chapter3. formulations and invitro evaluation of...

CHAPTER3. FORMULATIONS AND INVITRO EVALUATION OF MATRIX

TYPE TRANSDERMAL PATCHES OF INDOMETHACIN USING POLY MERS

HPMC E5 AND ETHYL CELLULOSE

Experimental Work

3.1. Characterization of Indomethacin

3.1.1. Organoleptic Properties

The drug powder was analyzed for colour and odour [Martin A, 2006].

3.1.2. Description

The drug sample (Indomethacin) was analyzed for physical appearance

and powder nature [Martin A, 2006] .

3.1.3. Melting Point

It determined by open capillary method. The lesser amount of

contamination can identified by this method and maintains excellent sign

of purity of sample [Martin A, 2006] .

3.1.4. Spectroscopic studies

A. IR spectrum interpretation

The infrared spectrum of the pure Indomethacin sample was recorded and

the spectral analysis was done. The dry sample of drug was directly

placed after mixing and triturating with dry potassium bromide.

B. UV spectroscopy

I. Determination of λmax

A drug of 0.0025%w/v solution is prepared by dissolving drug in methanol:

phosphate buffer solution and UV spectrum was verification between

wave length 200 to 400 nm [Busetti Cesare et al 1997].

II. Preparation of calibration curve for Indomethac in

Concentration was made using the phosphates buffers pH 7.4 media. It

analyzed spectrophotometrically through measuring absorbance at 320

nm wavelength. The absorbance values as shown in the table no.3.2. The

figure no.3.9: Shown standard calibration curves with slope 0.017 and

regression value of 0.995. The curve showed linear between 5 to 45ug/ml

at 320 nm. Drug solution with concentration of 100ug/ml was prepared.

Serial dilutions of 5,10,15,20,25,30,35,40,45,ug/ml drug.

3.1.5. Solubility Analysis

The drug sample was taken in a 5 ml of the solvent system. Stir it for 30

minutes. Keep it on a shaker for 48 hrs to achieve equilibrium and

centrifuge it for 10 minutes, the supernatant layer is then filtered out. The

dilutions are made from 5-45 µg /ml and the solubility is determined by

measuring the UV absorption [Martin A, 2009] .

3.1.6. Drug excipients interaction study

The compatibility of drug and polymers under experimental conditions is

important prerequisite before formulation. It essential to verify that the

drug does not react with the polymer and excipients in process condition

and not affecting the shelf-life of product or any other unwanted effects on

the formulation. The mixture of drug & polymers were used for

determination of Infrared spectrums.

A. FTIR Spectra of Indomethacin

Figure No.3.1: FTIR Spectra of Indomethacin

B. FTIR of mixture of Indomethacin and Ethyl cellul ose

Figure No. 3.2: FTIR Spectra of Indomethacin and Et hyl cellulose

C. FTIR of mixture of Indomethacin and HPMC E5

Figure No.3.3: FTIR Spectra of Indomethacin and HPM C E5

D. FTIR of mixture of Indomethacin, Ethyl cellulose and HPMC E5

Figure.No.3.4: FTIR Spectra of Indomethacin Ethyl c ellulose & HPMC E5

3.2. Formulation of Indomethacin Matrix Type Transd ermal Patches

Matrix type Transdermal film containing Indomethacin was formulated with

various ratios of HPMC E5 along with EC (10 cps). The polymers were

weight in requisite ratio and dissolve in Methanol: Dichloromethane.

Plasticizer and penetration enhancer use as a Dibutyl phthalate and

Dimethyl sulfoxide. Indomethacin mixed with polymers solution to formed

homogeneous dispersion and slowly stirred by magnetic stirrer. Then

Homogeneous dispersion poured into glass ring of 7.44 cm2 area (2.88cm

diameter) placed on Petri dish contain mercury. At ambient condition such as

Temperature 320C, RH 45% solvent was evaporated then over the Petri dish

kept inverted funnel. Finally, prepared film was store in desiccators [Shankar

M.S et al., 2010 and Rakesh P.et al., 2009] .

Table No.3.1: Composition of Indomethacin Transderm al patches

Batch

No.

Drug

(mg)

Polymer

weight(mg)

Plasticizer

DBP (%)

Penetration

enhancer

DMSO (%)

Solvent

(M:DCM)

(1:1)

(ml)

Ethyl

cellulose

HPMC

E5

F1

75

300

0

20

20

4

F2

75

00

300

20

20

4

F3

75

270

30

20

20

4

F4

75

240

60

20

20

4

F5

75

210

90

20

20

4

F6

75

180

120

20

20

4

F7

75

150

150

20

20

4

F8

75

120

180

20

20

4

F9

75

90

210

20

20

4

F10

75

60

240

20

20

4

F11

75

30

270

20

20

4

HPMC E5: Hydroxy propyl methyl cellulose E5 * DBP: Dibutyl phthalate

*DMSO: Dimethyl sulfoxide *M: Methanol *DCM: Dichlo romethane * DBP 20

% w/w and DMSO polymeric wt.

3.3. Evaluation of Indomethacin Transdermal Patches

3.3.1. Physical appearance

The formulated films were examined for colour, clearness, softness and

elasticity.

3.3.2. Thickness

It was précised by digital Vernier calipers. Three reading were taken for

standard deviation after thickness measured at five various site of patch.

[Shankar M.S et al., 2010]

Figure No. 3.5: Digital vernier caliper

3.3.3. Weight variation Test

Firstly, the three patches were chosen randomly from all batches then

three films were chosen and weighed separately from individual

formulation and calculated the mean for weight variation test and standard

weight was estimated[Verma P.R.P. et al., 2000].

3.3.4. Folding Endurance

It was calculated physically for formulated patches. The patches were cut

and constantly fold over at similar position till it broken. Numbers of time

the patch could be fold over at similar position without broken or cracked

given the value of Folding Endurance [Rakesh P.et al., 2009] .

3.3.5. Flatness

The films were cut from formulated patches longitudinally and lengths of

individual films were calculated. The difference in length due to no

evenness in flatness was measured. It was estimated through measured

constraint of films and zero percent constraint was considers to be equals

to a hundred percent flatness [Biswajit M et al., 2005] .

Constriction (%) = L 1-L 2 × 100

L 2

Where

L1:- Initial lengths of film

L2:- Final lengths of film

3.3.6. Percentage Moisture Absorptions

It was perform to ensure integrity and physical stability of patches at

elevated moist condition. It was performed at room temperature. The

patch was weight correctly then kept in desiccators contained hundred ml

of potassium chloride saturated solution maintains 80-90% Relative

humidity. The patch was withdrawn and reweighed, after 3 days. The

percent Moisture absorptions were determined to use followed Formula

[Garala K. C. et al., 2009] .

% moisture absorption = (Final weight – Initial weight) X 100

Initial weight

3.3.7. Percent Moisture loss

It was perform to ensure physical stability and moisture sensitiveness

during storage of patch. This test performed as followed. The patch was

weigh correctly then placed in desiccators contained calcium chloride in

anhydrous form. The patch was withdrawn and reweighed, after 3 days. It

was determined to use followed Formula [Garala K. C. et al., 2009] :

% moisture loss = (Initial weight - Final weight) x 100

Final weight

3.3.8. Water vapour transmission rate

The 5ml vial was cleaned and dried. The vial contained Fused Cacl2 and

polymers film of 4 cm2 was set above edge by adhesives tape. Then vial

was weight and kept for stability at 80-90 % Relative humidity conditions

for 7 days until it show constant weight gain. The vial was withdrawn and

reweighed at regularly interval for 24hrs [Carmelo Pet al., 2008] .

Transmission rate = 100 x (Final weight - Initial weight) / Area x Time

3.3.9. Tensile Strength

It was measured with the apparatus designed as followed. The instrument

was designed such that it had horizontal wooden platform with fixed scale

and attachments for two clips that holds transdermal patch under test. Out

of the two clips one was fixed and other was movable. The weights were

hanged to one end of pulley and the other end of pulley was attached with

movable clip and The wooden platform was such fitted that it would

not dislocate while the test is running. The three strips of patch were

cut having 2cm length and 1cm breadth. The thickness and breadth of

strips were noted at three sites and average value was taken for

calculation. Weight was slowly put in pot to increases the dragging power

until films were broken [Carmelo Pet al., 2008] .

Figure No.3.6: Assembly for percent elongation

The tensile strength was calculated by using following formula.

Where,

m- Mass in kg.

g- Acceleration due to gravity.

b- Breath of specimen.

t – Thickness of specimen.

3.3.10. Percent elongation

It was measured with followed formula [Carmelo Pet al., 2008] .

Where,

L = length after force was applied

L0 = original length

3.3.11. Drug content determination

2 The patch at 3.14 cm was incised then put in container contained 100ml

of Phosphates buffer solutions of pH 7.4 and The solutions were stirred

through a Teflon’s covered magnetic bed for 24 hrs then solutions were

pass through a filtered and examined on spectrophotometer at 320nm with

proper dilution [Biswajit M et al., 2005] .

3.3.12. Invitro Drug Diffusion Studies of Matrix Ty pe Transdermal Patches

of Indomethacin

A. Preparation of skin

It removed from dorsal-site of dead rat and it washed with water. The skin

was kept in normal saline solution in refrigerator until skin was used for

diffusion study. Prior to used, it allowed equilibrating with room-

temperature. Then skin was climb linking donors along with receptor

compartments of cell. It clamped a manner dermal part will be in contact

with receptor medium.

B. Diffusion Cell

The drug-diffusion study was carried out to recognize the penetration

mechanism of drugs from membrane of the Trans-dermal systems. In

present study, Franz diffusion-cell (volume- 50ml) is employed. The

Diffusion-cells usually consist 2-compartment, first contains the drug

Compartment (donor-compartment) and another contains diffusion media

(receptor-compartment) divided with membrane (rat abdominal-skin) cells

consisting sampling-port & heat regulating sheath. Its inlet and outlets

were linked by latex-tube consequently the sheath has stagnant-water

within and heated with the help of hot-plate. Taflon coated magnetic bead

was utilized for stirring the receptor-solution in magnetic-stirrer. The

excised rat abdomen skin was positioned on receptor-compartment and

both compartment clutched tightly by clamp. Phosphate-buffer pH-7.4 was

employed as receiving fluid. The 37± 0.5°C temperature was regulated

using hot plate. Diffusion-study was investigated for 24hrs and 0.5ml

samples were taken at intervals of 1hr. Equal volumes of phosphate-buffer

pH-7.4 were replaced in receptor-compartment to keep sink-condition and

the sample was examined at 320 nm [Gye J.R et al., 1999 and Dey S.

Malgope et al., 2010] .

Figure No.3.7: Franz diffusion cell

3.4. Stability studies of Indomethacin transdermal patches

The stability of drug has to main condition in estimating their acceptance

or rejection.

Reasons for Stability-Studies:

� It might be chemicals degradations of active ingredient important to a

considerable lesser the amount of beneficial agents in the dosage-form.

� The chemical degradation of drugs could not be wide; the poisonous product

might be produced in the decay procedure.

� Instability of drugs might be to reduce it bio-availability. This can lead to

considerable lesser in the beneficial efficiency of the dosage-form.

During the stability-studies products are exposing at normal condition of

heat and moisture. How-ever the study takes an extended period; thus it will

be suitable to perform accelerates stability-studies where the products are

store below excessive condition of heat. In the present work, stability-Study

was performed on chosen batch. The patches were stored at temp 400C ±

20C & RH 75 ± 5% for duration of six month. After an interval of sixty days

each sample was withdrawn and tested for drug diffusion [Kulkarni M S et

al., 2005] .

3.5. RESULT AND DISCUSSION

Characterization of Indomethacin

3.5.1. Organoleptic properties

Taste of the drug was found to be bitter.

3.5.2. Description

Visual inspection showed that Indomethacin is pale yellow in colour, and

odorless.

3.5.3. Melting point

The literature value is in the range of 1580c-1620c. Indomethacin Melting-

point was found to be 157.80C.

3.5.4. Spectroscopic studies

a) UV spectroscopy

Figure No.3.8: Absorption spectrum of Indomethacin

A. Standard Calibration Curve of Indomethacin

The drug solution of with concentration of 100ug/ml was prepared. Serial

dilutions of 5, 10, 15, 20, 25, 30, 35, 40, 45 ug/ml drug concentrations were made

using the phosphate-buffer pH-7.4media. It was examined spectrophotometrically

with measuring the absorbance at 320 nm wavelength. The absorbance values

as shown in the table3. The figure shows standard calibration curves with slope

0.017 and regression value of 0.995. The curve has shown linear between 5 to

45ug/ml at 320nm.

Table No.3.2: Standard Calibration Curve of Indomet hacin at pH 7.4

Sr. No

Concentration

of drug in ug/ml

Absorbance

1.

0

00.00

2.

5

00.092

3.

10

00.192

4.

15

00.237

5.

20

00.362

6.

25

00.458

7.

30

00.544

8.

35

00.650

9.

40

00.710

10.

45

00.776

Abs

orba

nce

Standard calibration curve of Indomethacin

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

Standard calibration curve of Indomethacin

Linear (Standard calibration curve of Indomethacin)

0.1

0

0 10 20 30 40 50

Concentration ug/ml

Figure No.3.9: Standard Calibration Curve of Indome thacin

3.5.5. Solubility of Indomethacin

Table No.3.3: Solubility profile of Indomethacin

Sr. No.

Solvent

Solubility

1

Distilled water

Insoluble

2

Methanol

Soluble

3

Chloroform

Soluble

4

Phosphate buffer

Slightly soluble

3.6. EVALUATION OF INDOMETHACIN TRANSDERMAL PATCHES

3.6.1. Thickness

The thickness of Indomethacin patches were between 247.81 ± 6.89 to

259.15 ± 5.93µm.

Table No.3.4

Thickness Indomethacin patches of batch F1 to F11

Formulation Thickness ( µm)

F1

250.71 ± 3.21

F2

253.18 ± 5.32

F3 259.15 ± 5.93

F4

249.31 ± 7.31

F5

247.81 ± 6.89

F6

254.41 ± 5.92

F7

256.38± 5.85

F8

249.00 ± 4.76

F9

251.00 ± 3.66

F10

256.33 ± 4.61

F11

253.45 ± 4.14

All the values represent mean ± S.D. (n=3)

3.6.2. % Elongation

% Elongation was between 40.46 to 72.43this shows uniformity in

thickness of patches.

Table No.3.5

% Elongation of Indomethacin patches of batch F1 to F11

Formulation

Elongation (%)

F1

72.43 ± 4.23

F2

40.46 ± 5.32

F3

46.32 ± 3.96

F4

54.78 ± 4.65

F5

58.93 ± 5.20

F6

61.98 ± 3.85

F7

64.87 ± 6.24

F8

65.87 ±5.32

F9

67.15 ± 4.34

F10

69.19 ± 5.12

F11

71.43 ± 3.24


3.6.3. Folding endurance

Folding-endurance of film were found to be satisfactory between 69.23 ±

7.29 to 120.87± 5.86.This shows that patches would maintain their

integrity and not break easily during handling.

Table No.3.6

Folding endurance of Indomethacin patches of batch F1 to F11

Formulation

Code.

Folding endurance

F1 120.87 ± 5.86

F2

69.23 ± 7.29

F3

85.56 ± 5.35

F4

87.23 ± 4.56

F5

94.53 ± 7.23

F6

105.23 ± 5.63

F7

109.51 ± 5.89

F8

110.21 ± 4.76

F9

114.56 ± 3.66

F10

116.33 ± 4.61

F11

117.45 ± 4.14


3.6.4. Tensile strength

Tensile-strength were found to be in between of 3.93 ± 00.15 to 5.94 ±

00.17 N/mm2as the concentration of hydrophilic polymer HPMC E5 and

hydrophobic polymers Ethyl cellulose increases the tensile strength was

found to be increased.

Table No.3.7

Tensile strength of Indomethacin patches of batch F 1 to F11

Formulation

Code.

Tensile strength

(Kg/mm 2)

F1

3.93 ± 0.15

F2

5.94 ± 0.17

F3

5.08 ± 0.13

F4

4.98 ± 0.19

F5

4.81 ± 0.21

F6

4.34 ± 0.22

F7

4.09 ± 0.16

F8

3.92± 0.19

F9

3.56 ± 0.22

F10

3.32 ± 0.12

F11

3.09 ± 0.17


3.6.5. Flatness

All films shows 100% flatness. Table No.3.8

Flatness of Indomethacin patches of batch F1 to F11

Formulation

Code.

Flatness

F1

100

F2

100

F3

100

F4

100

F5

100

F6

100

F7

100

F8

100

F9

100

F10

100

F11

100


3.6.6. Moisture uptake

The % moistures uptake of Indomethacin patches were between 2.47

to 4.54 % at 75% RH and 3.12 to 5.98% RH at 85% RH. The moisture

uptake increases as concentration of hydrophilic polymer increases

and decreases as concentration of hydrophobic polymer increases.

As the moisture uptake was less, patches were not moisture sensitive

during storage.

Table No.3.9

Moisture uptake of Indomethacin patches of Batch F1 to F11

Formulation 75%RH 85 %RH

F1

4.54 ± 0.19

5.98 ± 0.20

F2

2.47 ± 0.21

3.12 ± 0.31

F3

2.80 ± 0.29

3.47 ± 0.23

F4

3.13 ± 0.24

3.80 ± 0.19

F5

3.59 ± 0.23

4.03 ± 0.25

F6

3.91 ± 0.12

4.20 ± 0.18

F7

4.03 ± 0.17

4.78 ± 0.15

F8

4.15 ± 0.12

4.92 ± 0.30

F9

4.27 ± 0.21

5.13 ± 0.15

F10

4.34 ± 0.24

5.43 ± 0.21

F11

4.51 ± 0.12

5.61 ± 0.25


3.6.7. Percent moisture loss

The % moisture loss of Indomethacin patches were between 2.27 to

4.32 %. The moisture content increases as concentrations of hydro-

philic polymers increases. Also, as moisture-contents was less.

Patches were not moisture sensitive during storage.

Table No.3.10 % moisture loss of Indomethacin patches batch F1 to F11

Formulation

% Moisture content

F1

4.32 ± 0.20

F2

2.27 ± 0.15

F3

2.41 ± 0.09

F4

2.53 ± 0.18

F5

2.87 ± 0.16

F6

3.21 ± 0.18

F7

3.51 ± 0.25

F8 3.67 ± 0.16

F9

3.75 ± 0.24

F10

3.91 ± 0.18

F11

4.18 ± 0.09


3.6.8. Moisture vapour transmittance rate

Moisture vapour transmittance rate increases as the concentration of

hydrophilic polymer increases between the ranges 1.58 to 3.87 %.

Table No.3.11 Moisture vapour transmittance rate of Indomethacin patches

Batch F1 to F11

Formulation

MVTR

F1

3.87± 0.32

F2

1.58 ± 0.21

F3 1.7 ± 0.19

F4

1.98 ± 0.32

F5

2.23 ± .024

F6

2.65 ± 0.26

F7

2.90 ± 0.24

F8

3.03 ± 0.18

F9

3.12 ± 0.26

F10

3.27 ± 0.19

F11

3.49 ± 0.21


3.6.9. Weight variation

The weight variation of Indomethacin patches were in between 473 to 479

mg. This showed uniformity in weight of patches.

Table No.3.12

Weight variation of Indomethacin patches batch F1 t o F11

Formulation

Average

Weight(mg)

F1

475.20 ± 5.20

F2

477.32 ± 4.1

F3 479.13 ± 3.8

F4

478.13 ± 3.2

F5

474.32 ± 4.9

F6

478.43 ± 3.4

F7

474.13 ± 4.13

F8

473.50 ± 3.11

F9

478.32 ± 4.51

F10

475.66 ± 3.48

F11

475.31 ± 4.23


3.6.10. Drug content

The % drug content of Indomethacin in patches were between 97.64 to

100.41 % this shows equal drug content in patches

Table No.3.13

Drug content of Indomethacin patches batch F1 to F1 1

Formulation

% Drug content

F1

98.57 ± 0.34

F2

99.11 ± 0.29

F3 99.24 ± 0.39

F4

98.95 ± 0.24

F5

97.91 ± 0.27

F6

100.41 ± 0.31

F7

97.94 ± 0.38

F8

97.64 ± 0.50

F9

99.45 ± 0.48

F10

99.25 ± 0.38

F11

100.11 ± 0.21


Time in hrs

F1

0

0

1

25.93

2

35.92

3

44.41

4

57.02

5

69.17

6

77.8

7

81.47

8

90.12

9

90.65

10

90.91

11

91.17

12

91.85

24

92.09

Cum

ula

tive

% D

rug

Dif

fus

ion

3.7.1. Invitro drug diffusion study of Indomethacin Transdermal pa tch

Batch F1

Invitro Diffusion study of Batch F1

100

90

80

70

60

50 F1

40

30

20

10

0

0 10 20 30

Time in hrs

Table No.3.14 Batch F1

Figure No.3.10: Invitro Diffusion study of Batch F1

Time in hrs

F2

0

0

1

6.87

2

10.91

3

14.59

4

17.55

5

20.93

6

23.6

7

25.98

8

28.5

9

31.98

10

34.5

11

36.12

12

38.98

24

55.61

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F2


60

50

40

30

F2

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F3

0

0

1

8.02

2

12.31

3

15.36

4

18.68

5

21.41

6

24.51

7

26.91

8

29.5

9

32.4

10

35.4

11

37.98

12

40.42

24

61.91

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F3


70

60

50

40

30 F3

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F4

0

0

1

8.82

2

13.32

3

17.85

4

20.27

5

22.91

6

24.81

7

27.36

8

30.13

9

33.41

10

36.46

11

38.91

12

41.46

24

63.19

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F4


70

60

50

40

F4 30

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F5

0

0

1

9.1

2

14.91

3

19.77

4

22.98

5

23.5

6

25.91

7

28.42

8

32.49

9

35.32

10

37.32

11

40.19

12

43.13

24

65.18

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F5

Invitro Diffusion Study of Batch F5

70

60

50

40

F5 30

20

10

0

0 10 20 30

Time in hrs

Table No.3.18

Batch F5


Time in hrs

F6

0

0

1

9.92

2

15.03

3

19.91

4

22.79

5

24.91

6

27.41

7

29.92

8

33.41

9

36.91

10

38.97

11

42.13

12

44.41

24

67.22

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F6


80

70

60

50

40

F6

30

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F7

0

0

1

10.28

2

15.92

3

19.95

4

22.85

5

25.63

6

28.91

7

31.68

8

35.51

9

38.03

10

41.18

11

43.46

12

45.91

24

69.77

Cum

ula

tive

% D

rug

Dif

fus

ion


Batch F7


80

70

60

50

40

F7

30

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F8

0

0

1

11.43

2

17.67

3

21.45

4

25.87

5

29.54

6

31.59

7

33.98

8

37.41

9

40.32

10

43.89

11

45.79

12

49.11

24

75.28

Cum

ula

tive

% D

rug

diff

usi

on


Batch F8


80

70

60

50

40

F8

30

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F9

0

0

1

16.11

2

21.54

3

27.87

4

33.39

5

41.51

6

48.9

7

56.61

8

63.77

9

71.39

10

77.59

11

79.21

12

80.54

24

81.25

Cum

ula

tive

% D

rug

diff

usi

on


Batch F9


90

80

70

60

50

F9 40

30

20

10

0

0 10 20 30

Time in hrs



Time in hrs

F10

0

0

1

19.17

2

24.57

3

33.87

4

36.49

5

46.32

6

52.81

7

59.65

8

68.21

9

77.59

10

79.91

11

81.43

12

83.83

24

87.81

Cum

ula

tive

%D

rug

dif

fus

ion


Batch F10

Invitro Diffusion study of batch F10

100

90

80

70

60

50

40

30

20

10

0

0 10 20 30

F10

Time in hrs

Table No.3.23

Batch F10


Time in hrs

F11

0

0

1

21.17

2

27.53

3

35.82

4

41.34

5

48.51

6

56.97

7

63.62

8

68.75

9

79.36

10

80.19

11

83.48

12

86.76

24

88.61

Cum

ula

tive

% d

rug

Dif

fusi

on


Batch F11


100

90

80

70

60

50

40

30

20

10

0

0 10 20 30

F11

Time in hrs



3.7.12. Invitro drug diffusion study of Indomethacin Transdermal pa tches

Time in

hrs

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

1

25.93

6.87

8.02

8.82

9.1

9.92

10.28

11.43

16.11

19.17

21.17

2

35.92

10.91

12.31

13.32

14.91

15.03

15.92

17.67

21.54

24.57

27.53

3

44.41

14.59

15.36

17.85

19.77

19.91

19.95

21.45

27.87

33.87

35.82

4

57.02

17.55

18.68

20.27

22.98

22.79

22.85

25.87

33.39

36.49

41.34

5

69.17

20.93

21.41

22.91

23.5

24.91

25.63

29.54

41.51

46.32

48.51

6

77.8

23.6

24.51

24.81

25.91

27.41

28.91

31.59

48.90

52.81

56.97

7

81.47

25.98

26.91

27.36

28.42

29.92

31.68

33.98

56.61

59.65

63.62

8

90.12

28.5

29.5

30.13

32.49

33.41

35.51

37.41

63.77

68.21

68.75

9

90.65

31.98

32.4

33.41

35.32

36.91

38.03

40.32

71.39

77.59

79.36

10

90.91

34.5

35.4

36.46

37.32

38.97

41.18

43.89

77.59

79.91

80.19

11

91.17

36.12

37.98

38.91

40.19

42.13

43.46

45.79

79.21

81.43

83.48

12

91.85

38.98

40.42

41.46

43.13

44.41

45.91

49.11

80.54

83.83

86.76

24

92.09

55.61

61.91

63.19

65.18

67.22

69.77

75.28

81.25

87.81

88.61

Table No.3.25: Invitro drug diffusion study of Indomethacin Transdermal

patches of batches F1 to F11

Cum

ula

tive

% D

rug

Dif

fus

ion

3.7.13. Comparative Invitro drug diffusion study of Transdermal patches

Comparative Diffusion Study of Batches F1 to F11

100

90

80

70

60

50

40

30

20

F1

F2

F3

F4

F5

F6

F7

F8

F9

F10

F11

10

0

0 5 10 15 20 25 30

Time(hrs)

Figure No.3.21: Comparative Invitro drug diffusion study of Transdermal

patches of batch F1 to F11

The Indomethacin matrix type Transdermal Patches shows drug diffusion

through Franz diffusion type of diffusion cell, the relationship can be

established as follow:

F1 > F11 > F10 > F9 > F8 > F7 > F6 > F5 > F4 > F3 > F2

It can be said that increasing concentration of Ethyl cellulose, decreased

cumulative % drug diffusion was found. Hence, by different quantity of

polymers in films, percent diffusion can be different as per our rational.

Drugs polymers attraction can be a main aspect that controls diffusion of

drugs from the patches. From the diffusion studied batches the batch F8

show linear drug diffusion in 24 hours. Therefore batch F8 selected as

optimized batch and further studies for accelerated stability study.

3.8. Stability Studies

Stability-study was performed at temperature 400C and 75% RH for 180

days.

Table No.3.26

Stability studies of Indomethacin Transdermal patch es of batch F8 %

drug content and Tensile strength at 180 days

Time

(days)

% Drug content

Tensile strength

(kg/mm 2)

0

97.64 ± 0.50

3.92± 0.19

60

97.53±0.31

3.87± 0.16

120

97.39±0.21

3.68± 0.12

180

97.09

3.55


3.8.1. Comparative stability studies for drug diffu sion of Indomethacin

Transdermal patches of batch F8

Batch F8 is selected as optimized batch and further studied for stability

Study 400C ± 20C & RH 75 ± 5% for 180 days.

Table No.3.27:

Stability studies for % drug diffusion of Indometha cin Transdermal

patches of batch F8 at 180 days

Time (hr) Cumulative % Drug diffused at 0 days

Cumulative % Drug diffused at 180 thdays

0

0 0

1

11.43 9.89

2

17.67 13.23

3

21.45 17.89

4

25.87 21.89

5

29.54 25.32

6

31.59 28.35

7

33.98 30.23

8

37.41 32.03

9

40.32 37.56

10

43.89 39.13

11

45.79 43.06

12

49.11 45.89

24

75.28 72.96

Cum

ula

tive

% D

rug

di

ffu

siom

3.8.2. Comparative Stability studies for drug Diffu sion of batch F8 40 0C ± 20C & RH 75 ± 5% after 180 days.

Comparative stability studies at 0 days and after 180 days of batch F8

80

70

60

50

0 day 40

180 days

30

20

10

0

0 10 20 30

Time in hrs

Figure No.3.22:

Stability studies for drug Diffusion of batch F8 at 40oC and 75% RH after

180 days

3.9. Conclusion

Finally, we conclude that the formulated transdermal patches of

Indomethacin showed good thickness, drug content uniformity and tensile

strength. The used polymer (Hydroxy propyl methylcellulose E5: Ethyl

cellulose) can be used to develop transdermal patches in 6:4 proportions.

As the concentration of hydrophilic polymer increases the folding endurance

also increases, the increased folding endurance shows the good film

consistency. In moisture uptake study the moisture uptake is going

decreases while the concentrations of ethyl-cellulose were

increases. From drug diffusion study, it is conclude that, when the

concentrations of ethyl cellulose increase the In-vitro drugs diffusion rate

decreases.

chapter3. formulations and invitro evaluation of...

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