FORMULATION AND CHARACTERISATION OF ORAL DISPERSIBLE TABLET OF APREPITANT

GUIDED BY:Dr. ZANKHNA SETHASSISTANT PROFESSOR and HEAD OF DEPARTMENTS.K.C.O.P

PRESENTED BY:BHAKTI. M. SHAHM.PHARM SEM IV(PHARMACEUTICS)ENROLLMENT NO. 132460808013S.K.C.O.P

Department of PharmaceuticsSat Kaival College of Pharmacy

1

2

LITERATURE REVIEW

CONTENT

2

1. AIM OF WORK &OBJECTIVE

3.RATIONAL

4. REVEIW OF LITERATURE

5. DRUG PROFILE

2. INTRODUCTION

6. PRE-FPRMUATION STUDY

7. MATERIAL & METHODOLOGY

8.RESULT

9. SUMMARY &CONCLUSION

10.COMPLANCE REPORT

11. REFRENCES

3

AIM & OBJECTIVE OF WORK To formulation and characterization of oral dispersible

tablets of an anti-emetic drug by direct compression. The oral route of drug administration is more common

and convenient where tablets and capsules emerged as popular dosage form but many patients have dysphasia or difficulty in swallowing which is currently affecting 35% general population.

Difficulty in swallowing (Dysphasia) is a common problem of all age groups, especially the elderly and pediatrics because of physiological changes associated with these groups.

4

RATIONALE

Aprepitant is an antiemetic drug which induced nausea and vomiting during the treatment of chemotherapy.

Aprepitant is neurokinin 1 receptor antagonist . Neurokinin 1 receptor available in brain in high concentration on

vomiting center and reflex of its create vomiting. In aprepitant injectable approach are available ,but this approach are

very costly , time consuming, pain full and dose not use for pediatric and geriatric patient.

Oral dispersible method are very easy to prepare ,patient compliance and economic method.

so, compare to injectable method this approach are reliable Hence, the present work is aimed at the formulation and evaluation

of aprepitant oral dispersible tablet

5

What are ODT?Solid dosage form

Rapiddisintegrationon the tongue

A stable, oral dosage formwith the dosing ease of a liquid.

Fast DissolveDosage Form

Oral route ofadministration

6

INTRODUCTION

Oral Dispersible tablet are solid single unit dosage forms that are placed in mouth , allowed to disperse or dissolve in saliva without need of water for frequently release of drug for quick onset of action.

Oral Dispersible tablet disappears rapidly before swallowing.

Disintegrates in 15 sec to 1 min. Also called as fast dissolving tablet, orodispersible tablet,

melt in mouth tablet, repimelts tablet, porous tablet.

[1,2;3}

7

Aprepitant may also be useful in the treatment of cyclic vomiting syndrome & late-stage chemotherapy induced vomiting.

Aprepitant use as a antiemetic, anxiolytic and anti depressant

8

LITERATURE SURVEY

9

LITURATURE REVIEW Sr. no.

Researcher Drug Superdisntegr

antDosage form Journal

1

Deshmukh, A. K. Seth. Tejas K Ghelani, Sharad Kumar,

Hemangi Patel, Sachin Chauhan[1]

Famotidine

Crospovidone,Croscarmelose

sodiumOro dispersible tablet

Indo American Journal Of

Pharmaceutical Research

2Leela Manasa K,

Ramana G and Digpati Roy [2]

Alfuzosin Hydrochloride

Crospovidone,Croscarmelose

sodiumOro dispersible tablet

Journal of Applied

Pharmaceutical Science

3

Milind P Wagh*, Chetan P Yewale, Santosh U Zate, Paresh I Kothawade, Ganesh H Mahale[3]

AceclofenacCrospovidone,Croscarmelose

sodiumOro dispersible tablet

International Journal of

Pharmacy and Pharmaceutical

Sciences

4

*Devendra Revanand Rane, Hemant Narhar Gulve, Vikas Vasant

Patil, Vinod Madhaorao Thakare, Vijay

Raghunath Patil [4]

AlbendazoleCrospovidone,Croscarmelose

sodiumOro dispersible tablet

International Current

Pharmaceutical Journal

10

Researcher Drug Polymers Dosage form Journal

5

B Chandrasekhara Rao, S Vidyadhara ,

RLC Sasidhar and YA Chowdary[14]

Aprepitant

Polyethylene glycol- 4000 Polyethylene glycol- 8000

Solid dispersion

Research Journal of

Pharmaceutical, Biological and

Chemical Sciences

6

P. Durga Bhavani, S. Venkata Ramana Reddy, Laxmidhar

Sahoo, K. Harinadha Baba[15]

AprepitantCarboxy methyl cellulose sodium

Nano suspension

International Journal of Advanced

Pharmaceutics

11

DRUG PROFILE

Structure of Etodolac

Systematic (IUPAC) Name:5-([(2R,3S)-2-((R)-1-[3,5-

bis(trifluoromethyl)phenyl]ethoxy)-3-(4-fluorophenyl)morpholino]methyl)-1H-1,2,4-triazol-

3(2H)-one

Molecular formula C23H21F7N4O3

Molecular weight 534.4gm/mol

Color and appearance Off white crystalline powder

Category Anti –emetic , Neurikinin receptor bloker

BCS class Class –II

Log P 5.22

pka Acidic(9.65)Basic(3.51)

[15]

12

Solubility Insoluble water

Sparingly soluble EthanolSlightly soluble in acetonitrile

Melting point

244-246 °C

Indication Mainly use for the treatment ofAnti emetic

Half life 9 -13 hours

Bioavailability(%) 60 – 65 %

Excretion Urine(5%) and feaces (86%)

Metabolism stomach

UV Absorption 210 nm

13

Mechanism of action Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis.

Side effect abdominalpain,changedsenseoftaste,constipation,diarrhea,Dizziness,dry mouth, fatigue,flushing, headache, heartburn, loss of appetite, muscle cramps, upset stomach, vomiting, weakness

14

Mechanism of Aprepitant

15

15

SUMMARY OF PSAR

Sr no.

PSAR Title name

1 US2013/0317016A1 APREPITANT INJECTABLE FORMULATION

2 US8497303B2 METHOD TO ENHANCE AQUEOSUES SOLUBILITY OF POORLY SOLUBLE ACTIVES

3 US 2010/0092564A1 COMPOSITION OF METHOD FOR PREPARING ORALLY DISINTEGRATING TABLTS

4 US 739050B1 ONDASETRON ODT

5 US 2001/0014532A2 COMPRESSED TABLETS FORMULATION

PSAR SUMMARY

16

Looikng of above patent. the patent is available in injectable approach on Aprepiatnt drug. the patent are available other dosage form and field of chemistry. that mean s no patent are available related to my dissertation topic aprepitant are indicated for the nausea and vomiting . there are severable formulation are available of aprepitant like injectable. dosage form oral dosage method are easy to prepare , patent compliance, and economic method . there is no available about oro dispersible tablet of Aprepiatnt that’s why i am selecting this topic

17

Preformulation Study

Formulation of dispersible tablet

Optimization Study

Stability Studies

EXPERIMENTAL WORK

18

Pre-formulation study

Observed value

Standard value(17)

245˚C 244-246˚C

Melting point

19

SR NO. SOLVENT SOLUBILITY

1 Water Insoluble

2 Ethanol Sparingly

3 Aceto nitrile Slightly

4 Di- methyl formide(DMF) Soluble

Solubility of Aprepitant

20

IR spectrogram of Etodolac

Interpretation of FT-IR Spectra

3. FTIR

21Data for Calibration Curve

Calibration Curve of Aprepitant data

Concentration(μg/ml) Abs(nm)±SD

5 0.071±0.016

10 0.194±.0017

15 0.321±0.018

20 0.473±0.018

25 0.614±0.017

30 0.728±0.014

35 0.907±0017

4.Calibration curve

22

0 5 10 15 20 25 30 35 400.000

0.200

0.400

0.600

0.800

1.000

f(x) = 0.026752380952381 x − 0.0427142857142825R² = 0.999542949161075

Aprepitant at 210nm

Ab

so

rba

nc

e

Concentration(μg/ml)

Calibration Curve of Aprepitant

23

Materials &Method

Materials uses

Aprepitant Drug carrier

Polyplasdone XL 10 superdisintegrant

Polyplasodone XL superdintegrant

Polyplasdone INF10 superdisintegratint

Crosscarmelose sod ium superdisintegratint

SSG superdisintegratint

Spray dried lactose filler

Mannitol diluent

Sodium stearyl fumarate lubricant

Straw berry flavour Flavour

Aspatartame Swetner

24

SR NO. EQUIPMENT COMPANIES NAME

1 Electronic weighing balance Metter Toledo PG403-S,Denver Instrument

2 Melting point appratus VMP-1(VEEGO)

3 Hot air oven Hicon,ELE InsrumentPvt.ltd

4 Disintegration appratus Krishna engineering

5 Tablet compression machine Hicon Insrument

6 Dissolution Appratus VDA-6D USPStd.(VEEGO)

7 U.V.Visible Spectrometer

UV-1700(Shimadzu Inc. Japan)

8 Hardness tester Hicon 9 Roche friability Electro Lab

10 Digital bulk density Mitutoyo

11 Vernier calipers Electro lab bulk density tester USP,ETD-1020

25

S1 Aprepitant : SSG ( 1:1)

S2 Aprepitant : SSG (1:3)

S3 Aprepitant : SSG (1:5)

S4 Aprepitant : CROSPOVIDONE (1:1)

S5 Aprepitant : CROSPOVIDONE (1:3)

S6 Aprepitant : CROSPOVIDONE (1:5)

P1 Aprepitant : SSG (1:5)

P2 Aprepitant : CROSPOVIDONE (1:5)

D Pure Drug

Solid dispersion (kneading method)

26

Time (min) Cumulative Drug Release

S1 S2 S3 P1 D5 91.81±1.01 98.04±0.11 87.82±0.13 34.59±0.93 0

10 102.01±0.13 98.04±0.58 91.25±0.95 41.25±0.48 10.57±0.77

20 101.67±0.56 101.0±0.91 95.02±0.78 42.99±0.19 19.78±0.37

30 98.79±0.49 100.32±1.01 94.26±0.79 52.79±0.63 30.11±0.93

45 98.63±0.69 100.32±0.35 95.77±1.17 63.35±0.17 45.59±0.18

60 99.29±1.12 100.32±0.51 91.25±0.95 76.18±0.49 52.68±0.83

IN VITRO DISSOLUTION STUDY OF SOLID DOSAGE FORM

Solid dispersion by kneading method in 6.8 buffer pH solution.

27

Time (min) Cumulative % Drug Release

S4 S5 S6 P2 D

5 97.28±0.27 94.26±0.61 99.55±0.19 24.39±0.79 0

10 101.43±0.89

103.55±1.16

97.34±0.87 39.89±0.19 10.57±0.77

20 99.55±0.61 101.85±1.07

98.85±0.29 41.25±0.48 19.78±0.37

30 98.79±0.94 100.98±0.58

97.33±0.64 49.02±0.87 30.11±0.93

45 97.74±1.06 100.98±0.48

92.62±0.35 55.81±0.58 45.59±0.18

60 98.5±0.73 99.56±0.83 94.12±1.03 64.11±0.49 52.68±0.83

28

0 10 20 30 40 50 60 700

20

40

60

80

100

120

S1S2S3P1D

TIME(min)

%C

DR

Figure no: dissolution profile of solid dispersion S1,S2,S3 in comparision with pure drug and physical mixture(P2) in 6.8 buffer pH.

29

0 10 20 30 40 50 60 700

20

40

60

80

100

120

S4S5S6P2D

Dissolution Profile of solid dispersion

%C

DR

Figure no: dissolution profile of solid dispersion S4,S5,S6 in comparison with pure drug and physical mixture(P2) in 6.8 buffer pH.

30

TRIAL BATCHES

31

INGREDIENTS(mg) A1 A2 A3 A4 A5 A6 A7 A8 A9 A10

Aprepitant 80 80 80 80 80 80 80 80 80 80

Mannitol 68 62 68 62 68 62 68 62 68 62

Spray.dried lactose 44 40 44 40 44 40 44 40 44 40

Polyplasdone XL 20 30 - - - - - - - -

Polyplasdone XL 10 - - 20 30 - - - - - -

Polyplasdone INF 10 - - - - 20 30 - - - -

Cross carmeloss

sodium

- - - - - - 20 30 - -

Sodium starch

glycolate

- - - - - - - - 20 30

Arosil 200 5 5 5 5 5 5 5 5 5 5

Mg.Stearate. 2 2 2 2 2 2 2 2 2 2

Powder Flavoure

(strawberry)

1 1 1 1 1 1 1 1 1 1

Total 220 220 220 220 220 220 220 220 220 220

32

FACTORIAL BATCHES

33

LEVAL

FACT OR

-1 0 +1

POLYPLASDONE

XL10

26mg 30mg 34mg

MANNITOL 50mg 56mg 62mg

32 FACTORIAL DESIGN Independent variables:

Polyplasdone XL10 Mannitol

Dependent variables: Disintegration time(sec) Wetting time(sec)

34

BATCH NO. X1 X2F1 -1 -1

F2 -1 0

F3 -1 +1

F4 0 -1

F5 0 0

F6 0 +1

F7 +1 -1

F8 +1 0

F9 +1 +1

35

INGREDIENT(mg)

F1 F2 F3 F4 F5 F6 F7 F8 F9

Aprepitant 80 80 80 80 80 80 80 80 80

Mannitol 50 56 62 20 56 62 50 56 62

Spray dried lactose

44 40 44 40 44 40 44 40 44

PolyplasdoneXL 10

26 26 26 30 30 30 34 34 34

Aerosil200 5 5 5 5 5 5 5 5 5

Mg.Stearate 2 2 2 2 2 2 2 2 2

Powder flavour (straw berry)

1 1 1 1 1 1 1 1 1

Factorial Design Batches

36

RESULTS AND CONCLUSION

37

Evaluation Parameter for Tablet

Pre-compression parameters

Bulk density

Tapped Density

Carr’s Index

Hausner’s ratio

Angle of repose

Post-compression parameters

Tablet Thickness

Tablet Hardness

Weight variability

Friability

Drug content uniformity

In-Vitro Drug Release Study

38

Post formulation study

Batches Avg. Wt(mg) ±SD

Hardness(kp) ±SD

Thickness(mm ) ±SD

Friability(%w/w)

Drug content%±SD

A1 220.12±0.01 4.91±0.77 3.91±0.05 0.64 98.19±0.01

A2 219.85±.001 4.88±0.79 3.87±0.05 0.69 97.23±0.01

A3 219.82±0.04 4.18±0.96 3.89±0.06 0.79 97.76±0.01

A4 220.05±0.01 4.67±1.08 3.92±0.06 0.94 97.89±0.04

A5 219.78±0.02 4.62±2.97 3.91±0.04 0.89 97.26±0.03

A6A7

219.83±0.01219.95±0.01

4.09±1.104.52±0.85

3.90±0.04 0.97 97.48±0.02

3.63±0.03 0.75 98.02±0.01

A8 220.10±0.01 4.65±0.72 3.85±0.04 0.93 97.65±0.02

A9 219.87±0.02 4.95±0.81 3.73±0.05 0.72 98.15±0.01

A10 219.98±0.01 4.23±0.73 3.78±0.04 0.86

97.59±0.03

##±SD=n=20 ###±SD=n=10

39

Batches Bulk density(gm/cm3)

±SD

Tapped density

(gm/cm3)

±SD

Hausner's ratio

%±SD

Carr’s Index(%)

±SD

Angle of repose

(Ɵ) ±SD

A1 0.51±0.01 0.60±0.01 1.31±0.01 23.71±0.01 23.29±0.01

A2 0.45±0.01 0.52±0.01 1.15±0.01 14.41±0.01 22.47±0.02

A3 0.45±0.03 0.54±0.04 1.18±0.01 15.6±0.02 20.18±0.01

A4 0.49±0.01 0.55±0.01 1.13±0.02 11.76±0.02 21.8±0.03

A5 0.43±0.02 0.51±0.03 1.19±0.01 16.38±0.01 23.89±0.01

A6 0.41±0.01 0.49±0.01 1.18±0.02 15.83±0.01 23.8±0.02

A7 0.42±0.02 0.53±0.01 1.17±0.01 17.23±0.02 22.57±0.02

A8 0.47±0.01 0.57±0.02 1.16±0.02 13.52±0.01 20.42±0.01

A9 0.44±0.01 0.56±0.01 1.21±0.01 18.21±0.01 24.2±0.01

A10 0.46±0.02 0.59±0.03 1.23±0.01 12.29±0.02 21.56±0.03

Preliminary screening batches pre-formulation study

##±SD=n=3

40

Disintegration time(sec) Wetting time(sec)

A1 48.±2 52.±3

A2 43.±1 50±2

A3 37.±3 41±1

A4 36.±4 38±2

A5 38.±5 43±1

A6 40.±2 44±3

A7 61.±3 64±2

A8 63.±1 66±3

A9 56.±2 59±1

A10 58.±1 61±2

41

Bulk densitygm/cm3±SD

Tapped density(gm/cm3) ±SD

Hauser ratio ±SD

Carr's index%±SD

Angle of repose (Ɵ) ±SD

F1 0.20±0.01 0.30±0.01 1.15±0.06 20.7±0.012 26±0.03

F2 0.17±0.01 0.31±0.01 1.19±0.01 22.6±0.016 21±0.01

F3 0.21±0.02 0.35±0.02 1.18±0.03 23±0.020 24.2±0.01

F4 0.19±0.01 0.29±0.01 1.17±0.04 20±0.019 22.3±0.02

F5 0.16±0.02 0.26±0.01 1.15±0.01 18.2±0.016 24.5±0.01

F6 0.22±0.01 0.32±0.02 1.19±0.03 21.5±0.023 23.6±0.01

F7 0.18±0.01 0.34±0.01 1.16±0.02 19.6±0.013 25.1±0.01

F8 0.17±0.02 0.28±0.01 1.17±0.01 20.5±0.015 22±0.01

F9 0.24±0.01 0.33±0.01 1.18±0.01 21±0.014 23±0.02

PRECOMPRESION PARAMETER OF FACTORIAL BATCHES

42

Avg. Wt(mg)±SD

Hardness (kp) ±SD

Thickness(mm) ±SD

Friability(%w/w)

±SD

Drug content

±SDF1 220.20±2.30 4.45±0.71 3.89±0.03 0.398 98.07±0.12

F2 219.80±2.10 4.04±0.79 3.91±0.05 0.430 99.01±0.57

F3 220.50±2.64 3.99±0.84 3.91±0.04 0.532 98.00±0.98

F4 220.40±1.90 3.90±0.75 3.87±0.03 0.521 97.90±0.7

F5 219.80±1.62 4.78±0.21 3.93±0.02 0.562 99.1±.0.22

F6 220.1±1.20 4.33±0.82 3.93±0.03 0.432 99.45±0.14

F7 218.90±1.85 3.52±0.45 3.90±0.02 0.356 99.56±0.28

F8 220.90±1.73 4.30±0.80 3.91±0.01 0.486 98.14±0.91

F9 221.10±1.85 4.31±0.70 3.93±0.02 0.512 99.21±0.45

POST COMPRESION PARAMETER OF FACTORIAL BATCHES

43

Factorial batches Disintegration time(sec)

Wetting time(sec)

F1 35.±2. 36±1

F2 28.±1 30.±1

F3 31.±1. 32±4

F4 34.±2 35±2

F5 27.±1 28.±2

F6 29.±1. 31.±1

F7 32.±2 33.±2.

F8 23.±2. 23±3.

F9 24.±1. 25.±1

44

R square 0.9903

Adjusted R square 0.9741

SOURCE

COEFFICIENT P – value

β0 +27.55 0.0032

β1 -2.40 0.0032

β2 -2.93 0.0018

β12 -1.59 0.0453

β22 +4.69 0.0023

STATITICAL ANALYSIS The response (Y) is measured for each trial. Y = B0 + B1X1 + B2X2 + B12X1X2 + B1

1X12 + B2

2X22

REGRESION OF Y1(DISINTEGRTION TIME)

45

Design-Expert® SoftwareFactor Coding: ActualR1 DT (sec.)

Design points above predicted valueDesign points below predicted value35

23.02

X1 = A: A conc of polyplasdone XL 10X2 = B: B conc. of mannitol

-1

-0.5

0

0.5

1

-1

-0.5

0

0.5

1

22

24

26

28

30

32

34

36

R1

DT

(s

ec

.)

A: A conc of polyplasdone XL 10 (mg)

B: B conc. of mannitol (mg)

Full model equation

Y1= 27.55-2.40X1-2.93X2-1.5X12 +4.69x22

 

46

R square 0.9743

Adjusted R square 0.9316

SOURCE

Coefficient P value

β0 +28.26000 0.0136

β1 -2.77000 0.0086

β2 -2.52333 0.0112

β12 -0.81000 0.2374

β12 -1.36000 0.1789

β22 +4.87000 0.0082

REGRESION OF Y2 (WETTINGTIME)

47

Design-Expert® SoftwareFactor Coding: ActualR2 WT (sec.)

Design points above predicted valueDesign points below predicted value36.23

23.39

X1 = A: A conc of polyplasdone XL 10X2 = B: B conc. of mannitol

-1

-0.5

0

0.5

1

-1

-0.5

0

0.5

1

22

24

26

28

30

32

34

36

38

R2

WT

(s

ec

.)

A: A conc of polyplasdone XL 10 (mg)

B: B conc. of mannitol (mg)

Full model equationY2= +28.26 -2.77X1-2.93X2 – 0.81X1X2-1.36X1

2+4.87X22

 Reduced model equation on the basis of P value Y2= 28.26-2.77X 1-2.52X2 + 4.87X2

2

48

TIME(min) F1 F2 F3 F4 F5 F6 F7 F8 F9

0 0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

0.000± 0.0

5 46.51± 0.65

52.16± 0.25

52.69± 0.65

45.34± 0.41

54.18± 0.99

54.42± 0.56

48.38± 0.75

55.67± 0.55

56.13±0.89

10 60.49± 0.83

62.45± 0.91

63.99± 0.29

65.12± 0.47

65.44± 0.59

65.86± 0.53

66.87± 0.63

67.23±0.45

69.85± 0.31

1574.43± 0.43

74.97± 0.87

76.56± 0.95

77.86± 0.91

78.15± 0.74

79.12± 0.65

79.16± 0.61

80.49± 0.54

82.53±0.78

2082.67± 0.52

83.69± 0.32

85.20± 0.86

85.25± 0.82

86.45± 0.38

86.72± 0.25

86.86± 0.28

89.2 ±

0.55

90.23± 0.67

2589.49± 0.67

91.52± 0.85

93.64± 0.45

94.61± 0.49

95.79± 0.86

96.27± 0.65

97.20± 0.12

98.42±0.64

99.25± 0.3

3090.52 ±

0.8993.21±

0.4296.56±

0.7897.40±

0.2597.98±

0.0298.34±

0.8599.51±

0.4299.99±

0.2599.78±

0.48

In Vitro Drug Release study of Dispersible tablet (F1-F9)In 6.8 buffer pH solution

±SD=n=6

49

0 5 10 15 20 25 30 350

20

40

60

80

100

120

F1F2F3F4F5F6F7F8F9

time(min)

%C

DR

In vitro drug release profile

50

TIME(min) INITIAL AFTER 30 DAYS0 0 05 55.67 55.45

10 67.23 66.7815 80.49 79.86

20 89.2 88.74

25 98.42 98.15

30 99.83 99.76

STABILITY STUDY

0 5 10 15 20 25 30 350

20

40

60

80

100

120

INITIALAFTER 30 DAYS

Time (min)

%C

DR

51

Stability at 40ºc /75%RH

Batch no F8 optimsed Initial After 30 days

Avg.wt 220.0.2 219.98

Hardness 4.30 4.19

Thickness 3.91 3.89

Friaility 0.484 0.462

Disingration time (sec) 20.83(1.23) 21.45(1.86)

Wetting time(sec) 21.56(1.47) 20.63(0.75)

52

SUMMARY AND CONCLUSION

53

Aprepitant is an anti emetic drug which is in used in nausea and vomiting in chemotherapy.

It is a BCS class-II drug so, increases solubility solid dispersion was carried out using kneading method. In 6.8 buffer pH in vitro dissolution was carried out .

For trial batchesA1-A10 were taken respectively. using different superdisintegrant in which after evaluation It was concluded that A4 was optimsed and polyplasdone XL10 is used as superdisintegrant.

For the optimisation of tablet factorial design 32 was carried out. In which independent variable are polyplasdone XL10 and Mannitol . And dependent variable were time and wetting time were carried out. And design was applied.

53

Summary

54

the dissolution was carried out for to increases solubility of aprepitant in 6.8 buffer

pH . Stability study was carried out .F8 was optimisable batch stablisable on

evaluation of it.

55

CONCLUSION The method of preparation of Oral dispersible tablet of Aprepitant

presented in this research work is simple. All formulation showed good physicochemical properties like % Drug release, hardness, thickness, disintegrating time etc.

The in-vitro release data showed that drug release from the

tablet formulation have been affected by types of superdisintegrant and other exepients

These studies indicated that as the concentration of superdisintegrant increased the tablet was decreased disintegration time and increase wetting time.

It was concluded that batch F8 was found to be excellent among all evaluation parameter..

56

57

COMPLAINCE REPORT

SR. NO COMMENT

FULL FILLMENT OF

COMMENT

YES/NO

1

1.Taste masking ----

2.Stability study Yes

3.Experimental design Yes

4.Through research on polyplasdone Yes

5. Statically analysis Yes

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REFERENCES

59

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3. Milind P Wagh,“Formulation And Evaluation of Fast Dispersible Tablets of Aceclofenac Using   Different Superdisintegrant.” I.J.P.phrma,sci. 2010,vol 2.

4. Devendra Revanand Rane, “Formulation and evaluation of fast dissolving tablet of albendazole ”, I.C.P.G , 2012, 1(10), 311-316

5. Sudheshnababu Sukhavasi., “Formulation and evaluation of fast dissolving tablets of amlodipine besylate by using Fenugreek seed mucilage and Ocimum basilicum gum Fundamentals and Applications”, I.C.P.F 2012, 1(9), 243-249

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7. Shailendra Kumar Singh, “Fast Disintegrating Combination Tablets of Omeprazole and Dmperidone” , A.J.pharm.res, Vol.2 2009.

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9. Jayadev Patil , “Formulation, Design And Evaluation of Orally Disintegrating Tablets Of Loratadine Using Direct Compression Process ”, int.j.phar.bio.sci 2011.

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11. Shailesh Sharma, “Formulation of Fast-Dissolving Tablets of Promethazine Theoclate ”, T.j.pharma.res., 2010, 9 (5), 489-497 .

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 15. P. Durga Bhavani, “Formulation And Evaluation of Nanosuspension of Aprepitant By Wet Milling Technique” , Int .J.Adv.Pharm, 2013 ,20-29.16.Apripitant associated no. (APRD00100)13thJUN. 2005.www.drugbank.ca/drugs/DB0067317. .Tushar.Hingori. APRIPITANT injectable formulation.USPTO patent US2013/03177016,2013

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