ijrpb 1(4) 18 page 565-569

ISSN: 2321-5674(Print)

ISSN: 2320 3471(Online) Rajesh et.al. Indian Journal of Research in Pharmacy and Biotechnology

Volume 1(4) July-August 2013 Page 565

FORMULATION OF MOUTH DISSOLVING TABLETS OF NAPROXEN Rajesh Reddy K, Nagamahesh Nandru, Desam Asha Latha, Srinivasa Rao Chekuri

MRR College of Pharmacy, Nandigama, Andhra Pradesh, India

Corresponding author: Email: [email protected]

ABSTRACT

The aim of the present work is to investigate the possibility of preparing mouth dissolving tablet

containing naproxen by direct compression method. Basic goals in the development of mouth dissolving tablet

are to increase patient compliance, ease of administration, safety and appropriate dosing. It has perceived

faster onset of action as the dosage form is disintegrated prior to reaching the stomach and is ideal for acute

diseases like allergies, nausea, and vomiting and particularly applicable to manage breakthrough systems.

Direct compression method was used to compress the tablets as it is the easiest way to manufacture tablets and

less time consuming. Conventional equipment, commonly available excipients and limited number of

processing steps are involved in the direct compression and so manufacturing cost is low. Keeping in view the

advantages of this delivery system, in the present study, attempts were made to formulate mouth dissolving

tablet.

Key words: Naproxen, Mouth dissolving, Disintegration.

INTRODUCTION

Mouth Dissolving Tablet is an innovative tablet

technology where the dosage form containing active

pharmaceutical ingredients disintegrates rapidly, usually

in a matter of seconds, without the need for water,

providing optimal convenience to the patient. Innovators

and inventor companies have given these tablets various

names such as orally disintegrating tablets (ODT),

mouth dissolving (MD), fast melting, fast dissolving or

Orodisperse. The European Pharmacopoeia defines

Orodisperse as a tablet that can be placed in the mouth

where it disperses rapidly before swallowing.

Researchers have formulated ODT for various

categories of drugs, which are used for therapy in which

rapid peak plasma concentration is required to achieve

desired pharmacological response. These include

neuroleptics, cardiovascular agents, analgesics, anti-

allergic and drugs for erectile dysfunction.

MATERIALS AND METHODS

Naproxen was obtained as an gift sample form

Granules India, Hyderabad, Microcrystalline cellulose,

Mannitol, Crosscarmellose sodium, Sodium starch

glycollate, Crosspovidone, Aerosil, Aspartame and

Magnesium stearate was obtained from Kniss

laboratories Pvt limited, Chennai

Pre-formulation studies

Preparation of mixed blend of drug and excipients:

All the Ingredients were passed through mesh 60.

Required quantity of each ingredient was taken for each

specified formulation and all the ingredients were cog

rind in a mortar and pestle. The powder blend was

evaluated for flow properties such as Bulk density,

Tapped density, Compressibility index, Hausner ratio

and angle of repose.

Evaluation of Naproxen Mouth Dissolving Tablets:

The formulated tablets has been evaluated for the

following parameters such as Thickness, Weight

variation test, Hardness test, Friability test, Water

absorption Ratio Content uniformity test, Wetting time,

In-vitro dispersion time and In-vitro dissolution studies

RESULTS AND DISCUSSION

Surface Morphology: Morphological characteristics

such as colour, form, taste etc of naproxen were studied

and the results are tabulated in table. As the API is bitter

in taste, taste masking with sweetener may prove

beneficial for a palatable dosage form.

Physical parameters: The pure drug showed angle of

repose value is 35031

1indicates the good flow properties.

The compressibility index, Hausners ratio values of the

drug are 28.40% and 1.397 indicates that the drug has

poor compressibility properties.

Drug Excipient compatibility studies

Fourier transforms infra-red spectroscopy (FTIR): The FTIR analysis was conducted for the structure

characterization. FTIR spectra of the pure drug, pure

polymers and mixture of both were recorded.

Formulations were taken in a KBr pellet using BOMEN

MB SERIES FTIR instrument. Approximately 5mg of

samples were mixed with 50mg of spectroscopic grade

Kbr; samples were scanned in the IR range from 500 to

3500 cm-1

, with a resolution of 4 cm-1

.

Compatibility Studies: Drug excipient compatibility

study showed no interactions as principle peaks are

retained. Thus all excipients were compatible with drug.

Optimized formula: The dissolution profile of

formulations (F1-F6) indicates a faster release of drug

i.e. 90% or more of the drug released from all

formulations with in 60 min. however the maximum




release of drug (99.4%) was observed in F4.This

formulation also exhibited better performance in the

other evaluation parameters. Hence, formulation (F4) is

selected as optimized formula.

Table 1: Formula for Naproxen Mouth Dissolving Tablets

Ingredients (Mg) F1 F2 F3 F4 F5 F6

Naproxen 150 150 150 150 150 150

Microcrystalline Cellulose 18 10 18 10 18 10

Mannitol 26 14 26 14 26 14

Croscarmellose sodium 40 60 - - - -

Table: 2 Identity Parameters of API

Test Specifications Results

Description:

Colour

Odour

Form

Taste

white

None

Crystalline

Bitter

Complies

Solubility Soluble in ethanol and methanol Complies

Identification:

IR-Spectrum

IR-Spectrum of the test sample should match

with the IR-Spectrum of the working standard.

Complies

Assay 99% w/w 99.0% to 101.0% w/w

All the Identity parameters of the API are found to be within the limits

Table: 3 Physical parameters of API in Pre-

formulation studies

Table: 4 Ftir Spectrum of the Naproxen

parameters Result

Tapped density 0.728 gm/ml

Bulk density 0.521 gm/ml

Compressibility Index 28.40 %

Hausner Ratio 1.397

Angle of repose 35031

1

Type of Vibrations Range

C=O 1788

C-H 3192

C-C 1631

C-O 1028

Table No: 5 Pre-compression properties of the naproxen mouth dissolving tablets.

Formulation Bulk density

(g/ml)

Tapped density

(g/ml)

Hausners Ratio Carrs index

Angle of repose

(0o)

F1 0.530.005 0.620.02 1.160.02 13.651.06 31'

F2 0.520.01 0.610.014 1.180.03 14.271.06 30.

F3 0.5260.005 0.610.014 1.160.01 14.780.18 279'

F4 0.520 0.60 1.150 14.580 32.05'

F5 0.5260.01 0.6050.01 1.1630.02 12.510.02 29.82'

F6 0.5260.005 0.630.08 1.1630.005 14.890 27.21'

The data are expressed as meanS.D. (n=3)

Table: 6 Post compression properties of the naproxen mouth dissolving tablets.

Formulation Weight

variation (mg)

Thickness

(mm)

Hardness

(kg/cm2)

Friability

(%)

Disintegration

Time (sec)

F1 Passes 3.740.02 3.630.15 0.50 28 0.54

F2 Passes 3.760.02 3.80.1 0.450.12 26 0.02

F3 Passes 3.260.02 4.030.05 0.410.22 25 0.14

F4 Passes 3.140.02 3.330.11 0.220.08 26 0.25

F5 Passes 3.210.03 3.80.1 0.80.08 27 0.14

F6 Passes 3.66 0.05 4.030.15 0.620.16 24 0.01





Table: 7 Post compression properties of the naproxen mouth dissolving tablets

Formulation Water absorption

Ratio

Content

uniformity

Wetting time

(sec)

In-vitro dispersion

time(Sec)

F1 78.92 0.14 98.19 0.51 50.663.05 114.664.16

F2 72.35 0.41 98.42 1.01 43.333.05 93.34.16

F3 69.32 0.58 97.77 1.26 262 74.34.04

F4 75.63 0.47 99.82 0.33 182 551.0

F5 74.21 0.25 99.740.44 72.663.05 93.62.51

F6 74.23 0.14 98.500.55 67.333.05 842


Table: 8 Cumulative Percentage drug Release of F1 F6in pH 6.8 Phosphate Buffer

Time

(min)

Cumulative Percentage Of Drug Release in pH 6.8 Phosphate Buffer

F1 F2 F3 F4 F5 F6

10 42.8 56.6 68.6 78.6 68.4 76.8

20 70.6 64.8 74.8 79.8 74.8 83.6

30 78.4 80.6 86.4 84.8 76.6 91.8

40 84.6 84.8 90.6 91.4 88.4 95.8

50 88.8 92.8 94.8 97.8 89.6 97.4

60 92.6 94.7 96 99.4 96.6 98.7

Table: 9. Optimized formulas of Naproxen Mouth dissolving tablet

Ingredients Quantity (mg)

Naproxen 150

Microcrystalline cellulose 10

Mannitol 14

Crospovidine 60

Aerosil 2

Aspartame 10

Magnesium stearate 4

Total 250

Fig 1: FTIR of naproxen

Fig 2: FTIR of naproxen with croscarmellose

sodium




Fig 3: Ftir Of Naproxen With Crospovidone Fig 4: FTIR of naproxen with sodium starch

glycolate

Fig 5: Formulated mouth dissolution for naproxen mouth dissolving tablets

15 Sec 30Sec

45 Sec 55 Sec

Fig 6: Disintegration time at the end of Various time interval

Fig :7 In-vitro drug release of mouth dissolving tablets of Naproxen (F1-F6)




CONCLUSION

The demand for orally disintegrating tablets

has enormously increased during the last decade,

particularly for geriatric and pediatric patients who feel

difficulty in swallowing conventional tablets and

capsules. Fast dissolving or fast disintegrating dosage

form is advantageous for such patients. Fast dissolvable

or fast disintegrating dosage forms are meant to

disintegrate immediately upon contact with the saliva

leading to faster release of drug in the oral cavity. By

administrating the fast disintegrating dosage forms,

absorption of the drugs occurs through buccal mucosa

and it may reduce the first pass metabolism leading to

better efficacy of the drug. In my present work an

attempt was made to develop mouth dissolving tablets of

naproxen by direct compression method and by using

cross povidone, cross carmellose sodium and sodium

starch glycolate as superdisintegrants. In the

preformulation studies it has been proved that there is no

interaction between the drug and the excipients. The

blends of varying super disintegrants were formulated

into 6 formulations ranging from F1 to F6, and the blends

were evaluated for the pre and post comparison

parameters and In vitro drug release is also studied. All

the pre compression parameters angle of repose, Cars

index, Hausners ratio, tapped and bulk density and is within the limits. The results shown that the

formulations containing the Cross povidone have the

good flow properties and the good compactability when

compared with the other formulations. The post

compression parameters include the Weight variation,

Hardness, friability, Thickness, wetting time, In vitro

disintegration and In vitro dispersion time and the water

absorption ratio. The results shown maximum for the

formulation (F4) that containing the cross povidone as

superdisintegrant. The In vitro drug release of

formulation F4 had shown that maximum drug release

99.4 0.54 when compared with the other formulations.

So F4 was choosen as the best formulation which

contains crosspovidone as a super disintegrant. The

naproxen 250 mg mouth dissolving tablet was prepared

by using the finalized formula and optimized

manufacturing process showed good results in

formulation of stable tablet dosage form.

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ijrpb 1(4) 18 page 565-569