Formulation and Evaluation of Mucoadhesive Buccal Tablets of Curcumin and its Bioavailability Study

 

Deepak Karki, Gururaj S. Kulkarni*, Shivakumar Swamy, Sheeba FR

Mallige College of Pharmacy, Bangalore-90

*Corresponding Author E-mail: Skguru2006@gmail.com

 

ABSTRACT:

Aim: The main objective of the present work is to improve the bioavailability of curcumin by buccal route and to study in-vitro and in-vivo drug release. Materials and Methods: The mucoadhesive buccal tablets were formulated by direct compression method using hydrophilic polymers such as guar gum, xanthan gum, HPMC E15 in different concentration and piperine as permeation enhancers (1%). Ethylcellulose is used as backing layer to promote the unidirectional flow of drug in the buccal region. Curcumin has a number of beneficial activities, such as potent antioxidant, anti-inflammatory, anticancer, anti-rheumatic and anti-diabetic. When Curcumin is administered orally it has low bioavailability because of poor absorption, rapid GIT metabolism and hepatic first pass metabolism. Curcumin has poor aqueous solubility and better lipid solubility, and buccal region consist of lipid, so the absorption of curcumin can be increased by this route. Results and Discussion: The FT-IR spectra of pure drug with different polymers showed no shift in peak, indicating absence of interaction. The prepared formulations were evaluated for pre-compression studies such as bulk density, tapped density, angle of repose. The post-compressions studies such as weight variation, thickness, friability, hardness, mucoadhesive strength, drug content, swelling studies, in-vitro diffusion studies and in-vitro dissolution studies. Conclusion: All the prepared formulations were within the standard Pharmacopoeial limit. The formulation (FX2) containing xanthan gum showed the best dissolution (97.75%) within 4.0 hours and it follows higuchi model. The in-vivo animal study showed the better bioavailability by buccal route when compare to oral route.

 

KEYWORDS: Curcumin, Xanthan gum, Guar gum, HPMC E15, Permeation enhancer, FTIR, Direct compression, unidirectional flow.

 


 

INTRODUCTION:

The administration of pharmaceutical dosages form by oral route is the most accessible and easy route to the patients when compare to other dosages form like parenteral for systemic availability of drugs but the administration of certain pharmaceutical dosage form by oral route have demerits like reduction in bioavailability of dosage form due to acidic degradation and enzymatic metabolism in stomach, degradation in alkaline pH and metabolism by liver.1

 

The mucoadhesive drug delivery may be defined as drug delivery systems, which utilizes the property of bioadhesion of certain hydrophilic polymer, which when hydrated become adhesive and can be used for extended period of time for targeting of drug to particulars region.2

From last few decades the interest has been increased for administrating the drug through buccal route for both local and systemic affect when compare to other transmucosal route such as sublingual, nasal, ocular, vaginal and rectal route. The unique character of buccal cavity is that the buccal mucosa is thin and has rich blood supply and lymphatic drainage that drain drug directly into the systemic circulation, which ensure reduction in absorption of drug by different pathway and lead to high bioavailability. In-case of toxicity, treatment can be terminated.3

 

Buccal tablets are small and flat, intended to be held in mouth between the cheek and gum or in cheek pouch, from where the drug content to be absorbed directly through oral mucosa. The buccal tablets may release the drug quickly or may be design to release it slowly for prolonged action, resulting better bioavailability of drugs due to preventing of first-pass metabolism, GIT degradation for GIT sensitive drugs and avoiding various enzymatic degradation. These tablets can be applied to different sites in the oral cavity, including the palate, mucosa lining, and the cheek or between the lip and the gum. Bioadhesive tablets are generally prepared by direct compression, but sometimes wet granulation methods are used; it required more compression pressure to produce a hard tablet. In order to achieve unidirectional release, multilayered tablets may be prepared by adding and compressing the ingredients layer by layer with a hydrophobic polymeric layer as a backing membrane.4

 

Curcumin is a lipophilic polyphenol compound extracted from the rhizome of curcuma longa family Zinigiberaceae and has wide spectrum of biological and pharmacological activities such as potent anti-oxidant, anti-inflammatory, anti-cancer, anti-rheumatic, anti-diabetic, hepatoprotective, anti-spasmodic, etc. However when curcumin is administered orally it has low bioavailability because of poor absorption, rapid GIT metabolism and hepatic first pass metabolism.5

 

Curcumin has poor hydrophilic solubility but better lipophilic solubility and buccal region is lipophilic in nature, so the absorption can be increase by this route. Further the curcumin in combination with piperine also improves the bioavailability of curcumin because piperine an alkaloid present in black pepper act as permeation enhancer.6,7

 

MATERIALS AND METHODS:

Materials:

Curcumin and Piperine was received as gift samples from Novel Nutrients (Abbigere, Bangalore). Guar gum, xanthan gum and HPMC E15 were purchase from Signet chemical corporation Pvt. Ltd. Others chemicals from Thermo Fisher Scientific, Mumbai. All the reagents and materials were of analytical or pharmacopoeial grade.

 

Methods:

Preformulation study of curcumin:8,9

Preformulation study is the first step in the development of dosage form of a drug Substance.

 

·      Solubility:

The solubility of Curcumin was tested in distilled water, methanol, chloroform and acetone.

 

·      Melting point:

Melting point of Curcumin was determined by open capillary method.

 

·      Determination of λmax:

100 mg of Curcumin was accurately weighed and dissolved in 100 ml of methanol in volumetric flask. Further the concentration was maintained to 10μg/ml and scanned for maximum absorbance in UV/Vis double beam spectrophotometer in the range from 800 to 400 nm, using methanol as blank.

 

·      Compatibility study:

A successful formulation depends on the careful selection of excipients to facilitate release of drug and also protect it from degradation. In the formulation drug and polymer may interact as they are in close contact with each other, which could lead to the instability of drug. Preformulation studies regarding the drug-polymer interaction are therefore very critical in selecting appropriate polymers. FT-IR spectroscopy was employed to ascertain the compatibility between Curcumin and the selected polymers.

 

Preparation of Curcumin mucoadhesive buccal tablets:10

The tablets were prepared using compositions as given in Table 1. All the ingredients were passed through sieve #80 and properly mixed together in an air tight plastic container. The mixed ingredients were evaluated for pre-compression parameters, followed by direct compression in multi tablet punching machine. The weight of the tablets were adjusted to 200mg and coated with ethyl cellulose 60 mg to maintain the unidirectional flow of drug.


 

 

Table 1: Formulation development of curcumin mucoadhesive buccal tablet

FORMULA CODE

FG1

FG2

FG3

FG4

FX1

FX2

FX3

FX4

FH1

FH2

FH3

FH4

Curcumin

100

100

100

100

100

100

100

100

100

100

100

100

Guar gum

10

20

30

40

-

-

-

-

-

-

-

-

Xanthan gum

-

-

-

-

10

20

30

40

-

-

-

-

HPMC E15

-

-

-

-

-

-

-

-

10

20

30

40

MCC

15

15

15

15

15

15

15

15

15

15

15

15

PEG-6000

11

11

11

11

11

11

11

11

11

11

11

11

Piperine

2

2

2

2

2

2

2

2

2

2

2

2

Magnesium stearate

3

3

3

3

3

3

3

3

3

3

3

3

Talc

2

2

2

2

2

2

2

2

2

2

2

2

Lactose

57

37

27

17

57

47

37

27

57

47

37

27

Ethyl cellulose

60

60

60

60

60

60

60

60

60

60

60

60

Total weight

260

260

260

260

260

260

260

260

260

260

260

260

*All  quantities are in milligrams (mg) only.                       * MCC= Micro crystalline cellulose

*PEG = Polyethylene glycol                                                  *HPMC= hydroxy propyl methyl cellulose.

 


POST-COMPRESSIONAL STUDIES:11, 12

·      Weight variation test:

According USP twenty tablets were selected randomly from each batch and weighed individually by using analytical weighing balance. The average and standard deviation were calculated.

 

·      Thickness:

The tablets thickness is important for uniformity of tablet size. Thickness was measured using Vernier Caliper. The average of three tablets was taken. The tablet thickness should be controlled within ± 5 variations of a standard value.

 

 

 

·      Hardness test:

The hardness of the tablet indicates the ability of a tablet to withstand mechanical shocks while handling. It is measured by using Monsanto hardness tester. It is expressed in kg/cm2. The average of six tablets was taken according to USP guidelines from each formulation.

 

·      Friability test:

It indicates the loss in weight of tablets in containers during transportation. Roche friabilator was used. 20 tablets were weighed and initial weight was recorded and place in Roche friabilator and rotates at 25 rpm for 4 minutes. The tablets were removed and again weighed, final weight was recorded. It is calculated by using the equation.

 

                    Initial weight of the tablets – Final weight of the tablets

% Friability =---------------------------------------------------------- X  100

                                    Initial weight of the tablets

 

·      Mucoadhesion strength:13

The mucoadhesive strength of tablet was measured in modified double beam physical balance by using goat buccal mucosal membrane. The apparatus consist of a double beam physical balance. The goat buccal mucosa was obtained from local slaughter house and store in pH 6.8 phosphate buffer. The experiment was performed within 2 hours of procurement of buccal mucosa. The goat buccal mucosa was fixed in a stainless steel piece with cyano acrylate adhesive in left pan and place in a beaker. Then pH 6.8 phosphate buffer was added into the beaker up to the upper surface of the porcine buccal mucosa to maintain buccal mucosal viability during the experiment. Then the tablet was attached to the upper clamp of the apparatus and the beaker was raised slowly to establish contact between porcine buccal mucosa and the tablet. The pan was left undisturbed for 10 minutes and slowly increases the weight on right pan till the curcumin mucoadhesive buccal tablet got detached from the goat buccal mucosa. The weight required to detach the buccal tablet was recorded.

 

·      Drug content:14

Five tablets from each formulation were taken, crushed and mixed. From the mixture 100mg equivalent of mixture was extracted thoroughly with in pH 6.8 phosphate buffer and 3% tween 80 (Tween 80 is use as a surfactant to enhance the solubility of curcumin).The amount of drug present in each extract was determined using UV/Vis spectrophotometer at 424.4nm against blank.

 

                             Absorbance   x 1 x Dilution factor

Percentage drug content = ----------------------------------------x 100%

                                        Slope x 1000 x Dose

 

·      Swelling studies:13

The curcumin mucoadhesive buccal tablets were weighed accurately (initial weight) and placed in a Petri dish containing 5ml of pH 6.8 phosphate buffer, temperature was maintained at 37±0.5oC. At the end of 3 hr the tablets were removed from the Petri dish and swollen tablets were reweighed (final weight). The swelling index was calculated according to the formula.

                                   Final weight – Initial weight

Swelling index (%) =---------------------------------- X 100

                                                      Initial weight

·      In-Vitro Retention time:13

It is determine by using goat buccal mucosa in modified magnetic stirrer apparatus. The goat buccal mucosa was attached to glass slide and the curcumin mucoadhesive buccal tablet was press on buccal mucosa for 30 seconds and immersed in beaker containing 500ml of pH 6.8 phosphate buffer, maintained the temperature at 37±0.5ºC. The magnetic beat was rotated at 25 rpm, the experiment was continuing till the buccal tablet detached from the goat buccal mucosa.

 

·      Dissolution Studies:14

The drug release studies from curcumin mucoadhesive buccal tablet were performed using USP II dissolution test apparatus (paddle type). The tablet was formulated in such a way that it release the drug from one side only, as it design for unidirectional release of drug from buccal cavity. Initially tablets were placed in 900ml of pH 6.8 phosphate buffer containing 3% tween 80 (tween 80 is use as a surfactant to increase the solubility of curcumin in water as curcumin is insoluble in water) and maintained the temperature at 37±0.5oC For 4.0 hours. The paddle was rotated at 100 rpm. 5ml was collected manually after every 30 min. Dissolution medium was replaced with same amount of fresh buffer to maintain the sink condition and analyzed for drug content after suitable dilution with respective medium, using a UV-Visible Spectrophotometer at 424.4nm.

 

·      Ex-Vivo Diffusion study:14

The Ex-vivo diffusion study was done in both side open ended glass cylindered. One end was tie with goat buccal mucosa and placed in 250ml beaker containing 100ml of pH 6.8 phosphate buffer and 3% tween 80. The whole setup was kept in magnetic stirrer and maintained the temperature at 37±0.5oC.

 

The rotation was maintained at 100 rpm. The 2ml of sample was withdrawn at every 30 minutes and fresh medium was added to maintain the sink condition. The absorbance was measure at 424.4 nm using UV/Vis Spectrophotometer.

 

·      In-vivo study:15,16

Three healthy albino rabbits weighing about 1.5 to 2.5 kg were selected, marked and fasted for overnight. All the animals were administered with the oral dose of curcumin as a standard drug and the time was noted. Then 0.5 ml of blood was withdrawn from the marginal ear vein at an interval of 0, 1, 2, 4, 8 and 16 hours.

 

The serum was separated and curcumin was estimated by using HPLC. After the washout period of 7 days again the same rabbits were administered with prepared curcumin mucoadhesive formulation. Rabbits were anaesthetized (Ketamine hydrochloride) and the curcumin mucoadhesive buccal tablet (1.42mg/kg) was fixed in the buccal position of the oral cavity and the time was noted. Then 0.5 ml of blood was withdrawn from the marginal ear vein at an interval of 0, 1, 2, 4, 8 and 16 hours. The serum was separated and the serum concentration of curcumin in blood was measured by HPLC method. In this method, the estimation of curcumin was carried out using a reversed phase C18 column, mobile phase (methanol and Acetonitrile). The flow rate was maintained at 0.8ml/min and wavelength was set at 430 nm.

 

RESULT AND DISCUSSION:

Determination of solubility:

Table 2: solubility of curcumin

Distilled Water

Insoluble

Acetone

1mg/ml

Chloroform

1mg/ml

Methanol

10/ml

 

Determination of melting point:

The melting point of curcumin was found to be 183ºC

 

Determination of λ max of Curcumin:

The λ max of the Curcumin was found to be 424.4nm in methanol.

 

Standard Calibration Curve for Curcumin

 

Graph 1: Calibration Curve of Curcumin at 424.4nm

 

The regression co-efficient of Curcumin was found to be 0.999 and the slope value was found to be 0.1383, which showed linearity between absorbance and concentration.

 

FTIR Compatibility study:

The compatibility studies of drug and polymers were done by FTIR. All the characteristic peaks of Curcumin were present in the spectrum of drug and polymer mixture, indicating compatibility between drug and polymer as shown in table 3.

 

Figure 1: FT-IR spectrum of curcumin

 

Figure 2: FT-IR spectrum of curcumin + guar gum

 

Figure 3: FT-IR spectrum curcumin + Xanthan gum

 

 

Figure 4: FT-IR spectrum of curcumin + HPMC E15

 


 

Figure 5: FT-IR spectrum of formulation FX2

 

 


Table 3: FT-IR Characteristic peak of Pure drug (Curcumin) and Drug with Polymers

Functional

Group

IR  Range

(cm-1)

IR Observed Peaks

Curcumin

Curcumin + guar gum

Curcumin + xanthan gum

Curcumin + HPMC

Formulation FX2

OH

3700-3400

3513.67

3513.67

3513.67

3512.7

3509.81

C-H

3000-2650

2850.27

2850.27

2844.49

2854.13

2848.35

C=O

1750-1550

1628.59

1634.38

1628.59

1630.52

1636.8

C=C

1540-1380

1507.1

1507.1

1509.03

1491.67

1470.46

C-O-C

1340-1150

1282.43

1282.43

1254.47

1253.5

1276.65

 

 

Pre-Compression evaluation of formulated mucoadhesive buccal tablet of Curcumin:

Table 4: Pre-compression parameters

Code

Bulk density (gm/cm3)

Tapped density (gm/cm3)

Carr’s index%

Haunser’s ratio

Angle of repose (°)

FG1

0.567±0.012

0.732±0.064

22.454

1.289

26.000±0.703

FG2

0.547±0.015

0.679±0.035

19.358

1.240

29.136±0.366

FG3

0.544±0.019

0.682±0.062

20.153

1.252

26.860±0.808

FG4

0.538±0.024

0.684±0.077

21.331

1.271

22.013±0.983

FX1

0.571±0.021

0.742±0.038

23.045

1.299

27.500±0.196

FX2

0.569±0.024

0.733±0.072

22.373

1.288

24.706±1.357

FX3

0.523±0.022

0.676±0.056

22.633

1.292

24.260±0.980

FX4

0.492±0.018

0.608±0.019

19.078

1.235

23.720±0.168

FH1

0.541±0.005

0.642±0.024

15.732

1.207

31.230±1.143

FH2

0.531±0.014

0.653±0.030

18.683

1.229

29.273±0.671

FH3

0.532±0.021

0.668±0.030

20.359

1.255

29.113±1.183

FH4

0.510±0.018

0.658±0.018

22.511

1.290

27.513±1.072


Pre-Compression Parameters:

Pre-compression parameters play an important role in improving the flow properties of pharmaceuticals especially in tablet formulation. These include Bulk density, Tapped density, Carr’s index, Haunser’s ratio and Angle of repose. Before formulation of tablets the drug were evaluated for all the above parameters and it was found that all the observations were within the prescribed limits of IP as shown in table 4. Bulk density of all the formulations was found to be ranging from (0.492±0.018-0.571±0.021)gm/cm3, tapped density was between (0.608±0.019-0.742±0.038) gm/cm3and angle of repose was found to be between (22.013±0.983 to 31.230±1.143) gm/cm3. Carr’s index was found to be between (15.732 to 23.045) and Hausner’s ratio was found to be between (1.207 to 1.299).

 

Post-Compression Evaluation of formulated mucoadhesive buccal tablet of Curcumin:

Weight Variation:

The weight of the tablets was found to between 379.88 ± 0.287 mg to 380.86 ± 1.096 mg as showed in table 5. Hence, weight variation test for all batches was within the standard pharmacopoeia limits of ±7.5% of the weight.

 

Thickness:

The thickness of tablets of each batch ranged between 3.8±0.022 to 3.9±0.019 mm (Table 5). This ensures good handling characteristics for all batches.

 

Hardness:

The hardness of tablets of each batch ranged between 4.0±0.103 to 5.0±0.196 kg/cm2 (Table No.5). This ensures good mechanical strength for all batches.

 

 

 

Friability:

The friability of all the formulated tablets was found to be between 0.44 ± 0.002 to 0.90 ± 0.042% as showing table 5. All the formulated tablets showed the % friability within the official limits, i.e. not more than 1%.

 

Drug Content:

All the formulated mucoadhesive buccal tablets were evaluated for uniformity drug content and it was found to be between 94.73±0.556 to 97.75±0.795% as shown in table 3.

 

Swelling index:

The swelling index of buccal tablets was found to be between 8.78±0.874 to 53.70±0.854 at the end of 3 hours as showed in table 5.

 

Mucoadhesive strength:

The mucoadhesive strength of buccal tablets was found to be between 8.34±0.763 to 10.83±0.763 which is good mucoadhesive strength as shown in table 3.

 

In-vitro Residence time:

The In-vitro residence time of buccal tablets was found to be between 150 minutes to 240 minutes which is considered as good retention time as shown in table 5.

 

In-vitro drug release:

As there is no specific dissolution test available for curcumin mucoadhesive buccal tablets. The curcumin mucoadhesive buccal tablet dissolution rate was studied as per IP specifications for conventional tablets with little modification. The best drug release of 97.75±0.89% was showed by formulation FX2. In-vitro release studies showed that formulation containing Xanthan gum showed the best release of drug within 4.0 hours.

 


 

 

Table 5: Post-compression parameters

Code

Thickness (mm)

Hardness (kg/cm2)

Friability (%)

Weight variation (mg)

Drug content (%)

Swelling index

Mucoadhesive strength (gm)

Retention time (min)

FG1

3.9±0.019

4.0±0.130

0.55±0.011

380.33±1.258

97.14±1.332

20.66±0.641

9.34±0.577

150

FG2

3.8±0.041

4.0±0.103

0.45±0.012

380.50±1.322

96.24±1.390

28.90±0.521

9.17±0.763

150

FG3

3.8±0.059

4.0±0.123

0.54±0.014

380.34±0.577

96.00±1.410

36.84±0.632

8.67±0.577

180

FG4

3.8±0.063

5.0±0.181

0.74±0.013

380.50±0.500

96.11±1.782

47.66±0.236

9.67±0.288

240

FX1

3.8±0.026

5.0±0.130

0.56±0.001

379.88±0.287

95.00±0.272

24.78±0.782

9.08±1.010

180

FX2

3.9±0.015

5.0±0.194

0.44±0.002

380.65±0.310

97.75±0.795

32.01±0.623

9.34±0.577

240

FX3

3.8±0.035

4.0±0.136

0.57±0.013

380.86±1.096

95.99±1.638

46.32±0.245

8.34±0.763

210

FX4

3.8±0.059

5.0±0.178

0.69±0.071

379.96±1.050

96.71±1.587

53.70±0.854

9.50±0.500

240

FH1

3.8±0.048

5.0±0.083

0.74±0.021

380.33±0.577

95.53±0.504

10.56±0.562

8.83±0.763

210

FH2

3.8±0.061

5.0±0.120

0.69±0.017

379.93±0.115

96.00±0.950

8.78±0.874

10.50±0.500

180

FH3

3.8±0.022

5.0±0.158

0.78±0.092

380.33±1.258

94.73±0.556

13.23±0.241

10.00±0.901

210

FH4

3.8±0.064

5.0±0.196

0.90±0.042

379.96±1.050

95.91±0.615

11.23±0.854

10.83±0.763

210

 

 

 

Table 6: In-vitro drug release studies of Curcumin mucoadhesive buccal tablet (FG1 –FX2)

SL. No

Time (min)

Cumulative % drug release

FG1

FG2

FG3

FG4

FX1

FX2

1

0

0

0

0

0

0

0

2

30

25.72±0.92

26.53±0.64

11.07±0.29

19.21±0.12

15.630±0.38

14.17±0.64

3

60

64.00±0.67

38.35±0.55

24.94±0.87

23.01±0.25

50.950±0.87

32.69±0.81

4

90

72.42±0.37

49.08±0.01

29.52±0.19

32.84±0.14

65.87±0.19

47.67±0.73

5

120

96.67±0.19

65.14±0.06

59.95±0.45

38.29±0.16

78.08±0.45

69.65±0.69

6

150

-

81.79±0.62

65.21±0.65

44.58±0.38

82.29±0.65

71.68±0.65

7

180

-

93.91±0.95

71.82±0.55

49.60±0.65

95.24±0.56

91.81±0.21

8

210

-

-

78.13±0.37

56.28±0.75

-

92.80±0.37

9

240

-

-

80.86±0.19

62.35±0.81

-

97.75±0.89

 

Graph 02: Cumulative % drug release of FG1 to FX2

 

Table 7: In-vitro drug release studies of Curcumin mucoadhesive buccal tablet (FX3 –FH4)

SL. No

Time (min)

Cumulative % drug release

FX3

FX4

FH1

FH2

FH3

FH4

1

0

0

0

0

0

0

0

2

30

25.23±0.52

15.14±0.52

11.07±0.13

4.572±0.58

3.10±0.56

3.10±0.68

3

60

30.12±0.95

24.80±0.18

16.88±0.25

12.41±0.36

9.21±0.42

6.81±0.82

4

90

37.69±0.81

29.05±0.94

21.58±0.52

19.72±0.26

15.57±0.36

13.59±0.35

5

120

45.63±0.68

35.95±0.71

29.27±0.84

24.92±0.58

19.61±0.25

14.16±0.58

6

150

56.57±0.18

45.03±0.61

32.39±0032

27.36±0.59

23.17±0.31

19.67±0.42

7

180

64.11±0.75

51.20±0.29

38.32±0.35

33.11±0.71

25.11±0.62

20.76±0.61

8

210

71.86±0.89

59.87±0.37

44.78±0.42

35.26±0.62

26.39±0.41

22.52±0.41

9

240

79.82±0.68

64.47±0.68

49.30±0.60

41.04±0.44

28.18±0.0.61

24.12±0.37

 


 

Graph 03: Cumulative % drug release of FX3 to FH4

 

Ex-vivo diffusion study:

The ex-vivo diffusion study of curcumin mucoadhesive buccal tablet was done for the best formulation FX2. The percentage drug release was found to be 89.86±1.132% at the end of 270 minutes as shown in table 8.

 

Table 8: Ex-vivo diffusion study on goat buccal mucosa

Time (min)

% of Drug Release

0

0

30

13.04±2.426

60

20.29±2.652

90

30.43±1.845

120

40.58±1.341

150

57.25±2.256

180

71.01±2.413

210

81.16±2.512

240

85.51±1.236

270

89.86±1.132

Graph No.04: Diffusion study of curcumin mucoadhesive buccal tablet

 

In-vivo study:

The in-vivo study of curcumin mucoadhesive buccal tablet was performed for the best formulation FX2. The Cmax was found to be 0.049μg/ml from oral route and 0.098μg/ml from buccal route as shown in table 9.

 

Table 9: Data showing the pharmacokinetic parameters of Curcumin by oral and buccal route.

Pharmaceutical Parameters

Curcumin (1.42 mg/kg)

 

Oral route

Buccal route

Cmax (μg/ml)

0.049

0.098

Tmax (hrs)

2.0

4.0

AUC (μg/ml/hr)

1.560

3.693

AUMC (μg/ml/hr)

3.978

8.897

T1/2

1.89

3.27

MRT (hr)

18.021

20.045

 

Drug Release Kinetic:

The data obtained from in-vitro dissolution studies were fitted in different models viz. zero order, first order, Higuchi and Korsmeyer- Peppa’s equation, the result were shown in table 8.It was observed that the highest correlation of best formulation FX2 was found for Higuchi model (R2=0.9597), which indicates the drug release would be by diffusion process.

 

Table 10: Mathematical modelling and drug release

Formulation Code

KINETIC MODULES

Zero order

Higuchi’s

Korsmeyer-Peppa’s

First Order

R2

R2

R2

R2

FG1

0.9409

0.9634

0.9512

0.8598

FG2

0.9691

0.9919

0.9826

0.9614

FG3

0.9100

0.9607

0.9532

0.9808

FG4

0.8867

0.7425

0.4913

0.6192

FX1

0.9173

0.9557

0.9861

0.0551

FX2

0.9584

0.9597

0.7370

0.0693

FX3

0.896

0.9901

0.9815

0.7783

FX4

0.9839

0.9626

0.9977

0.1307

FH1

0.9880

0.9085

0.9986

0.1890

FH2

0.9806

0.9453

0.9577

0.2102

FH3

0.9463

0.9454

0.9232

0.2414

FH4

0.9584

0.9380

0.9239

0.2512

 

Stability Study:

The stability studies for best formulations FX2 was carried out for 90 days at 40 ± 2 °C /75% ± 5% RH. There was no significant change in colour and odour, hardness, drug content and %CDR. 90 days of stability studies revealed that; there was no any significant degradation of the drug. The results found to be satisfactory.

 

CONCLUSION:

The mucoadhesive buccal tablets of Curcumin were prepared by direct compression method using various hydrophilic polymers such as guar gum, Xanthan gum, HPMC E15 and ethylcellulose is used as backing layer for maintaining the unidirectional flow of drug. The formulation FX2 containing Xanthan gum showed the 97.75±0.89 % of drug release within 4 hours so it is consider as best formulation. The optimized formulation (FX2) was subject for ex-vivo diffusion study and the percentage release of drug was found to be 89.86±1.132 % within 270 minutes. Then in-vivo study was performed using 3 albino rabbits for 24 hours and the bioavailability of curcumin was found to be increased by buccal route when compared to oral route.

 

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Received on 23.05.2017          Modified on 11.07.2017

Accepted on 10.08.2017        © RJPT All right reserved

Research J. Pharm. and Tech 2017; 10(12): 4121-4128.

DOI: 10.5958/0974-360X.2017.00750.8