INTERNATIONAL JOURNAL OF PHARMACEUTICAL ... 1124.pdfform of the chewable tablet using useful and...

Research Article CODEN: IJPRNK ISSN: 2277-8713 Verma Ritesh, IJPRBS, 2015; Volume 4(5): 1-25 IJPRBS

Available Online at www.ijprbs.com 1

FORMULATION DEVELOPMENT AND EVALATION OF CEPHALOSPORIN CHEWABLE TABLET

VERMA RITESH1, MUKHOPADHYAY SAYANTAN2, CHAUDHARI RAMESH2, SINGH SHARANBIR2,

PROF(DR). KOTHIYAL PREETI2

1 Dept. of Pharmaceutical Science, SGRRITS, Dehradun (U.K), India. 2 Shri Guru Ram Rai Institute of Technology and Science Patel Nager Dehradun 248001.

Accepted Date: 09/08/2015; Published Date: 27/10/2015

Abstract: Aim of this research work was to develop chewable tablet formulation of cephalosporins class with good release for the administration of Drug .To develop a stable form of the chewable tablet using useful and cheap technique. The research investigated in the present study is an attempt towards developing a formulation of Anti-Bacterial drug, which has in-vitro dissolution profile similar or nearby to that of RLD (Reference Listed Drug) formulation but of low cost.

Keywords: Chewable tablet, Cephalosporins, Developed, In vitro dissolution, Reference Listed Drug.

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Verma Ritesh, IJPRBS, 2015; Volume 4(5): 1-25



INTRODUCTION

GENERAL INTRODUCTION

Antimicrobial agents are among the most commonly used and misused of all drugs. The

inevitable consequence of the widespread use of antimicrobial agents has been the emergence

of antibiotic-resistant pathogens, feeling an ever-increasing need for new drugs. However, the

pace of antimicrobial drug development has slowed dramatically, with only a handful of new

agents, few of which are novel, being introduced into clinical practice each year. Reducing

inappropriate antibiotic use is thought to be the best way to control resistance. Although

awareness of the consequences of antibiotic misuse is increasing, overprescribing remains

widespread, driven largely by patient demand, time pressure on clinicians, and diagnostic

uncertainty. If the gains in the treatment of infectious diseases are to be preserved, clinicians

must be wiser and more selective in the use of antimicrobial agents.

This investigation reviews, discusses & offers a philosophical and a practical approach to the

appropriate use of antimicrobial agents and discusses the factors that influence the outcome of

such treatment. Also emphasized is the other aspects of antimicrobial agents owing to lack of

compliance of the patients generally Paediatrics & geriatrics population towards infection,

which can lead to super infection or drug resistance.

THE CEPHALOSPORINS

The antibiotics are useful and frequently prescribed antimicrobial agents that share a common

structure and mechanism of action ¾ inhibition of synthesis of the bacterial peptidoglycan cell

wall. The β-lactams also include the cephalosporin antibiotics, which are classified by

generation: First-generation agents have excellent gram-positive and modest gram-negative

activity; second-generation agents have somewhat better activity against gram-negative

organisms and include some agents with antianaerobe activity; third-generation agents have

activity against gram-positive organisms and much more activity against the

Enterobacteriaceae, with a subset active against P. aeruginosa; and fourth-generation agents

encompass the antimicrobial spectrum of all the third-generation agents and have increased

stability to hydrolysis by inducible chromosomal β -lactamases.

Bacterial resistance against the β-lactamantibiotics continues to increase at a dramatic rate.

Mechanisms of resistance include not only production of β-lactamases that destroy the

antibiotics but also alterations in or acquisition of novel penicillin-binding proteins and

decreased entry and/or active efflux of the antibiotic.



TASTE MASKING

Taste masking is defined as a perceived reduction of an undesirable taste that would otherwise

exist. Taste masking is also defined as a perceived reduction of an undesirable taste that would

otherwise/if exist. The ideal solution to reduce or inhibit bitterness is the discovery of a

universal inhibitor of all bitter tasting substances, which does not affect the other taste

modalities such as sweetness or saltiness Biologically, the perceptions of taste in humans occur

when molecules interacts with taste receptor on the tongue and trigger signals in the mouth

when they dissolve in saliva, which is sent to the brain area, where a specific taste sensation is

recognized. A molecule reacts with taste receptor with the help of small organs called taste

buds located in the mouth mainly on the surface of tongue and gives sensation like sweet, sour,

bitter and salty.

These four tastes are located on different receptors on tongue (fig 2), sensations for sweet are

located at tip of the tongue and sensations for sour are located at sides of the tongue whereas

bitterness at the back of the tongue and salty sensations are located at the sides and tip of the

tongue Recently, a basic taste umami has been discovered. Umami is the fifth independent

taste produced by monosodium glutamate (MSG) contained mainly in seaweed and disodium

inosinate (IMP) in meat and fish and others like aspartame etc. These above taste receptors

that bind to molecules down by saliva transmit electrical impulses by 7th, 9th and 10th cranial

nerves to these areas of brain which participate in perception of taste. This sensation result in

signal transduction from the receptor organs called taste buds which is having taste receptors.25

Human detects taste with taste receptor cells that are clustered in to onion‐shaped organs

called taste buds. Each taste bud has a pore that opens out to surface of the tongue enabling

molecules and ions taken into the mouth to reach the receptor cells inside. Human have around

10,000 taste buds and single taste bud contain 50‐100 taste cells.25

Chewable tablet16,17

Chewable tablet intended to disintegrate smoothly in mouth at a moderate rate either with or

without chewing. characteristically chewable tablets have a smooth texture upon

disintegration, are pleasant tasting and leave no bitter or no unpleasant taste. chewable tablets

one of the excellent alternative choices as an easy method of drug administration for these

patients. In fact, the FDA has invited pharmaceutical manufacturers to develop and produce

proper dosage forms especially for pediatric patients. Up until 1999, more than 60 chewable

tablet medications were approved for patient use in the U.S.A. The list includes a wide range of

medications such as analgesics, cold preparations, vitamins, anti-infectives, anti-convulsants

and antacids. In this context, chewable tablets are known to be advantageous over liquid



dosage forms in many aspects, such as higher palatability, better availability, stability, dose

precisions, portability and ease of administration especially during traveling.

Advantages of Immediate Release Tablets –

Economical and cost effective.

Quick onset of action.

Improved stability and bioavailability.

Provides some advantages of liquid dosage forms.

Adaptable to existing processing and packaging machinery.

Unique product differentiation.

Suitable for industrial production.

Material and Method

Formulation design

Formula for Preparation of Chewable Tablets of Cephalosporin's

In Formulation (F1,F2,F3), Direct Compression method was selected for tablet compression.

S.NO. INGREDIENTS F1 (Direct Compression)

1 API 227.52 mg 2 Perlitol (200 SD) 540.48 mg 3 Crosspovidone (XL -10) 70 mg 4 Aspartame 15 mg 5 Strawberry Flavor 10 mg 6 FDC red No 40 aluminium lake 1 mg 7 Magnesium stearate 6 mg Total weight of tablet 870 mg

FORMULA FOR PREPARATION OF F1 BY DIRECT COMPRESSION



BATCH SIZE – 500 TABLETS

Assay potency or Quantity of API per tablet (For API having d0.9=210.65µm) =

= 227.52 mg

Note: In F1, F2, F3, F4 API having (d0.9)=210.65 µm particle size was used.

In F1, poor flow of blend from hopper was observed due to micronized nature of API and low

particle size pearlitol i.e Pearlitol 200 SD. Therefore tablets were difficult to be compressed by

this method.

To overcome this problem, in F2, Pearlitol 500 DC and Aerosil were used to improve flow

property.

S.NO. INGREDIENTS F2 (Direct Compression)

F3 (Direct Compression)

1 API 227.52 mg 227.52 mg 2 Pearlitol (500 DC) 510.48 mg 500.48 mg 3 Crosspovidone (XL -10) 70 mg 70 mg 4 Aspartame 15 mg 15 mg 5 HPC LH 21 ---- 10 mg 6 Aerosil 30 mg 30 mg 7 Strawberry Flavor 10 mg 10 mg 8 FDC red No 40 aluminium lake 1 mg 1 mg 9 Magnesium sterate 6 mg 6 mg Total weight of tablet 870 mg 870 mg

FORMULA FOR PREPARATION OF F2 AND F3 BY DIRECT COMPRESSION

In F2, Capping was observed due to absence of binder in formulation. To overcome this

problem, HPC LH 21 was added as binder in formulation F3. Tablets were compressed and

checked for friability but friability test for tablets failed due to which further compression not

performed and tablets not given for dissolution.



Therefore due to above a problem, Direct Compression method was not choosen and Roller

Compaction method was selected for further formulations (F4-F9).

S.NO. INGREDIENTS F4 (Roller Compaction)

F5 (Roller Compaction)

Intragranular 1 API 227.52 mg 223.99 mg 2 Pearlitol (200 DC) 500.48 mg 504.01 mg 3 Crosspovidone (XL -10) 50 mg 50 mg 4 HPC LH-21 10 mg 10 mg 5 Aspartame 15 mg 15 mg Extragranular 6 Strawberry 10 mg 10 mg 7 FDC red No 40 aluminium lake 1 mg 1 mg 8 Crospovidone ( XL - 10) 20 mg 20 mg 9 Colloidal silicon dioxide (Aerosil 200) 30 mg 30 mg Lubrication 10 Magnesium sterate 6 mg 6 mg Total weight of tablet 870 mg 870 mg

FORMULA FOR PREPARATION OF F5 BY ROLLER COMPACTION


Assay potency or Quantity of API per tablet (For API having d90= 11.3µm) =

= 223.99 mg

In F4, same particle size API was used as used in Formulations F1-F3. Tablets were -compressed.

Dissolution of Tablets was performed in Official medium (pH 7.2 Phosphate Buffer). Dissolution

was very slow. So in F5, API having particle size d(0.9)-11 μm was used to check the effect of

particle size on dissolution by keeping same concentration of all functional excipients

(Disintegrant, Binder, Lubricant) and amount of API change due to assay potency was adjusted

in diluent quantity. Tablets were compressed and dissolution of tablets was performed. As a

result, dissolution was still very slow as compared to innovator but better than F4. So this

optimised particle size API was selected for further formulation devlopment.



As dissolution of F5 was very slow at both initial and end time points as compared to marketed

drug formulation (Innovator) in the dissolution medium. To improve dissolution, In F6, quantity

of crospovidone (Disintegrating agent) was increased in intragranular part. Dissolution

increased at end time points but was slow in initial time points.




Intragranular 1 API 223.99 mg 223.99 mg 223.99 mg 2 Perlitol (200 DC) 484.01 mg 474.01 mg 479.01 mg 3 Crosspovidone (XL -10) 70 mg 70 mg 70 mg 4 HPC LH-21 10 mg 10 mg 5 mg 5 Aspartame 15 mg 15 mg 15 mg Extragranular 6 Strawberry 10 mg 10 mg 10 mg 7 FDC red No 40 aluminium lake 1 mg 1 mg 1 mg 8 Crospovidone ( XL - 10) 20 mg 30 mg 30 mg 9 Colloidal silicon dioxide

(Aerosil 200) 30 mg 30 mg 30 mg

Lubrication 10 Magnesium sterate 6 mg 6 mg 6 mg Total weight of tablet 870mg 870 mg 870 mg

FORMULA FOR PREPARATION OF F6, F7, F8 BY ROLLER COMPACTION

Therefore in F7, quantity of crospovidone increased in extra granular part to increase

dissolution at initial time points. Dissolution was improved.

In F8, quantity of HPC LH 21 was decreased to decrease disintegration time of tablet and to

further improve dissolution. As a result disintegration time was decreased and increase in

dissolution was also observed. Hence dissolution profile of F8 was found to be very similar with

that of innovator in official medium (pH 7.2 Phosphate buffer).

Hence F8 was optimized and selected as final formula for further batches. Formulation F9 was

taken as scale up batch keeping same formula as that of F8.



FORMULAE FOR SCALE UP BATCH CHEWABLE TABLETS OF CEPHALOSPORINS

F9 (SCALE UP)


Intragranular 1 API 223.99 mg 2 Perlitol (200 DC) 479.01 mg 3 Crosspovidone (XL -10) 70 mg 4 HPC LH-21 5 mg 5 Aspartame 15 mg Extragranular 6 Strawberry 10 mg 7 FDC red No 40 aluminium lake 1 mg 8 Crospovidone ( XL - 10) 30 mg 8 Colloidal silicon dioxide (Aerosil 200) 30 mg Lbrication 8 Magnesium sterate 6 mg Total weight of tablet 870 mg

FORMULA FOR PREPARATION OF F9 BY ROLLER COMPACTION


Tablets were compressed, and dissolution test was performed. Dissolution profile of F8 tablets

were also was found to be matched with that of innovator in Official medium (pH 7.2

phosphate buffer).

Formulation Code

Bulk Density (g/cc)

Tapped Density (g/cc)

Carr’s Index (%) Hausner’s Ratio

F8 0.479 0.633 1.3215 24.32

EVALUATION OF PARAMETERS OF FINAL FORMULATION (F9)

RESULTS AND DISCUSSION

API CHARACTERISATION (PREFORMULATION STUDY)



Visual examination

Sr. No. Test Results

1. Appearance White to light yellow, crystalline powder

VISUAL EXAMINATION FOR COLOR OBSERVATION OF DRUG

Determination of absorption maxima (λmax) for analysis

The organic molecules in solution form, upon exposure to light in the ultra-violet region of the

spectrum, absorb light of particular wavelength depending on the type of electronic transition

associated with the absorption. API solution (20µg/ml) was scanned between 200-400 nm and

absorption maximum was determined spectrophotometrically. From the curve, λmax for Drug X

was found at 288 nm.

UV SPECTRUM OF DRUG X (λ MAX DETERMINATION)

Particle Size Distribution (PSD) Analysis of micronized drug

Particle Size Distribution (PSD) Analysis of micronized drug was performed using Malvern

Particle Size Analyser.



PARTICAL SIZE DISTRIBUTION SPECTRUM OF CEPHALOSPORIN

S .No. d value Particle size (µm)

1 D (90) 210.65 2 D (50) 150.50 3 D(10) 10.01

S .No. d value Particle size (µm)

1 D (90) 11.3 2 D (50) 4.0 3 D(10) 1.2



PARTICLE SIZE DISTRIBUTION VALUES FOR API SIZE (1)

CEPHALOSPORIN XRD Analysis

XRD SPECTRUM OF CEPHALOSPORIN

Assay and water by KF (%) Results

As according to vender COA and found within the specifications.

RESULT OF ASSAY AND WATER BY KF (%)

Flow properties determination of API

Test Results Specification mentioned in monograph API (d90-

210.65µm) API (d90-11µm)

Assay 100.1 100.0 95.0-103.0 Water by KF(%w/w) 10.8 10.8 9.0- 12 % w/w

Test Results

API (d0.9-210.65µm) API (d0.9-11µm) Bulk density 0.174 0.1695 Tapped Density 0.275 0.2710 Compressibility index 36.72 37.45 Hausner Ratio 1.5804 1.598



FLOW PROPERTIES OF API

Solubility of cephalosporin (Selected optimised particle sized) API in various solvents and

media

Sr. No. Solvents and buffer Results

1. Acetonitrile Very soluble 2. Methanol Very soluble 3. Anhydrous ethanol Freely soluble 4. Glycine buffer (pH 3.0) 0.040 mg/ml 5. Acetate buffer (pH 4.5) 0.36 mg/ml 6. Phosphate (pH 6.8) 0.42 mg/ml

7. Phosphate (pH 7.2) 0.52 mg/ml

SOLUBILITY OF OPTIMIZED PARTICLE SIZE API

Standard curve of Cephalosporin (optimised particle sized API)

The standard plot was prepared by taking concentration on x-axis and the absorbance on y-axis.

The calibration equation for straight line was obtained.

Level Concentration (µg/ml) Absorbance Average absorbance Replicate-I Replicate-II

0% 0.00 0.000 0.000 0.000

10% 1.82 0.055 0.057 0.056

20% 3.64 0.115 0.115 0.115

40% 7.28 0.223 0.223 0.223

60% 10.91 0.335 0.335 0.335

80% 14.55 0.441 0.440 0.441

100% 18.19 0.537 0.538 0.538

Y-intercept 0.0095

Slope 0.0292

Square of correlation coefficient(R²) 0.9994

Residual sum of square 0.00061



ABSORBANCE VERSUS CONCENTRATION VALUES

STANDARD CURVE OF CEPHALOSPORIN

FOURIER TRANSFORMS Infrared Spectroscopy (FTIR) studies

FTIR of optimized particle size API was performed using KBr disc method.

STANDARD SPECTRA OF CEPHALOSPORIN AS PER USP NF 32

FTIR SPECTRUM OF CEPHALOSPORIN

Note: Optimisation of particle size was done on basis of dissolution results of the

formulation.

y = 0.0298x + 0.0042 R² = 0.9994

0

0.1

0.2

0.3

0.4

0.5

0.6

0 5 10 15 20

Ab

sorb

ance

Concentration (µg/ml)

Standard curve of drug in pH 7.2 phosphate buffer

Average absorbance

Linear (Average absorbance)



DRUG-EXCIPIENT COMPATIBILITY STUDIES

The compatibility of drug and formulation components is important prerequisite before

formulation. It is therefore necessary to confirm that the drug does not react with the polymers

and excipients under experimental conditions and affect the shelf life of product or any other

unwanted effects on the formulation.

Procedure:

Drug and excipient were thoroughly mixed. For these mixtures of API with excipients were

added and loaded in glass vials. These vials are exposed to 40˚C/75%RH for 4

weeks. Observations for physical appearance are made at initial, 2 weeks and 4weeks, the

samples were withdrawn for analysis.

Sr. No.

Drug + Excipient API: Expt

Initial Observtion (Color)

Final observation Conclusion

2nd week (Color)

4th week (Color)

1. Drug X (API) N/A light yellow light yellow light yellow Compatible 2. Drug X + Mannitol

(200 SD) 1:1 White to

light yellow White to light yellow

White to light yellow

Compatible

3. Drug X + Aspartame

1:0.5 White to light yellow



Compatible

4. Drug X + L-HPC 1:1 White to light yellow



Compatible

5. Drug X + Crospovidone




Compatible

6. Drug X + Lactose monohydrate

1:1 White to light yellow



Incompatible

7. Drug X + Magnesium stearate




Compatible

8. Drug X + Aerosil 1:0.05 White to light yellow



Compatible

9 Drug X + FDC Red 1:0.25 Light pink Light pink Light pink Compatible 10 Drug X +

Strawberry 1:.05 Light yellow Light yellow Light yellow Compatible

RESULTS OF COMPATIBILITY STUDY

As drug incompatibility (change in color) was observed with Lactose monohydrate therefore

Lactose monohydrate was not used in the formulation.



Sr. No. Drug + Excipient Assay (% w/w) Initial

Assay (% w/w) 1 month open

Related Substance (% w/w) Initial

Related Substance (% w/w) 1 month open

1. Drug X (API) 98.62 97.96 3.23 4.12 2. Drug X + Mannitol

(200 SD) 94.59 90.73 1.69 1.93

3. Drug X + Aspartame 94.73 90.69 3.00 3.14 4. Drug X + L-HPC 21 94.54 94.02 1.55 1.99 5. Drug X +

Crospovidone 94.03 91.69 1.59 3.18

6. Drug X + Magnesium stearate

97.11 93.69 3.20 4.13

7. Drug X + Aerosil 96.69 92.54 1.60 2.08 8. Drug X + FDC Red 97.18 95.61 1.50 1.91 9. Drug X + Strawberry 98.94 95.32 1.71 1.94

RESULTS OF COMPATIBILITY STUDY

FORMULATION TESTING

Formulation Development

Direct Compression method

In F1- Poor flow of blend from hopper was observed due to micronized nature of API and low

particle size pearlitol i.e Pearlitol 200 SD. Therefore tablets were difficult to be compressed by

this method.

To overcome this problem, in F2, Pearlitol 500 DC and Aerosil was used to improve flow

property.

In F2- Capping was observed due to absence of binder in formulation. To overcome this

problem, HPC LH 21 was added as binder in formulation F3.

In F3- Tablets were compressed and checked for friability but friability test for tablets failed due

to which further compression not performed and tablets not given for dissolution.

Therefore due to above problems, Direct Compression method was not choosen and Roller

Compaction method was selected for further formulations (F4-F9).

In F4 and F5, particle size optimization and selection of particle size was done to check effect on

dissolution. In F4, API having d (0.9)-210.60 µm particle size was used as used in F1 and F2. As in



F5, API having particle size d(0.9)-11 µm was used, dissolution was better than that of F4.

Therefore for further formulation development this optimized particle size d (0.9)-11 µm was

selected for further formulation.

In F5, disintegrating agent crospovidone added in extra granular part increased dissolution at

initial time points.

In F6, disintegrating agent crospovidone added in intragranular part increased dissolution at

end time points.

In F7, disintegrating agent crospovidone added in extra granular part as compared to F5

increased dissolution at initial time points.

In F8, added amount of Hydroxy propyle cellulose (LH-21) decreased, decreased disintegration

time and further increased dissolution. Dissolution profile of F8 tablets was found to be similar

with innovator.

In F9, dissolution profile of tablets also found to be similar with innovator.

Evaluation of tablets

Formulation Code

Weight Variation

Friability (%) Thickness (mm)

Hardness (kp)

Disintegration Time

F3 Passed 0.210 4.40-4.56 7.2-8.3 35 sec - 45 sec F4 Passed 0.198 4.26-4.48 7.4-8.1 45 sec - 56 sec F5 Passed 0.223 4.50-4.40 7.0-8.5 40 sec - 45 sec F6 Passed 0.321 4.40-4.55 7.0-8.1 39 sec - 42 sec F7 Passed 0.305 4.73-4.90 7.0-8.2 25sec - 30sec F8 Passed 0.279 4.80-4.90 7.4-8.3 35 sec - 45 sec F9 Passed 0.298 4.75-4.85 7.4-8.1 35 sec - 45 sec

EVALUATION OF TABLETS OF ALL FORMULATIONS

Formulation Code Thickness(mm) Disintegration time Assay (%)

F8 4.80-4.90 35 sec - 45 sec 100.2 F9 4.75-4.85 35 sec - 45 sec 98.5



EVALUATION OF TABLETS OF FINAL FORMULATIONS F7 AND F8

Drug formulations were tested for Dissolution as shown below.

Dissolution test condition

Name of drug Drug X

Dissolution apparatus USP Type II (paddle) Temperature 37 °C ± 0.5 Paddle speed 25 Rpm Volume of dissolution medium 900 ml Dissolution medium pH 7.2, phosphate buffer (0.05M) Sampling profile (minutes) 10, 15, 20, 30, 45 min.

DISSOLUTION TEST CONDITION

Every time the volume of sample withdrawn, was replaced by fresh dissolution medium

maintained at the same temperature. The sample removed was diluted and absorbance was

taken.

Comparative dissolution profile of various formulations with Innovator in pH 7.5 phosphate

buffer medium.

Time (in min.)

Innovator (% CDR)

F3 (% CDR)

F4 (% CDR)

F5 (% CDR)

F6 (% CDR)

F7 (% CDR)

F8 (% CDR)

0 0 0 0 0 0 0 0 10 65 30 49 40 42 52 61 15 85 43 59 64 68 70 83 20 94 52 67 70 80 86 95 30 99 69 77 97 98 100 100 45 102 77 80 98 99 101 101



COMPARATIVE DISSOLUTION PROFILE IN VARIOUS FORMULATION PH 7.2 PHOSPHATE

BUFFER MEDIUM

COMPARATIVE DISSOLUTION PROFILE IN VARIOUS FORMULATION PH 7.2 PHOSPHATE

BUFFER MEDIUM.

F2 value for best formulation (F8) - 71

Comparative dissolution profile of final formulations F7 and F8 tablets with Innovator in pH

7.2 phosphate buffer medium.

Time (in min.) Innovator (% CDR) F8 (%CDR) F9 (%CDR)

0 0 0 0 10 65 60 61 15 85 82 83 20 94 93 95 30 99 100 100 45 102 101 101 Similarty factor (f2) Value 69 71

0

20

40

60

80

100

120

0 10 20 30 40 50

% C

DR

Time ( in minute)

Comparative Dissolution profile in pH 7.2 Phosphate buffer

F3 (% CDR)

F4 (% CDR)

F5 (% CDR)

F6 (% CDR)

F7 (% CDR)

F8 (% CDR)



COMPARATIVE BETWEEN F7, F8 TABLET WITH INNOVATOR

COMPARATIVE DISSOLUTION PROFILE IN PH 7.2 PHOSPHATE BUFFER MEDIUM.

Stability data of Final Formulation (F9) at accelerated conditions (40º C±2/75%±5 RH) at 3

months

Sr. No.

Test Specifications Initial (RT)

After 1 month (40ºC/75%RH)

After 2 Months (40ºC/75%RH)

After 3 Months (40ºC/75%RH)

1 Description Pink colour , round shaped, smooth tablets, debossed with ‘C13’ on one side and plain on other side

Complies Complies Complies Complies

2 Assay (By HPLC) (%)

90-110 98.5 97.8 97.1 96.9

3 Dissolution (in pH 7.2 phosphate buffer)

NLT 75 % Q at 45 minutes

99 101 102 101

0

20

40

60

80

100

120

0 10 20 30 40 50

% C

DR

Time ( in minute)

Comparative Dissolution profile in pH 7.2 Phosphate buffer

Innovator (% CDR)

F8 (%CDR)

F9 (%CDR)



PHYSICAL AND CHEMICAL PARAMETER ANALYSIS BEFORE AND AFTER ACCELERATED

STABILITY STUDY (40º C±2/75%±5 RH).

Tablets were found to be stable as all the physical and chemical properties were found within

limits mention in monograph.

Hence Formulation, development, evaluation of stable and bioequivalent chewable tablet was

attained.

CONCLUSION

The aim was to develop a stable chewable tablet of cephalosporin’s whose in-vitro dissolution

profile is similar or to the nearby with that of marketed dosage form, so that a dosage form

having same therapeutic efficacy at a low cost can be available in the market.

As cephalosporin has poor dissolution property. Therefore dissolution was improved by using

micronized API, binder, disintegrate in the formulation.

Preformulation study was performed. In-vitro parameters of formulations were evaluated. As

according to USFDA guideline, similarity factor (f2) value should be between 50-100 in official

medium. Therefore Formulation F8 was selected as best formulation as its dissolution profile

was found to be similar (On basis of similarity factor f2 value 66) with that of Innovator in

official medium (pH 7.2 phosphate buffer medium). Tablets dissolution was performed.

Dissolution profile of F8 tablets also was found to be similar with that of innovator.

It was optimised and Scale up (F9). Dissolution profile of F9 tablets was also found to be similar

in pH 7.2 phosphate buffer medium (Similarity factor f2 value 63). Stability studies of final batch

F9 (after packing) were performed and the product was found stable. Thus objective of

Formulation, development and evaluation of a stable and bioequivalent chewable tablet was

attained.

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