This document summarizes research conducted to develop fast-dissolving tablets containing ketorolac and rizatriptan using direct compression method. Four formulations were prepared and evaluated for properties like disintegration time, wetting time, and drug release. Formulation F4, containing mannitol, microcrystalline cellulose, crospovidone and Kyron T-134, showed the fastest disintegration and drug release within minutes. Stability studies of F4 at 25°C/60%RH and 40°C/75%RH for 3 months found no significant change in properties. Overall, the study demonstrated the effectiveness of combining crospovidone and Kyron T-134 as superdisintegrants

1. Effect of Kyron T-134 and Crospovidone as a Fast Disintegrating
Agent on the Formulation Properties of a Fast Dissolving Tablet
Containing Ketorolac and Rizatriptan Using the Direct Compression
Method
By
Rawand Sirwan
Supervised by
Dr. Nozad Rashid
Erbil – Kurdistan
12-January/2023

2. My acceptance Letter from Zanco Journal for Medical Science

3. Outlines
Introduction
Aim and Objective
Methodology
Results & Discussion
Conclusion
References

4. Introduction
Dysphagia, or difficulty in swallowing,
affects roughly 35% of the population as a
whole.
>35%
FDTs
Ketorolac is a morphine-like NSAID used to
relieve migraine headache. It can no
selectively bind and inhibit both COX
enzymes, but predominantly COX-1.
Ketorolac 10 mg
Rizatriptan 5 mg
Rizatriptan is a serotonin receptor agonist. It
works by constricting brain blood vessels,
reducing pain, nausea, and other migraine
symptoms.

5. Introduction
Ketorolac
Rizatriptan
+

6. Introduction
Ketorolac 10 mg
+
Rizatriptan 5 mg
FDTs
Success Combination
No water
intake Migraine attack
First-pass effect Gatstric upset
Dysphagia
(Auratic & Non-auratic)

7. This research aimed to develop fast-dissolving ketorolac and
rizatriptan tablets.
By using the direct compression method, it is the most popular
and simplest approach to manufacturing this innovative dosage
form.
It ensures that a large amount of the drugs dissolve in the mouth
quickly (within minutes, most likely in less than one minute), which
enhances drug bioavailability.
Aim

8. To find out how different types of diluents and super disintegrants affect the
wetting time, water absorption ratio, disintegration, and dissolution time of oral
dissolving tablets of ketorolac and rizatriptan made using the direct compression
technique.
To compare the prepared FDT with the marketed product as a fast-dissolving oral
dosage form in terms of disintegration, as disintegration is considered a critical
characteristic for the fast-dissolvable dosage forms.
To research and test the improved formulation tablets in a variety of conditions.
To increase the rate at which medications are released by shortening the time it
takes for the prepared tablets to disintegrate.
Objectives

9. Material
Ketorolac and Rizatriptan were purchased from
Glentham Life Science, UK.
Crospovidone, Sodium starch glycolate, Strawberry,
Sodium saccharin, Citric acid, Aerosil, and Magnesium
stearate were received as a gift from Awamedica Industry,
Erbil.
The Kyron T-134 was received as a gift from Corel
Pharma Chem, India.

10. Pre-formulation studies:-
FT-IR (Jasco-4600)
Determination of the Melting point of drugs
Determination of λmax (maximum absorbance) of drugs
Determination of calibration curve of drugs
Determination of the Flowability of the powder mixture
Method
1. Bulk and tapped
denisty
2. Angle of Repose
3. Compressability
(carr’s index) &
haunser’s ratio

11. Preparation of FDTs
+
Ketorolac 10 mg Rizatriptan 5 mg
F1
F2
F3
F4
=
=
=
=
Mannitol(57.8) + MCC(20mg) + crospovidone (3 mg)
Mannitol(65.8) + MCC(10mg) + Kyron T-134 (5 mg)
Mannitol(76.8) + sodium starch glycolate (4 mg)
Mannitol(45.8) + MCC(30 mg) + crospovidone (2.5 mg)
Diluents Superdisintegrants
+
(2.5 mg Kyron T-134
+
Other excipients
+
Prepared FDTs (F4)
Direct compression
Flat round punch
6.5 mm
Flavouring agent
(strawberry)
Sodium Saccharin
Citric Acid
Magnesium
stearate
Aerosil

12. Evaluation of FDTs
Visual inspection Friability test Hardness test Thickness & diameter test
Weight variation Disintegration test
Dissolution test
& drug content
Wetting time + Water absorption
ratio

13. Comparability study
V.S.
Prepared FDTs Marketed FDTs
In-vitro disintegration test
Electrolab
Disintegration tester-3
USP
Time Time
900 ml of distilled
water at 37 °C + 0.5
Analysis

14. Stability study
25 °C with 60 ± 5 relative
humidity (RH)
40 °C with 75 ± 5 relative
humidity (RH)
Thickness = 25 micron
Packaging Bottle
Newtronic
stability chambar
(AwaMedica)
Cotton balls

15. Results and Discussion
Ketorolac Rizatriptan
Ket-Riz Comb.
*Changing the organoleptic
features of the formulation
before, during, and after the
direct compression process

16. 5
0.290
10
0.450
15
0.598
20
0.760
25.000
0.910
y = 0.03100x + 0.1366
R² = 0.9998
0.000
0.100
0.200
0.300
0.400
0.500
0.600
0.700
0.800
0.900
1.000
0 5 10 15 20 25 30
ABSORBANCE
Concentration (PPM)
5
0.150
10
0.240
15
0.330
20
0.410
30.000
0.560
y = 0.01780x + 0.0608
R² = 0.9999
0.000
0.100
0.200
0.300
0.400
0.500
0.600
0 5 10 15 20 25 30 35
ABSORBANCE
Comcentration (PPM)
The UV spectrum and calibration curve
of Ketorolac in deionised water
The UV spectrum and calibration curve
of Rizatriptan in deionised water

17. Results and Discussion
Flow
properties
F N Mean ± SD P value
Angle of
Repose Ø
F4 3 24.98 ± 1.45 0.001
Carr’s
index* (%)
F4 3 7.16 ± 0.54 0.004
Haunser’s
ratio*
F4 3 1.08 ± 0.02 0.019
Bulk density
g/ cm-3 F4 3 0.65 ± 0.02 0.001
Tapped
density
g/ cm-3
F4 3 0.71 ± 0.02 0.001
(F4) Powder Mixture Excellent Flowability?
Mannitol DC 400 Crospovidone Kyron T-134

18. Results and Discussion
0
5
10
15
20
25
30
35
40
45
F1 F2 F3 F4
Thickness (mm) Hardness (N)
*
*
0
10
20
30
40
50
60
70
F1 F2 F3 F4
Disintegration (sec) Wetting time (sec) water absorption ratio (%)
P = 0.001
P = 0.751
*
*
*
P = 0.001

19. Results and Discussion
45.6
66.1
88.9
93.3
99.4 99.8 100.7
0
20
40
60
80
100
120
0 2 4 6 8 10 12 14 16
%
Ketorolac
released
Time (min)
84.6
99.7
100.4 100.3 100.1
82
84
86
88
90
92
94
96
98
100
102
0 1 2 3 4 5 6
%
Rizatriptan
released
Time (min)
Percentage release of rizatriptan from FDTs prepared with combining
two different super disintegrants (Kyron T-134 + crospovidone).
Percentage release of ketorolac from FDTs prepared with combining two
different super disintegrants (Kyron T-134 + crospovidone).
D2 min%
D2 min%
T80 %
T80 %

20. Results and Discussion
The percentage of Rizatriptan drug content in FDTs prepared by
combining two different super disintegrants (Kyron T-134 +
crospovidone).
The percentage of ketorolac drug content in FDTs prepared by
combining two different super disintegrants (Kyron T-134 +
crospovidone).
98%
0%
20%
40%
60%
80%
100%
120%
F4
%
of
ketorolac
content
Formulation
93%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
F4
%
of
rizatriptan
content
Formulation

21. Results and Discussion
10 10.27
11.41
5
6
7
8
9
10
11
12
13
14
15
Disintegration
time
(sec)
at time zero at 25C 60 RH at 40C 75 RH
P = 0.349
*
0
20
40
60
80
100
120
2 4 6 8 10 12 15
%
ketorolac
released
at time zero at 25C 60 RH at 40C 75 RH
75
80
85
90
95
100
105
2 4 6 8 10
%
rizatriptan
released
at time zero at 25C 60 RH at 40C 75 RH
% of release for Ketorolac during stability study % of release for Rizatriptan during stability study
Disintegration time of prepared FDTs (F4)

22. Results and Discussion
10
64.8
0
10
20
30
40
50
60
70
Disintegration
time
(sec)
F4 Marketed product FDTs
*
P = 0.001

23. Graphic conclusion
+
Rizatriptan 5 mg
Ketorolac 10 mg
+
Kyron T-134 2.5% Crospovidone 2.5%
Mannitol 45.8 mg MCC 30 mg
+
Could be
Best combination
Best combination
As FDTs
The fastest
disintegration
tendency
Diluents with
additional
disintegration
properties

24. References
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25. Thank You For Your attention!