NJEGA ERICK KITHINJIBPHARM UoN U53691452013 SUPERVISORS Shital Shah Maru PhD Tirop Lucy Jemutai PhD OUTLINE Introduction and problem statement Objectives Method Results ID: 693606
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AN EXPERIMENTAL STUDY ON THE BINDER EFFECT OF POVIDONE ON THE MECHANICAL PROPERTIES OF PARACETAMOL CONTAINING TABLETS
NJEGA ERICK KITHINJI(BPHARM
UoN
)
U53/69145/2013Slide2
SUPERVISORS
Shital
Shah
Maru
PhD
Tirop
Lucy
Jemutai
PhDSlide3
OUTLINE
Introduction and problem statement
Objectives
Method
Results
Discussion
Conclusion
Recommendations
Acknowledgments
ReferencesSlide4
1.0 INTRODUCTION AND PROBLEM STATEMENT
Elastic deformation is a reversible process hindering tablet formulation.
Plastic deformation and brittle fracture of particles are irreversible and promote tablet formation. Slide5
1.0 INTRODUCTION AND PROBLEM STATEMENT
Ref:
Aulton’s
pharmaceutics
Figure 1-illustration of particle deformation during compressionSlide6
1.0 INTRODUCTION AND PROBLEM STATEMENT
Paracetamol
mainly exhibits fragmentation and high elastic deformation leading to tablet capping.
Choice of binder is a critical process in
paracetamol
tablet formulationSlide7
2.0 OBJECTIVES
2.1 GENERAL OBJECTIVE
To study the effect of varying povidone binder ratios on the mechanical properties of
paracetamol
containing tabletsSlide8
2.0 OBJECTIVES
2.2 SPECIFIC OBJECTIVES
Formulate and assess the flow properties of
paracetamol
containing granules at different binder ratios of povidone K90 and povidone K30.
To compress the lubricated granules
To study the mechanical properties of the compressed tabletsSlide9
3.0 METHOD
NAME
SOURCE
USE
Paracetamol
BP
Changushu
haugang
, China
Active pharmaceutical
ingredient
Povidone
K30
BP
BASF, Germany
Binder
Povidone K90 BPBASF, GermanyBinderPotassium sorbate BPLab and alliedpreservativeMagnesium stearate BPSigma Aldrich, USALubricant
TABLE 1: TABLE OF MATERIALSSlide10
3.0 METHOD
NAME
SOURCE
USE
Friabilator
Erweka
, Germany
Friability test
Disintegration machine
Erweka
, Germany
Disintergration
test
Hardness
test machine
Schleuniger
, Switzerland
Hardness test
Electronic digital caliperWezu, BelgiumTablet thickness measurementTABLE 2: TABLE OF EQUIPMENTSlide11
3.0 METHOD
3.1 PREPARATION OF DRY TABLETING MIXTURE
A 300g batch formulation of
paracetamol
(85%w/w), corn starch(13%w/w) and potassium
sorbate
(1%w/w) was dry mixed and split into five batches.
3.2 PREPARATION OF GRANULES
A 5%w/w binder concentration made of binary mixtures of povidone K90 and povidone K30 in the ratios of 1:0, 3:1, 1:1, 1:3 and 0:1 was added and mixed in the dry form to the five batches.
Slide12
3.0 METHOD
3.2 PREPARATION OF GRANULES
The dry mixture was massed with the appropriate amount of distilled water for 5 minutes. The wet mass was forced through a 710µm sieve and dried in a hot air oven at 50
0
C for 70 minutes.
The dried granules were passed through a series of sieves; 710µm, 355µm and 180µm.
20% of fines were re-introduced into the sieved granules.Slide13
3.0 METHOD
3.2 PREPARATION OF GRANULES
The sieved granules were lubricated with 1% magnesium stearate and stored in airtight plastic containers for evaluation of flow properties.
Slide14
3.0 METHOD
3.3 EVALUATION OF FLOW PROPERTIES
The parameters measured were
Compressibility index
Hausner’s
ratio
Angle of repose
Flow rateSlide15
3.0 METHOD
TABLE 3: SCALE OF ANGLE OF REPOSE( BP 2012)
Flow property
Angle of repose (degrees)
Excellent
25 – 30
Good
31 – 35
Fair
36 – 40
Passable
41 – 45
Poor
46 – 55
Very poor
56 – 65
Very, very poor
> 66
TABLE 4: SCALE OF COMPRESSIBILITY INDEX AND HAUSNER RATIO (BP 2012)
Compressibility Index
( per cent)
Flow character
Hausner
ratio
1 – 10
Excellent
1.00 – 1.11
11 – 15
Good
1.12 – 1.18
16 – 20
Fair
1.19 – 1.25
21 – 25
Passable
1.26 – 1.34
26 – 31
Poor
1.35 – 1.45
32 – 37
Very poor
1.46 – 1.59
> 38
Very, very poor
> 1.60Slide16
3.0 METHOD
No.
Material
B1
B2
B3
B4
B5
1
Paracetamol
80.00
(300mg)
80.00
(300mg)
80.00
(300mg)
80.00
(300mg)
80.00
(300mg)
2
Corn starch
(
disintegrant
)
13.00
(48.75mg)
13.00
(48.75mg)
13.00
(48.75mg)
13.00
(48.75mg)
13.00
(48.75mg)
3Potassium Sorbate(preservative)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)4PVP K-30(binder)0.00(0.00mg)1.25(4.69mg)2.50(9.37mg) 3.75(14.06mg)5.00(18.75mg)5PVP K-90(binder)5.00(18.75mg)3.75(14.06mg)2.50(9.37mg) 1.25(4.69mg)0.00(0.00mg)6Magnesium stearate(lubricant)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)1.00(3.75mg)7 Total100(375mg)100(375mg)100(375mg)100(375mg)100(375mg)
TABLE 5: TABLET FORMULASlide17
3.0 METHOD
3.4 POST COMPRESSION TESTS
Post compression tests
perfomed
were
Uniformity of weight
Disintegration test
Crushing strength test
Friability testSlide18
3.0 METHOD
3.5 EXPOSURE/EXPLANATORY VARIABLES
varying binder ratios of povidone K90: Povidone K30
1:0, 3:1, 1:1. 1:3, 0:1
3.6 RESPONSE/OUTCOME VARIABLES
Crushing strength friability ratio (CFR)
Crushing strength friability ratio Disintegration time (CSFR:DT)
Slide19
4.0 RESULTS
Figure 2: Batch 1, Batch 2, Batch 3, Batch 4 and Batch 5 GranulesSlide20
4.0 RESULTS
PARAMETER
BATCH 1
BATCH 2
BATCH 3
BATCH 4
BATCH 5
5%w/w binder ratio
K90:K30
1:0
3:1
1:1
1:3
0:1
Bulk Density
(g/ml)
0.50
0.48
0.48
0.48
0.48
Tapped Density(g/ml)
0.59
0.56
0.59
0.59
0.63
Compressibility
Index(%) mean±SD n=3
14.77±0.84
13.77±0.90
19.10±0.79
19.55±0.79
23.93±0.23
Hausner’s Ratio
mean±SD n=3
1.17±0.01
1.16±0.01
1.24±0.011.24±0.011.31±0.01Angle of Repose(˚) mean±SD n=323.77±0.9228.77±0.5823.47±0.9227.93±0.1124.13±0.23Flow rate (g/s) mean±SDn=32.46±0.072.59±0.082.08±0.092.38±0.111.97±0.05Table 6: Table of granule densities and flow propertiesSlide21
4.0 RESULTS
Figure 4: Batch 1, Batch 2, Batch 3, Batch 4 and Batch 5 tabletsSlide22
4.0 RESULTS
PARAMETER
BATCH
1
BATCH
2
BATCH
3
BATCH
4
BATCH
5
5% Binder ratio
K30: K90
0:100
25:75
50:50
75:25
100:0
Tablet thickness(mm)
4.00
4.00
4.00
4.00
4.00
Tablet diameter(mm)
10.00
10.00
10.00
10.00
10.00
Uniformity of weight(mg)
390±0.01
380±0.01
380±0.01
370±0.01
380±0.01
Crushing strength (kgf)
9.08±0.819.12±1.2712.88±0.9411.36±0.8213.00±0.14Tensile strength(N/m2) ×1044.364.396.425.766.40Friability(%)0.34±0.140.88±0.080.69±0.080.91±0.081.05±0.14Crushing strength/Friabilityratio26.7110.3618.6712.4812.38DisintegrationTime(min)99.55±16.5630.74±18.2014.97±5.812.51±0.774.10±1.22Crushing strength friability ratio: Disintegration time0.260.331.244.973.01TABLE 7: TABLE ON POST COMPRESSION TEST ON TABLETS Slide23
5.0 DISCUSSION
TABLE 8: CSFR VALUES FOR THE FIVE BATCHESSlide24
5.0 DISCUSSION
Table 9: CSFR/DT VALUES FOR FIVE BATCHESSlide25
5.0 DISCUSSION
FORMULATION/MODELS
Coefficients
Standard error
t value
Pr
(>|t|)
BATCH 1
26.7059
0.6456
41.366
P<0.0005
BATCH 2
-16.3422
0.9130
-17.899
P<0.0005
BATCH 3
-8.0392
0.9130
-8.805
P<0.0005
BATCH 4
-14.2224
0.9130
-15.577
P<0.0005
BATCH 5
-14.3249
0.9130
-15.690
P<0.0005
R
2
=0.955 Adjusted R
2
=0.9466,
F=107.3,95% confidence
P<0.005TABLE 10: TABLE OF MODELLING FOR CRUSHING STRENGTH FRIABILITY RATIO (CSFR)Slide26
5.0 DISCUSSION
FORMULATION/MODELS
Coefficients
Standard error
t value
Pr
(>|t|)
BATCH 1
0.2505
0.4059
0.617
P=0.5442
BATCH 2
0.2518
0.5741
0.439
P=0.6657
BATCH 3
1.3138
0.5741
2.289
P=0.0331
BATCH 4
5.5200
0.5741
9.615
P<0.0005
BATCH 5
3.2505
0.5741
5.662
P<0.0005
R
2
=0.8669 Adjusted R
2
=0.8402, F=32.56,
95%,P<0.0005
TABLE 11: TABLE OF MODELLING FOR CRUSHING STRENGTH FRIABILITY RATIO DISINTEGRATION TIME (CSFR/DT)Slide27
6.0 CONCLUSION
Batch 1 tablets (povidone K90:poidone K30 of 1:0) have the highest mechanical strength (p<0.005)
Batch 2 tablets (povidone K90:povidone K30 of 3:1) have the lowest mechanical strength (p<0.005
)
Batch 4 tablets (povidone K90:povidoneK30 of 1:3) have the best quality (p<0.0005)Slide28
7.0 RECOMMENDATIONS
Further studies
on
the
effect of povidone on
the compressibility profile of paracetamol
containing
tablets.Slide29
8.0 ACKNOWLEDGMENT
Im
greatly thankful to my supervisors
Shital
Maru
PhD and Lucy
Tirop
PhD for their guidanceI salute all the technologists at the
the pharmaceutics Laboratory university of Nairobi for their support and encouragement.I thank lab and allied Ltd. For gifting me with potassium sorbate BPSlide30
9.0 REFERENCES
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, G.,
Adeagbo
, A.A., 2009.
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properties of a
paracetamol
tablet formulation lubricated with
coprocessed lubricants. Farmacia 57, 500–510.Aulton M.E, (Ed.), 2013. Aulton’s pharmaceutics The design and manufacture of medicines, Fourth Edition. ed.
Churchil
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, M.,
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9.0 REFERENCES
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