WELCOMETO

KAMLA NEHRU INSTITUTE OF MANAGEMENT AND

TECHNOLOGYSULTANPUR, U.P.

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Project PresentationOn

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

ANTIBACTERIAL ACTIVITY

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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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

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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.

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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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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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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(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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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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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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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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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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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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RESULT ANALYSIS

PREFORMULATION

1- Organoleptic Properties

2- Standard Calibration Curve of Norfloxacin

Colour Yellowish White

Odour Odourless

Taste bitter

1 2 3 4 5 60

0.2

0.4

0.6

0.8

1

1.2

absorbanceLinear (absorbance)

Concentration

Absorbance

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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.

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Flow Properties

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

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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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% 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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DRUG RELEASE KINETIC OF FORMULATION

1 2 3 4 5 60

10

20

30

40

50

60

70

80

90

100

F1

F2

F3

F4

F5

F6

Time in Minutes

% Drug Release

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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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Rate of zone of inhibition of S. aureus and E. coli by disk diffusion method.

F1 F2 F3 F4 F5 F60

2

4

6

8

10

12

14

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Zone of inhibition of S. aureus and E. coli

S. aureusE. coli

Formulations

Zone of Inhibition (In mm)

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

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MINIMUM INHIBITORY CONCENTRATION

• Method-Broth Dilution Method• Media – Muller Hinton Broth• Species- A) Gram Positive- Staphylococcus aureus

B) Gram Negative- E. coli• Solvent- DMSO

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Minimum inhibitory concentration for s.aureus and E.coli

Minimum inhibitory concentration for staphylococcus aureus.

Minimum inhibitory concentration for E.coli.

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

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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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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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