Glimepiride And Valdecoxib Combination Mucoadhesive Tablets Biology Essay

Widening the abode clip of a dose signifier at a peculiar site and commanding the release of drug from the dose signifier are utile particularly for accomplishing controlled plasma degree of the drug every bit good as bettering bioavailability. The aim of this survey was to widen the GI abode clip of the dose signifier and command the release of Glimepiride and Valdecoxib utilizing mucoadhesive tablet to accomplish controlled plasma degree of the drug which is particularly in diabetes mellitus patients with NSAIDs therapy. Direct compaction method was used to fix tablets. All the preparations were shown good pre compaction and station compaction parametric quantities. The optimized preparation was subjected to accelerated stableness surveies.

Keywords: Glimepiride, Valdecoxib, mucoadhesive tablet, rating.

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Introduction

Glimepiride is a second-generation sulfonylurea that can acutely take down the blood glucose degree in worlds by exciting the release of insulin from pancreas and is typically prescribed to handle type II Diabetes ( non-insulin dependant diabetes mellitus ) . The drug is selected as theoretical account for planing sustained release because of its short biological half life ( 3.4±0.7 hours ) necessitates that it can be administered 2 or 3 doses with 2.5 to 10 milligrams per twenty-four hours.

Valdecoxib, a non-steroidal anti-inflammatory drug ( NSAID ) that exhibits anti-inflammatory, analgetic and antipyretic belongingss was chosen as a exemplary drug due to its high first base on balls metamorphosis. It undergoes both P450 and non-P450 dependant ( glucuronidation ) metamorphosis. The mechanism of action is believed to be due to suppression of Prostaglandin synthesis chiefly through suppression of cyclooxygenase-2 ( COX-2 ) .

Mucoadhesive Glimepiride tablets were prepared by utilizing Sodium carboxy methyl cellulose ( SCMC ) and Hydroxy propyl methyl cellulose ( HPMC ) , carbopol and Poly vinyl pyrrolidone. There is no handiness of Glimepiride and Valdecoxib mucoadhessive tablets commercially. So an effort has been made to develop a combination sustained release mucoadhessive preparation of anti-diabetic drug with NSAID.

MATERIAL AND METHODS

Materials

Glimepiride and Valedicoxib were obtained from Dr. Reddy ‘s research labs, Hyderabad, India. HPMC K4M, Carbopol-934P, Povidone, Mg stearate were procured from SD all right chemicals, Mumbai, India and all other ingredients used were of analytical class.

experimental methods:

Pre preparation Studies for Drug Excipients Compatibility:

The pure drug and preparation ( F4 ) were individually assorted with IR grade K bromide in a ratio ( 1:100 ) and pellets were prepared by using 10 metric ton of force per unit area in hydraulic imperativeness. The pellets were so scanned over scope of 4000-400cm-1 in FTIR instrument.

Preparation of mucoadhesive Tablets:

Mucoadhesive tablets were prepared in 3 stairss

Step-I: Preparation of Core Layer ‘s Mixture:

Glimepiride, Valdecoxib, Hydroxy propyl Methyl Cellulose, Carbopol-940, Sodium Carboxy Methyl Cellulose-H, Polyvinyl Pyrrolidone-K30 and Magnesium stearate were assorted good by utilizing glass howitzer and stamp. This mixture was used for the readying of nucleus bed of the tablet. The composing of nucleus bed was represented in Table 1.

Step-II: Preparation of Backing Layer ‘s Granules:

Carbopol 934P, Poly vinyl pyrrolidone, Magnesium stearate, Saccharin Na were assorted good utilizing glass howitzer and stamp. In a separate glass beaker, solution of Amaranth was prepared utilizing ethyl alcohol as a dissolver. By bit by bit adding the colour solution to a dry mixture ; a wet mass/lump was prepared. Peppermint oil was added to this ball and assorted decently. Then this ball was passed through the screen ( Sieve No.40 ) . Then wet granules were dried in a Hot Air Oven at a temperature 500C for 20 proceedingss. To this dried granules, Mg stearate lubricator was added. These granules were used for the readying of endorsing bed of the tablet. The composing of endorsing bed was represented in table 2.

Step-III: Compaction:

For this intent an I.R. hydraulic imperativeness and Die Punch Set holding diameter of 10mm was used. First, the mixture of drug and polymers ( weighed quantity-150mg ) was compressed utilizing a force per unit area of 50kg/cm2 for 5 seconds. Then upper clout was removed and so granules of endorsing bed ( weighed measure -75mg ) were added over the first bed and compressed at a force per unit area of 200kg/cm2 for 15 seconds. By this manner, the bilayer tablet was prepared.

Evaluation OF TABLETS

Pre-compression parametric quantities

Compatibilities study

The compatibility of drugs and excipients used under experimental status were studied. The syudy was performed by taking 2 mg sample in 200 milligram KBr ( utilizing Perkin Elmer, spectrum-100, Japan ) . The scanning scope was 400 to 4000 cm-1 and the declaration was 1cm-1. This spectral analysis was employed to look into the compatibility of drugs with the excipients used.

Physical rating of tablets:

Thickness

The thickness of the tablets was determined utilizing a thickness prison guard gage ( Mitutoyo, New Delhi, India ) . Five tablets from each batch were used and mean values were calculated.

Uniformity of Weight Test

To analyze weight fluctuation, 20 tablets of each preparation were weighed utilizing an electronic balance ( Denver APX-100, Arvada, Colorado ) and the trial was performed harmonizing to the official method.

Hardness and Friability

For each preparation, the hardness and crumbliness of 10 tablets were determined utilizing the Monsanto hardness examiner ( Cadmach, Ahmedabad, India ) and the Roche friabilator ( Campbell Electronics, Mumbai, India ) , severally.

Swelling behaviour of matrix tablets

The extent of swelling was measured in footings of % weight addition by the tablet. The swelling behaviour of preparation GAP-1, GAP-2, GAP-3, GAP-4 and GAP-5 were studied. One tablet from each preparation was kept in a Petri dish incorporating phosphate pH 7.4. At the terminal of 2 hours, the tablet was withdrawn, maintain on tissue paper and weighed, repeated for every 2 hours till the terminal of 12 hours. The % weight addition by the tablet was calculated by eq.1.

S.I = { ( Mt-M0 ) / M0 } X 100 — — — ( 1 )

Where, S.I = Swelling Index, Mt = Weight of tablet at clip ‘t ‘ and

M0 = Weight of tablet at clip 0.

Uniformity in drug content:

The formulated tablets were tested for uniformity in Glimepiride and Valdecoxib contents by utilizing UV/ Visible spectrophotometer ( Elico SL 210 ) at 226 nanometers and 243 nanometer for Glimepiride and Valdecoxib severally.

Surface pH

The surface pH of the mucoadhesive tablets was determined in order to look into the possibility of any side effects in vivo. An acidic or alkalic pH may do annoyance to the mucous membrane. A combined glass electrode was used for this intent. The tablet was allowed to swell by maintaining it in contact with 1 milliliter of distilled H2O ( pH 6.5 ± 0.05 ) for 2hr at room temperature. The pH was measured by conveying the electrode in contact with the surface of the tablet and leting it to equilibrate for 1min.

Moisture soaking up surveies of mucoadhesive tablet

A 5 % w/v solution of Agar prepared in hot H2O and transferred into petri dishes and allowed to solidify. Five pre weighed tablets from each preparation were placed in vacuity oven overnight to take wet and laminated on one side with a H2O impermeable backup membrane. The tablets were placed on the surface of the agar and incubated at 37 & A ; deg ; C for one hr. Then the tablets were removed and weighed and the per centum of wet soaking up was calculated by utilizing combining weight. 2.

% Moisture soaking up = { ( concluding weight – initial weight ) /initial weight } x100 — — ( 2 )

Mucoadhesive Force Measurement

Mucoadhesive force measuring of tablets was done by modifying balance method. The right pan was replaced with a glass beaker container and on the left side beaker with a Cu wire. Teflon block of 1.5 centimeters diameter and 3 centimeter tallness was adhered strongly with the glass beaker. The two sides were so adjusted, so that the left manus side was precisely 5 g heavier than the right. Lodge the tummy on the Teflon block with aid of the cynoacrylate gum and make full the beaker with acidic buffer till the tissue remains in a damp status. Stick the tablet to beaker and set on the tissue for 15 proceedingss. After 15 proceedingss add H2O easy into right beaker until the tablet detaches.

Weigh the H2O required for the tablet withdrawal. Calculate Actual weight for withdrawal and force of adhesion in dynes by following eq.2.

Actual weight for withdrawal ( W ) = weight for withdrawal ( g ) ……………… . ( 2 )

Matrix Erosion

Each tablet weighed ( W1 ) were immersed in a phosphate buffer pH 6.8 for preset clip ( 1, 2, 4, 8 and 12 hours ) . After submergence, tablets were wiped off by the surplus of surface H2O by the usage of filter paper. The conceited tablets were dried at 60 & A ; deg ; C for 24 hours in an oven and maintain in a desiccator for 48 hours prior to be reweighed ( W2 ) . The matrix eroding was calculated utilizing the expression given in the eq.3.

( W1 – W2 )

Matrix Erosion = — — – – 100 ……… . ( 3 )

W1

Dissolution Surveies:

The disintegration of the mucoadhessive tablets were performed utilizing USP XXIII disintegration setup ( paddle method ) utilizing 500 milliliter of phosphate buffer ( pH 7.4 ) as the disintegration medium, which was maintained at 37±0.50C and stirred at 50 r.p.m. Tablet was glued with Cyanoacrylate adhesive ( Evobond ) from endorsing layer side to the glass slide and it was placed at the underside of jar of disintegration setup to avoid motion of tablet. Aliquots of 5ml of samples were withdrawn with a bulb pipette at different clip intervals of 30, 60, 120, 180, 240, 300 and 360 proceedingss and replaced with equal volume of phosphate buffer ( pH 7.4 ) at each backdown, filtered it through Whatmann Filter Paper No.1.

The samples were so analysed utilizing dual beam ultraviolet seeable spectrophotometer ( Elico SL 210 ) at 226 nanometers and 243 nanometer for Glimepiride and Valdecoxib severally. The cumulative sum of drug released at assorted clip intervals was calculated. This trial was done in triplicates.

Accelerated Stability Studies

To measure the drug and preparation stableness, stableness surveies were done harmonizing to ICH and WHO guidelines. Optimized preparation ( F4 ) was sealed in aluminium packaging coated inside with polythene, and so kept in stableness chamber maintained at 45 & A ; deg ; C and 75 % RH for 3 months. At the terminal of surveies, samples were analyzed for the drug content, in-vitro disintegration, drifting behaviour and other physicochemical parametric quantities

RESULTS AND DISCUSSIONS

Pre-compression parametric quantities

FTIR Spectrum:

Infrared Spectrum of Valdecoxib, Glimepiride and the preparation blend ( F4 ) were showed in Fig. 1, 2 and 3 severally. The uninterrupted characteristic extremums of Valdecoxib, Glimepiride were observed in the FTIR spectrum of the blend. This indicates the excipients used were non holding any negative interactions with the drugs used.

Post compaction parametric quantities

Thickness:

Tablets were evaluated for their thickness utilizing Vernier Callipers. The consequences are shown in Table 3.

Uniformity of Weight Test:

The tablets of all the preparations were passed the uniformity in weight test-IP. The consequences were shown in Table 3.

Hardness and Friability:

The hardness of formulated tablets was more than 5 kg/cm2 and the crumbliness was less than 1 % indicates the formulated tablets were found to hold good mechanical strength. The consequences were shown in Table 3.

Swelling behaviour of matrix tablets:

The swelling index of the formulated tablets was evaluated and the consequences were provided in Fig. 4. The values were 65.8, 71.8, 80.2, 86.5 and 85.9 % severally. The highest hydration ( swelling ) was observed with the preparation F4. The swelling index additions by increasing the contact clip as the polymers bit by bit absorbs the H2O due to hydrophilic nature with attendant puffiness.

Uniformity in drug content:

The values of Glimepiride and Valdecoxib content in the preparations was represented in Table 4.

Moisture soaking up surveies of mucoadhesive tablet

The values of Moisture soaking up of formulated tablets were shown in table 4.

Mucoadhesive strength Measurement:

The values of In-vitro mucoadhesive strength were shown in Table 4. The values were ranged from 14.52 ± 1.29 to 19.51 ± 2.25g. This indicates Hydroxy Propyl Methyl Cellulose, Carbopol-940, Sodium Carboxy Methyl Cellulose-H and Polyvinyl Pyrrolidone-K30 exhibited good mucoadhesive strength. Among assorted preparations, F4 was found to be best.

Surface pH:

The surface pH of formulated tablets were ranged from 6.11 ±2.25 to 6.99 ± 5.69 and represented in table 4.

Matrix Erosion:

The % matrix eroding of formulated tablets was ranged from 4.01±0.38 to 11.01±0.02 % and the values were represented in table 5.

Dissolution Surveies:

The secret plan consequence from in-vitro disintegration survey was shown in Fig. 5 and 6.

Accelerated Stability Studies

The optimized preparation ( F4 ) was tested for drug content, Surface pH, mucoadhesion strength and Swelling Index before and after accelerated stableness surveies. The survey proved that the preparations retain their characteristic parametric quantities before and after accelerated stableness surveies. The values were shown in table 6.

Table 1: composing of mucoadhesive tablets core bed

Ingredients ( milligram )

Formulations

F1

F2

F3

F4

F5

Glimepiride

2

2

2

2

2

Valdecoxib

20

20

20

20

20

Hydroxy Propyl Methyl Cellulose

5

10

15

20

25

Carbopol-940

10

20

30

40

50

Sodium Carboxy Methyl Cellulose-H

5

10

15

20

25

Polyvinyl Pyrrolidone-K30

2

4

6

8

10

Spray dried Lactose

102

80

58

36

14

Magnesium stearate

4

4

4

4

4

Entire Weight = 150 milligram

Table 2: Composition of mucoadhesive tablet endorsing bed

S. No

Ingredients

Quantity ( milligram )

1.

Magnesium stearate

30

2.

Carbopol-940

10

3.

Polyvinyl Pyrrolidone K30

25

4.

Amaranth

0.06

5.

Peppermint oil

5

6.

Saccharin Na

5

Entire Weight = 75 milligram

Table 3: Evaluation of physical parametric quantities of different mucoadhesive tablets

Formulation

Weight fluctuation trial

Thickness

( millimeter )

Friability ( % )

Hardness ( kg/cm2 )

n=5

Average Weight ( milligram )

IP Weight Variation Test

F1

499±1.28

Base on ballss

2.7±0.01

0.52±0.09

6.8±0.67

F2

498±2.27

Base on ballss

2.2±0.02

0.16±0.01

5.8±0.19

F3

500±3.59

Base on ballss

2.8±0.06

0.35±0.04

7.2±0.28

F4

501±5.68

Base on ballss

2.9±0.03

0.66±0.05

8.1±0.19

F5

498±4.55

Base on ballss

2.7±0.04

0.78±0.01

5.9±1.02

Table 4: Evaluation parametric quantities of different mucoadhesive tablets

Formulations

% Drug content

Surface

pH

% H2O soaking up

Mucoadhession strength ( g )

Glimepiride

Valdecoxib

F1

100.15±3.62

99.35±4.49

6.56 ± 6.62

45.25 ±2.20

15.26 ±0.12

F2

99.62±5.59

99.99±6.66

6.99 ± 5.69

52.33 ±2.25

16.29 ±2.25

F3

99.15±6.59

100.02±3.33

6.59 ± 1.29

45.28 ±4.35

14.52 ±1.29

F4

99.10±4.44

100.59±5.52

6.12 ± 1.55

56.29 ±3.26

19.51 ±2.25

F5

100.95±6.31

98.98±6.59

6.11 ± 2.25

49.28 ±2.25

15.54 ±1.25

Table 5: Matrix Erosion of formulated tablets

Formulation

% matrix eroding

2hour

4 hr

6 hr

8 hr

12 hr

F1

4.01±0.38

5.89±0.52

6.38±0.25

7.95±0.06

9.50±0.05

F2

5.25±0.16

6.12±0.21

7.15±0.06

8.16±0.05

9.95±0.06

F3

5.62±0.56

6.39±0.15

7.89±0.19

8.99±0.15

10.29±0.04

F4

4.69±0.06

6.22±0.54

7.80±0.52

9.25±0.25

10.23±0.02

F5

4.55±0.55

7.01±0.62

7.88±0.23

8.95±0.45

11.01±0.02

Table 6: Summary of parametric quantities before and after stableness surveies

Parameter

Before stableness surveies

After stableness surveies

Drug content ( % )

Glimepiride= 99.10

Glimepiride= 99.05

Valdecoxib= 100.59

Valdecoxib= 100.50

Surface pH

6.12

6.11

Mucoadhession strength ( g )

19.51

19.50

Swelling Index ( % )

86.5

86.5

Fig 1: Infra-Red Spectrum of Valdecoxib

Fig 2: i.r. Spectrum of Glimepiride

Fig 3: i.r. Spectrum of preparation blend

Fig.4: Swelling Index of formulated tablets

Fig.5: In-vitro drug release from formulated tablets ( Glimepiride )

Fig.6: In-vitro drug release from formulated tablets ( Valdecoxib )