Research Articles

2017  |  Vol: 3(6)  |  Issue: 6 (November-December)
Formulation and evaluation of colon specific drug delivery of Eterocoxib by using Okra Gum

Chindam Suresh*, Kondapuram Parameshwar, Kosika Sandeep

Department of Pharmaceutics, School of Pharmacy, Gurunanak Institute of Technical Campus, Hyderabad, TelanganaIndia.

*Address for corresponding Author

Chindam Suresh

Assistant Professor

School of Pharmacy, Guru Nanak Institutions Technical Campus, Hyderabad, Telangana, India


Abstract

Objective: Design and  development  of  okra  gum  based  colon  specific  tablet formulations for chronotherapeutic delivery  of drugs, Eterocoxib  for  the  treatment  of  diseases. Materials and methods: The gum extracted from thoroughly washed, sliced and crushed fruits with a laboratory blender. After extraction the precipitate of the gum  were  dried  in  hot  air  oven  for  about  20min  at  50C  and  then precipitates were kept in a dessicator for further drying Etoricoxib, HPMC, E.C other formulation excipients. The in vitro dissolution test has been performed in 0.1 N HCl for first two hours and the rest in 6.8 pH phosphate buffer using USP apparatus type II (paddle), at 50 rpm for six hours. The  spectrum  was  measured  in  the  solid  state  as  Potassium  bromide dispersion..The Press coated tablets were prepared by varying polymer (HPMC): polymer (E.C) ratio i.e., 4:0, 3:1, 2:2, 1:3, 3:1 and 0:4. Results and conclusion: The drug release from the  dosage forms was started after 4hrs lag time.The Press coated tablets obtained by 3:1 ratio (P2F9) shows good lag time, more % drug released immediately  after lag time  in comparision with those prepared by 4:0, 2:2, 3:1, 0:4  hence P2F9. It has been concluded from the above investigation that Press coated dosage form of Etoricoxib could delay the release up to 4hrs and further exhibited immediate release of the drug and shows 20 hr action. The results obtained in this research work clearly indicated a promising potential of colon specific drug delivery of eterocoxib by using okra gum containing HPMC, HPMS EC, as a rate controlling polymer for the effective treatment of rheumatoid patients.

Keywords: HPMC, HPMC, E.C, Okra Gum, colon specific drug delivery


Introduction

Oral drug delivery  system is the  most commonly used route for drug delivery  due  to  its  ease  of  administration,  better  patient  compliance,  and  flexibility  in  design  and  development  of  formulation.  The  drug  delivery  to  the  colon  has attracted a lot of attention of the scientist working on oral drug delivery system which  is  mainly  due  to  the  fact  that  colon  is  a  site  where  both  local  and systemic drug delivery can take place (Bussemer et al., 2001). In recent times the  colon-specific  drug  delivery  systems  are also  gaining  importance  for  the systemic  delivery  of  proteins  and  peptide  drugs.  Due  to  negligible  activity  of brush  border  membrane  peptidase  activity  and  less  activity  of  pancreatic enzymes, the colon is considered to be more suitable for delivery of protein and peptide in comparison to small intestine Besides this low hostile environment, the colonic transit time is long (20-30 h) and the colonic tissue is highly responsive to the action of absorption enhancers The  longer  residence time, less  peptidase  activity,  natural  absorptive  characteristics  and  high response to absorption enhancers make colon a promising site for the delivery of protein and peptides, oral vaccines, insulin, growth hormone, erythropoietin, interferons  and  interleukines.

Colonic delivery can be accomplished by oral or rectal administration.  Rectal dosage forms such as suppositories and enemas are not always effective since a high variability in the distribution of these forms is observed and enema solutions can only offer topical treatment to the sigmoid and descending colon. Therefore, oral administration is preferred, but for this purpose, many physiological barriers have to be overcome. Absorption or degradation of the active ingredient in the upper part of the GIT is  the  major  obstacle  and  must  be  circumvented  for  successful  colonic  drug Delivery.

Figure 1. Anatomy of human gastrointestinal tract (Friend and Tozer, 1992).

 

Table 1.  Anatomical  and  physiological  features  of  small  intestine  and colon

Region of gastrointestinal tract

Length (cm)

Entire gastrointestinal tract

500-700

Small intestine

 

Duodenum

Jejunum

Heum

20-30

150-200

200-350

Large intestine

 

Caecum

Ascending colon

Transverse Colon

Descending colon

Sigmoid colon

Rectum

Anal canal

6-7

20

45

30

40

12

3

Materials and methods

Isolation of Okra Gum

Unripe  and  tender  fruits  of Okra  were  purchased  from  a  local  market.  A 3kg weight of fruits were thoroughly washed, sliced and crushed with a laboratory blender (Jyoti Pvt Ltd. Vadodara). The  obtained  paste  was  macerated  in distilled  water  for  24h  in  the  presence  of  0.1%  wt/vol  sodium  metabisulphite (an antioxidant). Expression was done  with  a  clean  muslin  cloth by  placing  a little quantity of the paste in the cloth and  then  expressed  so  that the gum exuded from it. Precipitation of the extract was done with acetone, by adding a little  quantity  of  the  extract  in  a  beaker  containing  20mL of  acetone  and  the mixture was stirred using glass rod for about 3min. The precipitated gum was transferred  into  another  beaker  containing  fresh  acetone  and  stirred continuously (30min)  until  the  gum  was  completely  precipitated. The precipitates were dried in hot air oven for about 20min at 50°C and then precipitates were kept in a dessicator for further drying. Drying continued until constant weight was obtained. 

Phytochemical Examination

Following chemical tests were conducted to evaluate the phytochemical nature of obtained OG (Table 2). These were Ruthenium red test, Molisch test, Ninhydrin test and test for reducing sugars.

Table 2. Chemical tests for phytochemical examination of gum

Tests

Reagents

Composition

Test for presence of

Positive test

Ruthenium red test

Ruthenium red

-

Mucilage

Red color

Molish test

Molish’s reagent

A solution of napthol in 95% ethanol

Carbohydrate

Purple ring at the interface between the acid and test layers

Ninhydrin test

Ninhydrin reagent

2,2-Dihydroxyindane-1,-dione

Ammonia or primary and secondary amines

Blue to blue violet color

Test for reducing sugars

Fehling I

7g Of Hydrated Copper (Ii) Sulfate Dissolved In 100 Ml Of Dist.Water

Reducing Sugar

Brick red precipitate.

-

Fehling II

35 g of potassium sodium tartrate and 10 g of sodium hydroxide in 100 ml of dist.water

Reducing Sugar

-

Swelling index

One  gram  sample  was  placed  in  25mL graduated  plastic  centrifuge  tubes and the  volume  occupied  was  noted.  10mL of  distilled  water  was  added  and  the content  was  allowed  to  swell  for  1h  with  the  vigorous  shaking  at  the  time interval  of  10min.  Mixture  was  allowed  to  stand  for  10min  followed  by centrifugation  at  1000rpm  for  10min  on  a  bench centrifuge. The supernatant was carefully decanted and volume of sediment was measured. The swelling index was computed using following equation (Bapat S 2004).

S= V2/V1         --------------(1)

Where S= Swelling index

V1= Volume occupied by the gum prior to hydration

V2= Volume occupied by the gum after hydration

Swelling index was determined for three times for the same sample of OG by keeping the conditions constant.

Loss on drying

The adopted method is specified in the British Pharmacopoeia 2007 for acacia.Same  procedure  was  used  to  determine  loss  on  drying  for  Og.  According  to which  petridish  was  dried  under  the  condition  prescribed  for  the  substance  to be  examined.  One  gram of  sample was  transferred  into  dried  petridish  which was then dried in an oven at 105°C until the weight of content became constant. The moisture content was determined as the ratio of weight of moisture loss to weight of sample expressed as a percentage. Loss on drying was determined for three times for the same sample of OG by keeping the conditions constant. 

Total ash and acid insoluble ash determination

Ash content was estimated by the measurement of residue left after combustion of  two  grams  (W) of  gum  in  a  tared  crucible  in  a  furnace  at  temperature  not exceeding  450°C  to  get  carbon  free  residue  which  was  cooled  and  weighed (W2).

The  obtained  ash  was  boiled  with  25mL  of  2M  hydrochloric  acid solution for 5min. The content was filtered. After filtration, the insoluble matter was washed with hot water and resultant product was ignited.  After ignition, residues were obtained.  The weight of residues (W3) was determined and percent acid insoluble ash was alculated. The total ash and acid insoluble ash were  determined  for  three  times  for  the  same  sample  of  OG  by  keeping  the conditions constant. 

The percentage of total ash of the sample was calculated by given equation [2]:

(W2/W1) x 100--------------(2)

The percentage of acid insoluble ash of the sample was calculated by given equation (3):                          

(W3/W1) x 100--------------(3)

Analytical method for the estimation of Etoricoxib

Determination of λ max for Etoricoxib (Mukherjee and Desiraju, 2012)

On the basis of preliminary identification test, it was concluded that the drug complied the preliminary identification. From the scanning of drug, it was concluded that the drug had λ max of 234.5 nm which was nearer to 234 nm as reported.

Preparation of standard calibration curve of Etoricoxib

The standard calibration curve for Etoricoxib was prepared using pH 6.8 phoshate buffer solution.

Standard solution: The 25 mg of Etoricoxib was dissolved in 25 ml pH 6.8 phosphate buffer solution to give a concentration of 1 mg/ ml (1000 µg/ml).

Stock solution: From standard solution take 5 ml of solution in 50 ml of pH 6.8 phosphate buffersolution to produce the 50 µg/ml concentration and take from the 50 µg/mlof the solutionaliquots of 1, 2, 3, 4, and 5 ml of stock solution was pipette out in 10ml volumetric flask.The volume was made up to mark with 6.8 buffer solution to produce concentration as 2, 4, 6, 8, and 10 µg/ml of Etoriccoxib respectively.

The absorbance of prepared solution of Etoriccoxib was measured at 234 nm in Shimadzu UV/visible 1700 spectrophotometer against pH 6.8 phosphate buffer solution as blank. The absorbance data for standard calibration curve are given in Table 4 and plotted graphically as shown in the Figure 4. The standard calibration curve yields a straight line, which shows that drug obeys Beer’s law in the concentration range of 2 to 10 µg/ml.

Formulation of core tablets

Table 3. Composition of different core tablet formulations

Ingredients (mg)

F 1

F 2

F 3

F 4

F 5

F 6

F7

F8

F9

F10

Etoricoxib

50

50

50

50

50

50

50

50

50

50

Lactose Monohydrate

150.2

145.8

140.3

150.2

145.8

140.3

150.2

145.8

140.3

156.8

Talc

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

Magnesium stearate

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

PVP

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

4.4

SSG

6.6

11

16.5

-

-

-

-

-

-

-

CCS

-

-

-

6.6

11

16.5

-

-

-

-

CP

-

-

-

-

-

-

6.6

11

16.5

-

Total Weight

220

220

220

220

220

220

220

220

220

220

Formulation of core tablets by wet compression method

The inner core tablets were prepared by using  direct compression method.As  Shown in table  4 powder mixtures  of etoricoxib, pvp,talc, crospovidone, lactulose monohydrate  ingredients were dry blended for 20 min  followed by addition of MgStearate. The  mixtures  were then  further  blended for 10 min., 200mg of resultant powder blend  was  manually  compressed using KBr  hydraulic  press at a pressure of 1 ton, with a 8mm punch and die to obtain the core tablet.

Table 4. Formulation of coating polymer for Press coat method

Press coat

F11

F12

F13

F14

F15

HPMC

400mg

300mg

200mg

100mg

0mg

Okra Gum

0mg

100mg

200mg

300mg

400mg

Total wt

400mg

400mg

400mg

400mg

400mg

Formulation of mixed blend for barrier layer

The various formulation compositions were containing Okra Gum and HPMC. Different compositions were weighed dry blended at about 10 min and used as Press - coating material to prepare press - coated pulsatile tablets respectively by direct compression method.

Preparation of press-coated tablets

The core tablets were press-coated with 400mg of mixed blend/granules as givenin Table 6. 200mg of barrier layer material was weighed and transferred into a  13 mm die then the core tablet was placed manually at the center. The remaining 200mg of the barrier layer materiel was added into the die and compressed at a pressure of 5tons for 3min using KBr hydraulic press.

Evaluation of rapid release core (RRCT) and press-coated tablets Of Etoricoxib

Sieve Analysis

The procedure involves the Electromagnetic Sieve shaking of the sample through the series of successively arranged sieves (sieve no. - 20, 30, 40, 60, 80, and receiver), and weighing of the portion of the sample retained on each sieve and calculate percentage retained on each sieve.

Flow properties

Angle of Repose (θ)

These are the simple and related techniques for measuring the resistance to particle moment. Angle of repose is defined as the maximum angle possible between the surface of a pile of powder and horizontal plane,                                              

Tan θ = h/r

θ = tan-1 h/r

Where h =height of pile

r =radius of base of pile

θ =angle of repose

Method: A glass funnel is held in place with a clamp on a ring support over a tile Approximately 100gms of powder is transferred into funnel through a mesh size number 20 keeping the orifice of the funnel blocked by the thumb.

When the powder is emptied from the funnel, the angle of the heap to the horizontal plane is measured with a scale. The height of the pile (h) and the radius at the base is measured with a ruler. The angle of repose is thus estimated

Angle of repose limits are mentioned in the table 5

Table 5. Relationship between angle of repose (θ) and powder flow

Angle of repose (θ) degrees

Flow

<25

Excellent

25-30

Good

30-40

Passable

>40

Very poor

Compressibility index

It is the propensity of a powder to be compressed. It is measured by tapped density apparatus for 500, 750 and 1250 taps for which the difference should be not more than 2 %. Based on the apparent bulk density and tapped density the percentage compressibility of the blend was determined using the following formula. 

Table 6. Acceptance limits for Consolidation index

Consolidation index

Flow

5-15

Excellent

12-16

Good

18-21

Fair to passable

23-35

Poor

33-38

Very poor

>40

Very very poor

Hausner’s ratio

It indicates the flow properties of the powder. The ratio of tapped density to the bulk density of the powder is called Hausner ratio.

Bulk Density

Bulk density of a compound varies substantially with the method of crystallization, milling or formulation. Bulk density is of great importance when considers the size of high dose capsule product or homogenicity of allow dose formulation in which these are large differences in drug and excipient densities Bulk density is determined by graduated cylinder containing a known mass of powder whose initial volume is noted. Cylinder is fixed on the mechanical tapper apparatus. Then the final volume is noted, and this bulk volume. Then bulk density is calculated is using

Weight variation       

Twenty tablets were randomly selected from each batch weighed individually. The average weight and standard deviation was calculated         .

Thickness 

Three tablets from each batch of formulation  were  collected  and  the  thicknesses  of  the  tablets  were measured  with  the  help  of  Verniercaliper.  The average thickness was calculated.   

Hardness

Hardness was measured using Monsanto tablet hardness tester. The hardness of five tablets in each batch was measured and the average hardness was calculated in terms of  kg/cm2.

Friability (F)   

Friability of the tablet determined using Roche friabilator. Pre-weighted sample of tablets were placed in the friabilator and were subjected to the 100 revolutions. Tablets were dusted using a soft muslin cloth and reweighed.

Wetting time             

Wetting time of dosage form is related to the contact angle. A piece of tissue paper folded twice was placed in a small petridish containing 6 ml of water. Tablet was kept on the paper and the time for complete wetting was measured.  The mean ± SD values were calculated accordingly.

Drug content

For determination of drug content at least five tablets from each formulation were weighed individually, crushed and diluted to 100 ml with sufficient amount of phosphate buffer of pH 6.8 in a volumetric flask. Then aliquot of the filtrate was diluted suitably and analyzedspectrophotometrically at 234 nm against blank. Drug content was calculated using standard curve.

Disintegration  time for  RRCTs    

To test the disintegration time of tablets, one tablet was placed in each tube and the basket  rack  was  positioned  in  a  1  liter  beaker  containing phosphate buffer pH 6.8 at 37°C ± 1°C such that the tablet remains 2.5 cm below the surface of the liquid. The time taken for the complete disintegration of the tablets was noted.

In-vitro release studies for RRCTs

Tablet was introduced into the basket of the LABINDIA TS 8000 USP dissolution test apparatus and the apparatus was set in motion at 50 rpm for time period of 1hrs, 5 ml of sample was withdrawn for every 5min intervals and replaced by pH 6.8 phosphate buffer solutions. Samples withdrawn were analyzed by UV spectrophotometer for presence of drug using buffer solution as blank.

In-vitro Dissolution methods for press-coated tablets

In vitro Dissolution  studies  of  Pulsatile  delivery  systems  was done with  the conventional paddle method of press coated tablets were performed at 37  ± 0.5 °C using 0.1%hcl for 2hrs followed by 6.8 buffer in USP II paddle method at 50 rpm. 5 ml of filtered aliquot was manually withdrawn at pre-determined time intervals and replaced with 5 ml of fresh 6.8 buffer solution maintained at the same temperature. The samples were analysed at 234nm using a UV spectrophotometer. The lag time and percentage release was determined of the each formulation.

Stability Studies

The stability study of the formulations was carried out according to ICH guidelines at 40 ± 2 °C/75 ± 5 % RH for one month by storing the samples in stability chamber (Lab-care, Mumbai).

Compatibility Studies

FT-IR Spectra: The Infra-red studies were performed by the instrument Shimadzu Corporation japan. In this, enough samples are placed on the crystal area, and the pressure arm should be positioned over the sample area. Force is applied to the sample, pushing it onto the diamond surface. Later the sample is analysed. The same procedure is repeated for analysis of pure drug, excipients and mixture.

Results and discussion

Okra gum: Phytochemical examination

Table 7. Chemical tests for phytochemical examination of okra gum powder

Tests

Observations

Inference

Ruthenium red test

Red color

Mucilage

Molisch test

Purple ring at the interface between the acid test layers

Carbohydrate

Ninhydrin test

No Blue to blue violet color

Absence of amino acid

Test for reducing sugars

 

 

Benedict’s reagent

Blue to green/yellow orange/red/brown

Reducing sugars

Fehling I

Brick red precipitate

Reducing sugars

Fehling II

Brick red precipitate

Reducing sugars

Table 8. Physicochemical characterization

Parameters

Okra gum

Solubility

Slightly soluble in water.Practically insoluble in ethanol, acetone and chloroform

Swelling index

pH1.2

2.25 ± 0.2

pH 7.4

2.38±0.3

pH 6.8

2.15±0.2

Distilled water

2.22±0.5

Loss on drying

0.89 ±0.01%

Total ash

1.8±0.03%

Acid insoluble ash

0.6 ±0.03%

Angle of repose

32±0.11̊

pH

6.8±0.54

Bulk density

0.72±0.021 g/cm3

Tapped density

0.84±0.031 g/cm3

Compressibility index

14.3 ±0.014%

Hausner’s ratio

1.16 ±0.014

Standard calibration curve of Etoricoxib

The standard calibration curve for Etoricoxib was prepared using pH 6.8 phoshate buffer solution. The absorbance of prepared solution of Etoricoxib was measured at 234 nm in Shimadzu UV/visible 1700 spectrophotometer against pH 6.8 phosphate buffer solution as blank. The drug showing linearity up to 10 µg/ml.

Table 9. Linearity values for Etoricoxib

S.No

Concentration (µg/ml)

Absorbance (nm)

1.

0

0

2.

2

0.1406

3.

4

0.2846

4.

6

0.4346

5.

8

0.6323

6.

10

0.8131    

Figure 2. Standard plot of Etoricoxib in pH 6.8 phosphate buffer

 

FTIR Studies Data

The  spectrum  was  measured  in  the  solid  state  as  Potassium  bromide dispersion. The bands were recorded using the FT-IR technique. FT-IR spectral study revealed that similar characteristic peaks appear with minor differences, for the puredrug and drug formulation, as shown in below figure. Hence it was confirmed that no chemical interaction had taken place between the drug and the polymer used.

Table 10. FTIR data

Functional groups

Frequency of pure drug (cm-1)

Frequency of formulation (cm-1)

C-H Stretching vibrations of methyl and methylene groups

3030.5-2860

3051.49-2789.16

C-H strecteching vibrations of the methoxy group

2840

2843.17

C-O streteching vibrations of the aromatic ethers

2236

2235.57

Skeletal stretching vibrations of the benzene ring

1607,1518

1599,1518

Figure 3.  FT – IR spectra of pure Etoricoxib

 

 

Evaluation of rapid release core (RRCT) and press-coated tablets Of Etoricoxib

The below table shows the pre-compressional parameters of power blend. There was change in angle of repose from F1 to F9. Angle of repose increased from 24.0 ± 0.02 to 32.0 ± 0.03 respectively.

Bulk Density and Tapped Density of all formulations are shown in the table No: The results indicated that both densities ranges from 0.58 ± 0.02 to 0.68 ± 0.04 gm/c.c and 0.65 ± 0.03 to 0.79 ± 0.02 gm/c.c respectively.)

% Compressibility ranges from 9.2 ± 0.04 to 26.58 ± 0.03 and Hausner’s Ratio 1.10 ± 0.04 to 1.36 ± 0.04 respectively. All the formulations showed good and Fair flow properties.

Table 11. Pre-compressional parameters of power blend (F1 to F6)

Parameters

Formulation Code

F1

F2

F3

F4

F5

F6

Angle of repose

24.22 ±1.25

25.15±1.31

27.22 ±1.59

28.39 + 1.52

29.74 + 1.67

28.56 + 0.492

Bulk density (g/ml)

0.238 ±0.008

0.242 +0.009

0.028 +0.009

0.236+ 0.007

0.237 ± 0.006

0.2150 + 0.005

Tapped density  (g/ml)

0.263+ 0.010

0.277 +0.018

0.259 ±

0.014

0.267+ 0.012

0.265 ± 0.011

0.2484 + 0.018

Compressibility

Index (%)

9.54 ±0.71

12.63±1.78

11.71 ±  1.56

11.20 + 1.23

10.56 + 0.78

13.46 + 0.45

Hausner’s Ratio

1.21±0.01

1.19±0.01

1.23±0.02

1.22±0.01

1.17±0.02

1.18±0.01

Table 12.  Pre-compressional parameters of power blend (F7 to F10)

Parameters

Formulation Code

F7

F8

F9

F10

Angle of repose

21.20 ±0.261

22.44 ±0.380

26.76 ±0.311

26.42 ±0.144

 Bulk  density (g/ml)

 

0.46±0.02

 

0.45±0.02

 

0.49±0.00

 

0.44±0.01

Tapped

density (g/ml)

0.43±0.02

0.43±0.04

0.43±0.01

0.41±0.01

Compressibility

index (%)

16.04 ± 0.78

12.00 ± 0.70

314.29 ± 1.24

16.83 ±0.64

Hausner’s ratio

1.23±0.01

1.22±0.01

1.18±0.01

1.21±0.01

Post Compressional Parameters

Hardness: Table No shows hardness of all tablet formulations. hardness of all formulations was in between 3.5 to 5.5 kg/cm2

Percent Friability: Table   shows the friability values of all tablet formulations. The results indicated that the % friability of formulation was between 0.7% and 0.1% which is considered to be acceptable for withstanding normal shipping and handling.

Thickness: Table shows the thickness of all tablet formulations. The results indicated that the thickness of all formulations was between 3 – 3.7 mm. Thickness of all the tablets are almost same.

Weight variation test: Table  shows the % weight variation of all table formulations. The results indicated that average % weight variation of all tablets formulations was around 7%.

Disintegration Time: All the formulations showed disintegration time in the range of 2 min 40sec to 3 min 40 sec.

Table 13. Friability values of all tablet formulations

Physical  parameter

F 1

F 2

F 3

F  4

F 5

F 6

F 7

F 8

F 9

F 10

Weight variation

(%)

6.2

6.6

7.7

6.3

7.1

7.9

6.9

7.0

7.4

6.7

Hardness

(Kg/cm2)

3.6

4.2

5.2

4

4.5

5

3.4

3.9

4.5

5.5

Thickness

(mm)

3.3

3

2.9

3

3.2

3.7

3.1

3.0

3.5

3.7

Friability %

0.8

1

0.9

0.7

0.9

0.9

0.8

0.8

0.9

1

Disintegration time

3min

2min 52s

3mis

3min

3min 10se

3min 20s

2min 40s

2min 40s

2min30s

3min 40s

Table 14. Post compressional paramaeters of Press coated  tablets

Physical  parameters

P1F9

P2F9

P3F9

P4F9

P5F9

Weight variation (%)

4.5

4.6

4.0

3.9

4.4

Hardness (Kg/cm2)

7.2

6.8

7.0

6.9

7.1

Thickness (mm)

5.0

4.8

4.5

4.7

4.8

Friability %

0.8

0.9

0.9

0.7

0.9

From the above results it is eveident that the post compressional parameters are in acceptable limits.

In-vitro Release Studies

All the formulations were studied for 60 minutes, with time interval of 5 minutes. During this study among the 10 formulations F9 formulation showing fastest release (97%) with in 30 min. Based on the drug release F9 selected was optimized and further formulated for press coating.

Table 15. Dissolution studies of different formulations

Dissolution time (Min)

Core formulation

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

5

26

31

31

29

29

25

31

32

41

31

10

25

48

43

35

37

39

43

54

63

29

15

43

49

53

47

49

47

56

66

78

34

20

52

55

62

59

62

63

68

78

91

39

30

63

76

70

66

72

74

79

84

99

46

45

78

89

83

78

84

83

83

93

-

50

60

89

92

93

86

91

96

102

98

-

63

Figure 4. Dissolution study of f1, f2, f3

 

Figure 5. Formulations Dissolution f4, f5, f6

 

Figure 6. Formulations Dissolution f7, f8, f10

 

Figure 7. Formulations dissolution of f9

 

Based on the drug release with in the required time period F9 was optimizedand further formulated for press coating.

Table 16. Dissolution study of press coated tablets

Time in hrs

Press coat Formulation code

P1F9 (%)

P2F9

P3F9

P4F9

P5F9

1

6

6

3

3.8

2

2

11

8.2

9

7.7

5

3

14

10.6

21

31.1

10

4

18

13.7

39

39.6

14

5

23

34.6

60

52.3

20

6

36

48.8

79

71.6

32

7

48

88.3

87

89.4

47

8

75

99

92

95.2

59

Figure 8. Dissolution study of press coated tablets

 

From the above core formulations F9 was selected for press coat by using different  polymers(HPMC and E.C) in different ratios (4:0, 3:1, 2:2, 1:3, 0:4) among which 3parts of HPMC and 1 part of E.C was optimized based on the lag time (11

% with in 4 hours) and  percent of drug release and also further evaluated.

Stability Studies

Stability studies of the formulation F9 of press coated were carrried out to determine the effect of formulation additives on the stability of the drug and also to determine the physical stability of the formulation. The stability studies   were carried out at 25ᴼ C/60%RH, 30 ºC/65% RH and 40 ºC/75% RH for 90 days. There was no significant change in the physical property and percent of drug release during 10 hour during the stability period.

Table 17. Stability studies of the formulation

Sampling interval

 

% of drug release at

25°C/60%RH

30°C /65% RH

40°C /75% RH

O day

93

92.7

92.2

15 days

94.5

94.45

94.40

45 days

96.96

96.85

96.82

90 days

96.5

96.42

96.38

Conclusion

The dosage forms can be classified based on the drug release like immediate release and controlled release dosage forms among them the controlled release dosage forms are gaining importance because of many advantages offered by it. There are many routes of drug delivery like oral route, parenteral route etc among them oral route has many advantages like patient compliance, dose precision etc. The lag time can be achieved precisely by using press coated  tablets.Extensive literature survey has been performed to optimize, methods, mechanisms and benefits of the controlled release drugs.The various pre formulation studies like solubility; melting point of the drug has been performed in order to know the suitability of the drug for control release.The authencity of the drug was found out by performing FT IR studies and comparing to that of reference.The interaction studies were performed by FTIR, studies indicating there is no interaction between Etoricoxib, HPMC,E.C and other formulation excipients.The various pre compression parameters like angle of repose, bulk density, hausners ratio, compressibility index, porosity, and drug content were performed and all were shown satisfactory results.

Conflicts of Interests

All authors have none to declare

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