FORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLET OF NORFLOXACIN WITH PIPERINE AND THEIR ANTIBACTERIAL ACTIVITY

1. SULTANPUR, U.P.

2. Project Presentation
On
FORMULATION AND EVALUATION OF MOUTH DISSOLVING
TABLET OF NORFLOXACIN WITH PIPERINE AND THEIR
ANTIBACTERIALACTIVITY
Presented by
Jayant Kumar Maurya
Roll No.- 1118656503
Under the Supervision of
Mr. Vijay Kumar Singh Prof. (Dr.) G. Mariyappan
Associate Professor, Director, K.N.I.M.T,
Dept. of Pharmaceutics, Sultanpur, (U.P.)
K.N.I.M.T Sultanpur, U.P.)
GAUTAM BUDDH TECHNICAL UNIVERSITY, LUCKNOW, INDIA
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3. CONTENT
Chapter-1
* Introduction
* Drug Profile
* Aim and plan of work
Chapter-2
* Material
* Method of preparation
Chapter-3
* Result and analysis
*Conclusion
*Future prospects
3

4. ABSTRACT
• Drug delivery through oral route is widely accepted through all over
world. Mouth dissolving tablet is most suitable tablet than
conventional tablet. The main characteristics which is in the favors
of mouth dissolving tablet is that there is no need of water to take it.
Due to this it become more suitable dosage form for pediatric and
geriatric patients. Since bioavailability of mouth dissolving tablet is
high than conventional tablet, and mixing of piperine with it make
them much more advance dosage form. Due to the addition of
piperine in the drug, the dose size is reduced, and enhanced the
onset of action. Addition of piperine with norfloxacin also increases
the antibacterial activity and make them more effective.
• Keywords: Mouth dissolving tablet, superdisintigrant, norfloxacin,
piperine, E.coli.
4

5. INTRODUCTION
• The central of drug evaluation and research (CDER), US FDA
defined oral disintegrating tablet (ODT)as, “ A solid dosage
form containing medicinal substance which disintegrate
rapidly, usually within a matter of seconds, when placed upon
the tongue.
• Mouth dissolving tablets (MDT) are single unit dosage form
that dissolve or disintegrate quickly in mouth with the help of
saliva and without the need of water. As these drugs are
quickly dissolve or disintegrate hence it readily available for
absorption improving its bioavailability and onset of action.
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6. ADVANTAGE OF MDT
• No need of water to swallow the tablet.
• Can be easily administered to pediatric, geriatric and mentally disabled patients.
• Dissolution ad absorption of drug is fast, offering rapid onset of action.
• Bioavailability of drug is increased as some drugs are absorbed from mouth,
pharynx, and oesophagus through saliva passing down into stomach.
• First pass metabolism is reduced, thus offering improved bioavailability and thus
reduced dose size and side effect.
• Good mouth feel property of MDT helps to change the perception of medication.
• The risk of chocking or suffocation during oral administration of conventional
formulation due to physical obstruction is avoided, thus providing improved safety.
• Good chemical stability as compared to conventional solid dosage form.
• Provide advantage of liquid medication in the form of solid dosage form.
• Accurate dosing as compared to liquid dosage form.
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7. DRUG PROFILE
• Name : Norfloxacin
• Category : Antibacterial
• Chemical structure :
• Molecular formula : C16H18FN3O3
• Molecular weight : 319.33
• Bioavailability : 35-45%
• Hail-life : 3-5 hours
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8.  (B) Name: Piperine
• Category: alkaloid
• Chemical structure:
• Molecular formula: C17H19O3N
• Melting point: 1290C
• Solubility:
• It is soluble in -petroleum, chloroform, ethanol, methanol and
slightly insoluble In water.
 Physical charaterstics:
• Colour: yellowish white crystalline
• Odour: aromatic
• Taste: aromatic and pungent
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9. PROBLEMS AND ISSUES
• The main problem to therapeutic effectiveness of Norfloxacin
is its, short biological half-life, poor bioavailability and low
therapeutic index.
• The biological half-life of norfloxacin is 3 hours, thus
frequent administration of drug required (3 to 4 times a day) to
maintain constant therapeutic drug levels. This results poor
patient compliance.
• Thus by making making mouth dissolving formulation
piperine the problem may short out which includes
minimization of drug related side effects, maintain the drug
plasma level, improved patient compliance and enhance
bioavailability, reduction of the total dose of drug
administration.
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10. AIM AND OBJECTIVES
Aim-
The aim of the present study is “Formulation and evaluation of mouth dissolving
tablet of norfloxacin with piperine and their antibacterial activity”.
Objective-
• Formulation of fast dissolving tablets of Norfloxacin by direct compression method.
• Rapid onset of action and may offer an improved bioavailability because piperine provides
selective inhibitors of various cytochrome P450 enzymes. Inhibition of these enzymes by
piperine results in enhance bioavailability of drugs Norfloxacin. Thus piperine is absorption
enhancer and a potent inhibitor of drug metabolism.
• Since bioavailability is increased so it’s dosing is reduced.
• Dispersible tablet are perfect fit for pediatric and geriatric patient & those having difficulty in
swallowing.
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11. PLAN OF WORK
• Pre-formulation
studies:
• U.V. Characterizations
• I.R. Characterizations
• Melting point
• Angle of repose.
• Bulk density
• Tapped density
• Compressibility index
• Hausner’s ratio
• Post-compression
studies:
• Hardness
• Thickness
• Weight variation
• Friability
• Wetting time
• Drug content
• Disintegration time
• Dissolution time
• Stability study
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12. DESIGN OF TABLET FORMULATION
Formulation
codes
F1 F2 F3 F4 F5 F6
Norfloxacin 200 200 200 200 200 200
Piperine 15 20 15 20 -- --
SSG 12 15 -- -- 12 --
Crospovidone -- -- 12 15 -- 12
Sod. Saccharine 10 10 10 10 10 10
Lactose 45 45 45 45 45 45
talc 6 6 6 6 6 6
MCC 107 99 107 99 122 122
TOTAL 400 400 400 400 400 400
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13. PREPRATION OF NORFLOXACIN MOUTH
DISSOLVING TABLET
• All the active and inactive ingredients were weighed
accurately.
• Norfloxacin and polymers SSG, Crospovidone and Lactose,
MCC were passed through sieve no. 40# and mixed together in
a polybag.
• Then talc and magnesium sterate pass separately through sieve
no. 40# and added with the above blend.
• Blend was mixed 15 minutes in the polybag.
• Now the prepared blend was directly compressed by a single
station tablet punching machine.
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14. RESULT ANALYSIS
PREFORMULATION
1- Organoleptic Properties
2- Standard Calibration Curve of Norfloxacin
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Colour Yellowish White
Odour Odourless
Taste bitter
0
0.2
0.4
0.6
0.8
1
1.2
1 2 3 4 5 6
Absorbance
Concentration
absorbance
Linear (absorbance)

15. 3- Determination of Melting Point- Melting point of the drug was
determined by capillary method and found 123 0C.
4- Solubility- It has better solubility in water, methanol, ethanol and slight
soluble in isopropyl alcohol and chloroform.
15

16. Flow Properties
16
Formulation
codes
Angle of
repose
(Ө)
Bulk
density
(gm/ml)
Tapped
density
(gm/ml)
Carrs’s
index
Hausner’s
ratio
F1 28.50 + 0.458 0.4160+0.011 0.4628+0.011 12.7 +1.78 1.1011+0.283
F2 23.56 + 0.139 0.4089+0.012 0.4990+0.016 16.21 +1.82 1.2078+0.023
F3 26.38 + 0.015 0.4301+0.013 0.4853+0.113 12.44 +1.81 1.1553+0.029
F4 25.48 + 0.283 0.4122+0.007 0.4751+0.014 13.19 +1.72 1.1422+0.024
F5 27.67 + 0.54 0.4210+0.10 0.4911+0.12 13.54 +1.89 0.1467+0.002
F6 28.78 + 0.223 0.4209+0.009 0.5040+0.014 14.65 + 1.95 1.1671+0.021

17. EVALUATION OF PREPARED TABLET
Formulation
codes
Weight
variation
(%)
Hardness
(kg/cm2)
Friability
(%)
Wetting
time
(sec.)
Disintigration
(sec.)
Drug
content
(%)
F1 400.1 3.4 0.4995 67 78 97.81
F2 398.1 3.3 0.4911 58 70 97.77
F3 399.5 3.6 0.6019 25 37 97.85
F4 402 .3 3.5 0.3991 13 22 98.51
F5 401.5 3.1 0.4026 54 76 97.83
F6 399.2 3.7 0.3995 56 71 97.34
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18. % CDR AND REGRESSION COEFFICIENTS OF
RELEASE KINETIC MODELS
Time in
minutes
F1 F2 F3 F4 F5 F6
1 23.71 29.82 38.85 42.32 24.05 28.43
2 41.43 42.47 56.58 54.62 53.42 48.48
3 56.84 58.28 70.41 73.82 61.29 63.85
4 68.55 70.93 87.91 94.99 70.11 71.23
5 76.30 79.12 93.13 95.61 74.28 77.32
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19. DRUG RELEASE KINETIC OF FORMULATION
19
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6
% Drug Release
Time in Minutes
F1
F2
F3
F4
F5
F6

20. ANTIBACTERIAL ACTIVITY
ZONE OF INHIBITION
• Method-Disc Diffusion Method
• Media – Muller Hinton Agar
• Species-A) Gram (+)ve: S. Aureus
B) Gram (-)ve: E. coli
• Solvent- DMSO
• Concentration – 100 µg/mL
MINIMUM INHIBITION
CONCENTRATION
• Method-Broth Dilution Method
• Media – Muller Hinton Agar
• Species-A) Gram (+)ve: S. Aureus
B) Gram (-)ve E. coli
• Solvent- DMSO
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21. Rate of zone of inhibition of S. aureus and E. coli by disk
diffusion method.
21
0
2
4
6
8
10
12
14
16
F1 F2 F3 F4 F5 F6
Zone of
Inhibition
(In mm)
Formulations
Zone of inhibition of S. aureus and E. coli
S. aureus
E. coli
Rate of zone of inhibition of S. aureus and E. coli by disk
diffusion method.
Sr
.
N
o.
Formul
ation
S. aureus E. coli
ZONE OF INHIBITION (In mm)
1 F1 03 14
2 F2 04 16
3 F3 03 15
4 F4 04 16
5 F5 01 10
6 F6 01 11
Std Vancomycine Amikacine
08 20

22. MINIMUM INHIBITORY CONCENTRATION
• Method-Broth Dilution Method
• Media – Muller Hinton Broth
• Species- A) Gram Positive- Staphylococcus aureus
B) Gram Negative- E. coli
• Solvent- DMSO
22

23. Minimum inhibitory concentration for s.aureus and
E.coli
Minimum inhibitory concentration
for staphylococcus aureus.
Minimum inhibitory concentration for
E.coli.
23
Sr.
No.
Formul
ation
Staphylococcus aureus
25
µg/mL
50
µg/mL
100
µg/mL
200
µg/mL
MIC
µg/Ml
1 F1 Turbid Turbid Turbid Clear 200
2 F2 Turbid Turbid Clear Clear 100
3 F3 Turbid Turbid Clear Clear 100
4 F4 Turbid Turbid Clear Clear 100
5 F5 Turbid Turbid Turbid Turbid >200
6 F6 Turbid Turbid Turbid Turbid >200
Sr.
No.
Formul
ation
E. coli
25
µg/mL
50
µg/mL
100
µg/mL
200
µg/mL
MIC
µg/mL
1 F1 Turbid Clear Clear Clear 50
2 F2 Turbid Clear Clear Clear 50
3 F3 Turbid Clear Clear Clear 50
4 F4 Turbid Clear Clear Clear 50
5 F5 Turbid Turbid Clear Clear 100
6 F6 Turbid Turbid Clear Clear 100

24. CONCLUSION
• The present work efforts have been made to prepare mouth dissolving tablet of
norfloxacin with piperine by direct compression method.
• Release profile of F4 having crospovidone was found to have maximum release 95.61%
at the end of 5 minutes.
• The antibacterial activity showing best result in F2 & F4 for zone of inhibition against S.
aureus & E. coli and F1 to F4 for minimum inhibitory concentration against E. coli.
• Drug content percentage was found maximum in the formulation F4.
• Stability studies were conducted for optimized formulation (F4), the tablet were
analyzed for the hardness, uniformity of drug content and in vitro disintegration time at
the interval of 10 days till a period of 90 days.
• The stability of batches showed no significant variation in all the parameters and was
stable for a period of 90 days. Stability study shows that the % drug release of the drug
decreases with the passes of time.
• Since formulation F4 have the best disintegrating and dissolution time and also have
high drug content as well as high antibacterial activity, hence formulation F4 fulfills the
objective of the present study.
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25. FUTURE PROSPECTIVES
There are some proposed future works which could perform on
the basis of obtained results such as :
• Bioequivalence studies with marketed formulations.
• Stability studies as per ICH guidelines.
• Scale up formulation of optimized batch.
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26. THANK YOU
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