control sample. No physical changes were observed when physical mixture of drug with excipient after storage period of 4 weeks at 40°C / 75% RH. Hence the selected excipients are likely to be suitable for the preparation Methocarbamol tablets.

 

Differential scanning calorimetric (DSC) analysis:

The DSC thermo grams of pure drug and optimized formulation were as shown in figures.

 

 

Fig 3:Thermogram of Methocarbamol pure drug]

 

Fig 4: Thermogram of optimized formulation

 

Formulation of Methocarbamol tablets:

Methocarbamol has less flow properties and bulk density. In order to maintain the uniformity of the drug and enhancing the flow properties, we can go for granulation methods.

 

 

Table 3: Formulation of Methocarbamol tablets

Trials

IG

EG

F1

SSG (3%)

-

F2

-

SSG (3%)

F3

SSG (1.5%)

SSG (1.5%)

F4

CCS (3%)

-

F5

-

CCS (3%)

F6

CCS (1.5%)

CCS (1.5%)

F7

PP XL (3%)

-

F8

-

PP XL (3%)

F9

PP XL (1.5%)

PP XL (1.5%)

 

 

Table 4: Mode of addition of super disintegrants:

Ingredients

%w/w

mg/tab

Methocarbamol

92.5

500.0

Plasdone S630

3.00

16.2

Disintegrant*

3.00

16.2

Colloidal Silicon Dioxide

1.0

5.4

Magnesium Stearate

0.5

2.7

TOTAL

100

540.0

 

 

Preparation of methocarbamol tablets by Dry granulation (Roller compaction) method:

All the materials were weighed out as per the requirement. Methocarbamol was sifted through #750µm mesh. Plasdone S630 was sifted through # 425 µm mesh. Disintegrant was sifted through # 425 µm meshes. Colloidal Silicon dioxide was sifted through # 425 µm mesh. Magnesium stearate was sifted through #180 µm mesh. Before going for Roller compaction both sifted Methocarbamol and Plasdone S630 were blended for a time period of 5 minutes using double cone blender. In case of intra granular trials disintegrant was added to the above blend and blended for a time period of 5 minutes. Sifted Methocarbamol was passed through rollers at a compaction force of 200 psi initially and at a rollers speed of 6 rpm. The obtained flakes were sifted through #1.4mm mesh to make granules. Above granules were again passed through the rollers at a compaction force of 150 psi and rollers speed of 8 rpm and the obtained flakes were passed through #1.00 mm mesh to get uniform granules. Granules were pre lubricated with Colloidal silicon dioxide for a time period of 5 minutes. Magnesium stearate was added to the above blend and lubricated for a time period of 5 min. Final lubricated blend was compressed in to tablets using 11.5 mm round concave punches at a rotation speed of 8 rpm to get a tablet weight of 540 mg. Tablets were compressed at hardness range of 120-140N.

 

 

Evaluation tests for prepared Methocarbamol tablets:

The formulated tablets were evaluated for the following Pre, post compression quality control studies and dissolution studies.

 

Pre Compression studies:

Angle of Repose 11,12:

 It is defined as the maximum angle possible between the surface of a pile of powder and the horizontal plane. Angle of Repose of granules was determined by the funnel method.  Accurately weighed powder blend was taken in the funnel. Height of the funnel was adjusted in such a way the tip of the funnel just touched the apex of the powder blend. Powder blend was allowed to flow through the funnel freely on to the surface. Diameter of the powder cone was measured and angle of repose was calculated using the following equation.          

 

q = tan-1 (h/r)

Where:

q = Angle of repose

h = Height in cms

r = Radius in cms

 

The angle of repose has been used to characterize the flow properties of solids. It is a characteristic related to inter particulate friction or resistance to movement between particles.

 

Bulk density (BD):

It is the ratio of total mass of powder to the bulk volume of powder Weigh accurately 25 g of granules, which was previously passed through 22 # sieve and transferred in 100 ml graduated cylinder. Carefully level the powder without compacting, and read the unsettled apparent volume. Calculate the apparent bulk density in gm/ml by the following formula.

 

Bulk density = weight of powder / Bulk volume.

Db =

M = mass of the powder;

V0 = bulk volume of the powder.

 

Tapped density (TD): 

It is the ratio of total mass of powder to the tapped volume of powder weigh accurately 25 g of granules, which was previously passed through 22#  sieve and transferred in 100 ml graduated cylinder of tap density tester which was operated for fixed number of taps until the powder bed volume has reached a minimum, thus was calculated by formula.

 

Tapped density = Weigh of powder / Tapped volume

Dt =    (M) / (Vt) 

M = mass of the powder;

Vt = tapped volume of the powder.

 

Carr’s Index:

It is a simple test to evaluate the BD and TD of a powder and the rate at which it was packed down. The formula for Carr’s index is as below:

 

Compressibility index = 100 x

 

Hausner’s Ratio:

Hausner’s Ratio is a number that is correlated to the flow ability of a powder. 

 

Hausner’s Ratio   =

 

Post compression studies:

General appearance:

The formulated tablets were assessed for its general appearance and observations were made for shape, colour, texture and odour.

 

Weight Variation test 13:

20 tablets were selected and weighed collectively and individually.  From the collective weight, average weight was calculated. Each tablet weight was then compared with average weight to assure whether it was within permissible limits or not. Not more than two of the individual weights deviated from the average weight by more than 7.5% for 300 mg tablets and none by more than double that percentage.

 

Average weight = weight of 20 tablets

                                          20

%weight variation =   average weight - weight of each tablet   ×100

                                                     Average weight

 

 

Table 5: Acceptance criteria for tablet weight variation (USP 29-NF 34)

Average weight of tablet(mg)

% difference allowed

130 or Less than

± 10

130-324

± 7.5

More than 324

± 5

                         

Thickness 13:

Thickness of the tablets (n=3) was determined using a Vernier Callipers.

 

Hardness test 13:

Hardness of the tablet was determined by using the Monsanto hardness tester (n=3) the lower plunger was placed in contact with the tablet and a zero reading was taken. The plunger was then forced against a spring by turning a threaded bolt until the tablet fractured. As the spring was compressed a pointer rides along a gauge in the barrel to indicate the force.

 

Friability test 13:

This test is performed to evaluate the ability of tablets to withstand abrasion in packing, handling and transporting.

 

Initial weight of 20 tablets is taken and these are placed in the Friabilator, rotating at 25 rpm for 4 min.

 

The difference in the weight is noted and expressed as percentage.

It should be preferably between 0.5 to 1.0%.

 

%Friability = [(W1-W2)/W1] X 100

Where, W1= weight of tablets before test,

W2 = weight of tablets after test

 

Assay of tablets:

The assay sample was prepared by finely powdering 20 tablets of each formulation using mortar and pestle. Accurately weighed and transferred a portion of the powder equivalent to 100 mg of Methocarbamol in to 100 mL volumetric flask. To it 70 ml of mobile phase was added and kept in an ultrasonic bath for 20 minutes. Then the volume was made up to the mark with the mobile phase and mixed well.

 

Instrumental Conditions for assay:

The Assay of the samples was performed using the HPLC instrumental conditions mentioned below.

Mobile phase

:

75% pH 4.5 Buffer and 25% of Methanol.

Flow rate

:

1.0 ml/min

Column

:

Symmetry-C18, 250 X 4.0 mm, 5µ

Column temperature

:

30°C

Injection volume

:

20 µl

Detector wavelength

:

274 nm

Runtime

:

20.0 minutes

RT

:

8.5-9.5minutes

 

Disintegration test13:

The disintegration test was carried out using USP disintegration test apparatus type-2. Six tablets were placed individually in each tube of disintegration test apparatus and discs were placed over each tablet. Distilled water was used as the medium maintained at 370c ± 0.50c and the time taken for each tablet to disintegrate completely was recorded.

 

In vitro Dissolution Study:

Instrumental Conditions for assay:

The Assay of the samples was performed using the HPLC instrumental conditions mentioned below.

 

 

 

Mobile phase

:

75% pH 4.5 Buffer and 25% of Methanol.

Flow rate

:

1.0 ml/min

Column

:

Symmetry-C18, 250 X 4.0 mm, 5µ

Column temperature

:

30°C

Injection volume

:

20 µl

Detector wavelength

:

274 nm

Runtime

:

20.0 minutes

RT

:

8.5-9.5minutes

 

 

RESULTS AND DISCUSSION:

Evaluation of pre-compression properties Methocarbamol tablets:

Physical properties such as bulk density, tapped density, angle of repose, compressibility index and hausner’s ratio were determined for the prepared tablet blend.

 


Table 6: Pre-compression studies of Dry granulation blends

Batch

Angle of Repose

(0) ± S.D

Bulk Density

(g/cc) ± S.D

Tapped Density

(g/cc) ± S.D

Carr’s index 

± S.D

Hausner’s ratio ± S.D

F1

32.00±0.29

0.490±0.006

0.5320±0.001

7.857±0.05

1.085±0.03

F2

30.92±0.67

0.512±0.001

0.5420±0.004

5.535±0.05

1.058±0.03

F3

30.92±0.67

0.501±0.002

0.5300±0.004

5.471±0.05

1.058±0.03

F4

26.61±0.45

0.503±0.002

0.5432±0.003

7.363±0.04

1.079±0.05

F5

30.02±0.55

0.456±0.003

0.4997±0.001

8.745±0.03

1.095±0.06

F6

30.02±0.55

0.445±0.003

0.4872±0.001

8.661±0.03

1.095±0.06

F7

28.01±0.46

0.514±0.001

0.5485±0.003

6.289±0.02

1.067±0.02

F8

32.20±0.43

0.502±0.004

0.5550±0.003

9.477±0.03

1.104±0.04

F9

28.01±0.46

0.510±0.005

0.5505±0.002

7.193±0.06

1.077±0.06

 

 

Table 7: Evaluation of Methocarbamol tablets prepared by Roller compaction method

Batch

Thickness (mm) (n=3)

Hardness (N) (n=3)

Avg. Wt (mg) (n=20)

%

Friability

In vitro disintegration time (sec)

% Drug content

F1

5.35±0.07

125-140±4.62

539±2.18

0.048

36±2.4

98.9±0.40

F2

5.50±0.08

127-140±4.22

540±3.15

0.059

32±1.8

100.5±0.19

F3

5.32±0.06

121-137±4.37

540±3.12

0.047

33±2.0

99.7±0.21

F4

5.40±0.06

125-141±4.50

541±2.19

0.043

22±1.2

100.9±0.15

F5

5.60±0.08

123-141±5.25

539±2.75

0.054

58± 3.9

100.4±0.45

F6

5.38±0.08

   121-140±6.79

540±2.70

0.051

30 ±5.2

100.4±0.32

F7

5.48±0.07

   121-141±6.22

542±2.60

0.049

25 ±3.2

100.5±0.19

F8

5.22±0.10

120-139±5.13

540±3.10

0.057

35 ±2.5

100.4±0.16

F9

5.50±0.10

123-142±7.28

539±3.18

0.051

41±3.2

99.7±0.21

 

 

 


DISCUSSION:

The dry granulation blends showed the angle of repose values in the range from 26.61 ± 0.45 to 32.20 ± 0.43. All formulations showed excellent to good flow ability. The granulation blends showed bulk density and tapped density in the range from 0.445±0.003 to 0.512±0.001 and 0.4872±0.001 to 0.5550±0.003gm/ml respectively having good packability of the granules. The carr’s index of the granulation blends were in the range from 5.471± 0.05 to 8.661 ± 0.03. All formulations showed excellent to good compressibility. The Hausner’s ratios of dry granulation tablet blends were found to be in the range from 1.058 ±0.03 to 1.095 ± 0.06. All formulations showed excellent to good flow property.  

 

Evaluation of Post-compression properties:

The prepared tablets were evaluated for average weight, weight variation, thickness, hardness, friability, assay, in-vitro disintegration time, and in-vitro drug release for all the batches.

 

DISCUSSION:

The tablets have showed the thickness ranges from 5.22±0.10 to 5.60±0.08. The dry granulated tablets have showed the hardness ranges from 120-139±5.13 to 127-140±4.22 N. All the formulations Methocarbamol tablets pass the weight variation test and they showed the %deviation of tablets within the IP limit of ±5%. The tablets were showed the friability ranges from 0.043 to 0.059. All the formulations showed the faster disintegration times. Among all F4 and F7 formulations showed faster disintegration than all the remaining i.e., with in 22 and 25 sec respectively. Among all, both PP XL and CCS were showing the fastest dissolution compared to others. This mode of addition yields the fastest dissolution rate of the three modes of addition. Intra granular addition was the effective mode of addition for both PP XL and also for CCS. The tablets were showed the assay values from 98.9 to 100.5%.

 

 

 

In Vitro Dissolution test:

Dissolution test was carried out on 3 tablets from every formulation prepared by roller compaction method and reported as percent drug release with respect to time. The drug release profiles of intra granular mode of addition of three disintegrants were provided here.

 

Graph 3: Intragranular PP XL,CCS and SSG at 3% level

 

Discussion:

The release profiles of Intra-extra granular combinations of both PP XL and CCS were lying in between the release profiles of complete intra and complete extra granular additions. The more release in case of intra granular addition can be attributed to the necessity of full disintegration of the granules in to powder. Adding more disintegrant in to the inner phase would lead to a faster dissolution rate.

 

Comparison of best formulations with innovator product (Robaxin 500mg):

The formulation containing intragranular addition of Polyplasdone XL and CCS were showing the fastest dissolution compared to other. So the formulations F4 and F7 were compared with marketed tablet Robaxin 500mg for in-vitro disintegration and dissolution studies.

 

Graph 4: Comparison of disintegration time of  F4 and F7 with Robaxin 500mg

Comparison of dissolution profiles of optimized formulations, F4 and F7 with Innovator product, Robaxin 500 mg:

The dissolution profile comparison can be done using simple model independent approach. This approach uses a difference factor (f1) and a similarity factor (f2). Generally f1 values < 15 and f2 values > 50 ensure sameness or equivalence of two curves. They are expressed using following equations

f1= {[St=1n (Rt-Tt)]/St=1n Rt]}*100

f2= 50* log {[1+ (1/n) St=1n (Rt-Tt) 2]-0.5 *100}

 

Where; n is the number of time points, Rt is the mean percent drug release of reference product, Tt is the mean percent drug release of test product.

 

Graph 5: Comparison of dissolution profiles of F4 andF7 with Robaxin

 

Table 8: Similarity and Differential factors of optimized formulations.

Formulation

f 1

f 2

F4

3.37

67.22

F7

1.45

73.63

Discussion:

Comparison of methocarbamol IR tablets T9 and T11 with marketed film coated tablet Robaxin 500mg showed the better results with respect to disintegration and dissolution profiles. They showed disintegration time 3 times less than marketed sample and gave % of drug release comparable to marketed product, it shows improved results when compared to marketed product.   

 

SUMMARY AND CONCLUSION:

HPLC chromatogram of the obtained sample of the drug was matched with the standard chromatogram. It gave the retention time of 8.945 min. The flow properties of the sample were found to be poor. Comparison of the thermo grams obtained from DSC studies showed that there was no interaction between the API and the excipients. The flow properties of all the formulation blends were found to be good. All the formulations passed the weight variation test. The tablets have showed the thickness ranges from 5.29±0.07 to 5.60±0.0.04 and breaking force ranges from 119±5.27 to 142±7.38. The tablets were showed the friability ranges from 0.043±0.004 to 0.063±0.001 and assay values from 98.9±0.40 to 101.2±0.21. The prepared tablets have showed the disintegration time ranges from 18 to 110 sec.  Among all, both PP XL and CCS were showing the fastest dissolution compared to others. This mode of addition yields the fastest dissolution rate of the three modes of addition. Intra granular addition was the effective mode of addition for both PP XL and also for CCS. The release profiles of Intra extra combinations of both PP XL and CCS were lying in between the release profiles of complete intra and complete extra granular additions. The more release in case of intra granular addition can be attributed to the necessity of full disintegration of the granules in to powder. Adding more disintegrant in to the inner phase would lead to a faster dissolution rate. The formulations F4 and F7 were compared with marketed tablet Robaxin 500mg for in-vitro disintegration and dissolution studies.

 

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Received on 29.04.2017           Modified on 31.05.2017

Accepted on 09.06.2017          © RJPT All right reserved

Research J. Pharm. and Tech. 2017; 10(7): 2194-2202.

DOI: 10.5958/0974-360X.2017.00387.0