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Presented by:
D.Sumanth
14031S0405
CONTENTS:
AIM & OBJECTIVE OF WORK
INTRODUCTION
LITERATURE REVIEW
DRUG PROFILE
PROGRESS OF WORK
VALIDATION
SUMMARY
REFERENCE
guidelines.
2.INTRODUCTION:
DISSOLUTION:
DESCRIPTION
DOSAGE FORM
TYPE 1
Basket apparatus
IR,DR,ER
TYPE 2
Paddle apparatus
IR,DR,ER
TYPE 3
Reciprocating cylinder
IR,ER
TYPE 4
ER , Poorly soluble
TYPE 5
TRANSDERMAL
TYPE 6
Rotating cylinder
TRANSDERMAL
TYPE 7
Reciprocating holder
ER
DESIGN:
Cell types:
Tablets 12 mm
Tablets 22.6 mm
Powders / Granules
Suppositories /
Soft gelatincapsules
Implants
3.LITERATURE REVIEW:
Literature review was done seeing for an method on
estimation of triamcinolone acetonide in injectable
suspensions
Pharmacopoeias like USP , B.P, I.P, E.P
Scholarly articles from pubmed , science direct
Internet
4.DRUG PROFILE:
Triamcinolone acetonide:
Molecular weight:434.49
g/mol
Molecular formula:C24H31FO6
Chemical structure
Chemical name: 9 -fluoro-11 ,21dihydroxy16 ,17 -isopropylidenedioxy-l,4pregnadiene-3,20-dione.
TECHNICAL INFORMATION:
Appearance
:Crystalline
Physical State
:Solid
Solubility
:Insoluble in water
Melting point
:292-294C
Mechanism of action:
Triamcinolone acetonide binds to specific cytosolic
glucocorticoid receptors and subsequently interacts with
glucocorticoid receptor response element on DNA and alters gene
expression. This results in an induction of the synthesis of certain
anti-inflammatory proteins while inhibiting the synthesis of
certain inflammatory mediators. Consequently, an overall
reduction in chronic inflammation and autoimmune reactions are
accomplished.
5.PROGRESS OF WORK:
Instruments and material used:
Dissolution tester :CE7 smart, Make : Sotax
HPLC systems
:Agilent with VWD/DAD Model:1200series
Water
Filters
sample
suspension
Dissolution parameters
Media
:sodium dodecyl sulphate solution
Temperature
:370.5C
Flow rate
:4,8,16 ml per minute
Flow type
:laminar or turblent flow
Filters
:glass fiber and glass wool filters
Sample volume :20ml
Factors influencing drug release in dissolution apparatus
Media
Flow rate
Trial-1
Media
Flow rate
Trial-2
Media
Flow rate
Media
:0.50% sodium dodecyl sulphate
Temperature
:370.5C
Apparatus
:USP type IV open loop Offline
Type of cell
:22.6mm
Glass beads loading :13g
Type of filter
:glass micro fiber GF/C (whatmann)
Flow rate
:8 ml/minute
Sample volume :20ml
Time points
:5,10,15,20,30,40,50,60,70,80,90&120
minutes
PREPARATION OF SOLUTIONS:
Preparation of dissolution media:
Weigh and transfer 5.0g of sodium dodecyl sulphate into 1000ml of
water
Diluent preparation:
Water and Acetonitrile are mixed in ratio of 35:65% v/v
Standard stock preparation:
Trial-1
Column
: ODS 2504.6mm,5m
Mobile phase
:30:70(Acetonitrile : Water)
Flow rate
:1.0ml/min
Injection volume
:10l
Wavelength
:254nm
Column temperature:30C
Runtime
:20min
Trial-2
Column
:Zorbax Eclipse C181504.6mm,5m
Mobile phase
:30:20:50(ACN : methanol : water)
Flow rate
:1.2ml/min
Injection volume :10l
Wavelength
:254nm
Column temperature:30C
Runtime
:20min
Trial-3
Column
:Inertsil ODS 3V 1504.6mm,5m
Mobile phase
: 50:50 (ACN : water)
Flow rate
:1ml/min
Injection volume :10l
Wavelength
:254nm
Column temperature:30C
Runtime
:5 min
Optimised method:
Column
:Inertsil ODS 3V 1504.6mm,5m
Mobile phase
:60:40(ACN : water)
Flow rate
:1ml/min
Injection volume :10l
Wavelength
:254nm
Column temperature:30C
Runtime
:5min
6. Validation:
To perform Validation studies for the developed method and
the Validation parameters include:
Specificity
Linearity
Accuracy
Precision
LOD
LOQ
Robustness
System suitability
A. Specificity:
I. Blank interference:
Dissolution medium is used as blank sample solution and it should
not show any peak in the chromatogram.
II. Placebo interference:
Preparation of placebo:0.2 g of Polysorbate 80 was weighed and
transferred into 500ml volumetric flask and sonicated for 30min to
form clear solution and to it 7.5 g of Carboxymethyl cellulose, 1 g
of sodium chloride and 1 ml of benzyl alcohol was added and
sonicated to form clear solution.
Blank and Placebo samples are injected and analysed.
Chromatogram of Blank
Chromatogram of Placebo
Observation: No interference of Blank or Placebo is observed
B. Linearity:
Preparation of stock solution: Weighed and transferred 55.625 mg of
Triamcinolone Acetonide in to 50ml volumetric flask added 30ml of
diluent sonicate for 5min to dissolve and make up to the mark with diluent.
Dilutions are made from stock solution to get required ppm and made the
volume with dissolution media.
Dilution
ppm Obtained
Area Obtained
1 ml in 250 ml
4.45
65229
1 ml in 100 ml
11.12
156878
2 ml in 100 ml
22.24
314849
3 ml in 100 ml
33.36
462506
4 ml in 100 ml
44.48
625447
5 ml in 100 ml
55.60
753576
6 ml in 100 ml
66.72
911033
800000
600000
Response 400000
area
200000
0
0
10
20
30
40
50
60
70
Concentration in g/ml
80
C. Accuracy
A series of sample solutions were prepared in triplicate by
spiking the Triamcinolone Acetonide with placebo in the range
of 10% to 150% and injected into HPLC system and analyzed.
Amount
added(mg/ml)
Amount
recovered(mg/ml)
% Recovery
0.0045
0.00445
98.9
0.0045
0.00453
100.7
3.
0.0045
0.00458
101.8
1.
0.0453
0.0444
98.0
0.0453
0.0458
101.1
3.
0.0453
0.0448
98.9
1.
0.0542
0.0555
102.4
0.0542
0.0543
100.2
0.0542
0.0541
99.8
S. No.
% Spike
level
1.
2.
2.
2.
3.
10%
100%
120%
Mean
%recovery
%RSD
100.4
1.5
99.3
100.8
1.6
1.4
D. Precision
S. No
% Sipe Level
Amount added
(mg/ml)
0.0453
0.0453
3
100
4
5
6
0.0453
0.0453
0.0453
0.0453
Amount
Recovered(mg/ml)
0.0445
0.0458
0.0452
0.0449
0.0448
0.045
% Recovery
Mean %Recovery
%RSD
98.23399558
0.974
98.23399558
101.1037528
99.77924945
99.11699779
98.89624724
99.33774834
E. Limit of Detection
A series of solution were prepared and injected till the Signal to
Noise ratio is greater than 3.
F. Limit of Quantification
Solutions approximately 3.3 times the concentration of LOD was
prepared and injected to observe Signal to Noise ratio of 10
G. Robustness
Change in flow rate:
System suitability
parameters
As such
Results
+Flow
-Flow
(1.0
mL/min)
(1.2
mL/min)
(0.8
mL/min)
Acceptan
ce
criteria
0.09
0.17
0.14
NMT 2.0
5035
4113
5440
NLT 2000
Tailing factor
1.1
1.1
1.1
NMT 2.0
Change in temperature
Results
System suitability
parameters
As such
(25C)
-Column oven
temperature
(20C)
+Column
oven
temperature
Accepta
nce
criteria
(30C)
0.09
0.15
0.44
NMT
2.0
Theoretical plates
5035
4766
4776
NLT
2000
Tailing factor
1.1
1.1
1.1
NMT
2.0
H. System suitability
100% solution was prepared and injected as six replicates
System suitability parameters
Results
Acceptance criteria
0.26
NMT 2.0
Theoretical plates
6123
NLT 2000
Tailing factor
1.24
NMT 2.0
Summary
Parameters
Triamcinolone Acetonide
4.5-66.72 ppm
Optimized wavelength
254 nm
Retention time
2.76
0.999
Correlation coefficient(r2)
y = 13563x+8679
Precision (% RSD)
3.5
Percentage Recovery
99.3
0.18
0.56
7.REFERENCE
Pharmacopoeias USP , B.P , I.P
http://www.slideshare.net/shettyuc/dissolution-33496242/1
http://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_g
etallData.cfm
http://en.chembase.cn/molecule-165706.html
www.dissolutiontech
.com/DTresour/201111Articles/DT200505_A05.pd
www.dissolutiontech
.com/DTresour/201111Articles/DT201111_A06.pd
www.dissolutiontech
.com/DTresour/201111Articles/DT201111_A02.pd
https://www.researchgate.net/publication/237445416
www.usp.org/sites/default/files/usp_pdf/EN/gc_1092.pdf
https://hmc.usp.org/sites/default/files/documents/HMC/GCs
-Pdfs/c
1225.pdf
www.us.edu.pl/uniwersytet/jednostki/wydzialy/chemia/acta
/ac18/.../11_AC18.pdf
www.chromacademy.com
Thank you