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81 Nagamani D. et al. / International Journal of Biopharmaceutics. 2015; 6(2): 81-92.

e- ISSN 0976 - 1047

Print ISSN 2229 - 7499

International Journal of Biopharmaceutics

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FORMULATION AND EVALUATION OF CHLORPHENIRAMINE

MALEATE EXTENDED RELEASE TABLETS BY USING DIRECT

COMPRESSION TECHNIQUE

Nagamani D*1, Ramesh Y

1, Saravanankumar K

2, Gnanaprakash K

1, Gobinath M

1

1Department of Pharmaceutics, Ratnam Institute of Pharmacy, Pidathapolur (V & P), Muthukur (M), SPSR Nellore (Dist)-

524346, Andhra Pradesh., India 2Department of Pharmaceutics, Sri Vidhyanikethan College of Pharmacy, A.Rangampet, Chandragiri Mandal, Tirupati,

Chittoor (Dist) -517102, Andhra Pradesh, India.

ABSTRACT

The objective of present investigation is to formulate and evaluate Chlorpheniramine maleate extended release

tablets with different ratios of polymers Micro crystalline cellulose HPMC K4M, HPMC 6CPS, PEG 6000 by using direct

compression technique The pure drug (CPM) and polymers were obtained from Drug India, Hyderabad. Accurately weigh

pure drug and mix with different ratios of polymers and passed through sieve for complete mixing and the powder weigh for

the individual tablet and compressed. Prepared tablets were evaluated for incompatibility studies of FT-IR and DSC and

Post-formulation parameters concluded that there should be certain amount of strength and resistance to friability for the

tablet. The hardness of chlorpheniramine maleate extended release tablet ranges from 7.8 to 8.7 kg/cm3. Friability ranges

from 0.157 % to 0.214%. In-vitro dissolution studies of best formulation obtained as the drug release 99.1% at 7 Hrs

duration of time as compared with dissolution profile of marketed sample. Based on In-vitro drug release studies the data

were fitted into Kinetic modeling and the best formulation CPM-9 has been showed by graphs as different kinetic models

plots of Zero-order, First order, Higuchi. Korse Meyer- Pappas and Hixson Crow well. The stability studies were

represented for best formulation CPM-9 as compared with marketed sample.

Key words: Chlorpheniramine maleate, Extended release, Higuchi, Hixson Crowell Korse Meyer Pappas.

INTRODUCTION

An extended release dosage form extends the

life of a drug then the dosage regimen shifts from 3 times

a day to once or twice a day. To the successful

formulation of a delayed release device requires a

comprehensive understanding of the mechanism of drug

release from the macroscopic effects of size, shape and

structure through chemistry and molecular interaction.

The dosage form relates to multi particulate shows less

Corresponding Author

Nagamani D E-mail: [email protected]

prone to food effects than monolithic and is often the

preferred formulation for delayed release and/ or

extended release. The conventional method used for

formulation of extended release products produced as

compressed tablets. The method for extended release

tablet dosage form involves, an active ingredient is

conventionally compounded with cellulose ethers like

methylcellulose, ethyl cellulose or hydroxyl propyl

methylcellulose with or without adjuncts and the

resulting mixture is pressed into tablets. (Malty T et al.,

2014)

Extended release dosage form is one of the drug

products categorized under the term modified release

IJB


dosage forms (FDA, 1997). It refers to the products,

which are formulated to make the drug available over an

extended period after ingestion: thus, it allows a

reduction in dosing frequency compared to a

conventional type i.e., immediate release (IR) dosage

form. (Bhargavi P et al., 2013). Extended release drug

delivery system consists of the drug is absorbed over a

longer period of time or the system which shows a slow

release of the drug over an extended period of time.

Initially, the extended release dosage form releases an

adequate amount of drug to get necessary blood

concentration (loading dose, DL) for therapeutic response

and further amount of drug releases at a controlled rate

(maintenance dose, DM) to maintain the blood levels for

some desirable period of time.(Madhusudhan P et al.,

2010)

Recently, the pharmaceutical products of

extended release tablets became very useful tool in

medical field for practice. It offers a wide range of actual

and perceived advantages to the patients. An extended

release product also provides promising way to decrease

the side effects of drug by reducing the fluctuation of the

therapeutic concentration of drug in body. Oral extended

release drug delivery medication accounts for the largest

share of drug delivery systems. The extended release

products will optimize therapy and safety of drug and

improves the patient convenience and compliance. (Patel

Kundan.K K et al., 2012)

Chlorpheniramine extended release tablets

were prepared using direct compression technique and

evaluated. Chlorpheniramine is an anti cholinergic

antihistamine. It is also effective against nausea and

motion sickness, with its primary mechanism of action

being its ability to reduce acetylcholine levels in the

brain. The recommended daily dosage of

Chlorpheniramine is 12 mg. The apparent steady- state

volume of distribution is 2.5-3.2 L/kg and is about 70%

bound to plasma proteins. The chlorpheniramine maleate

is metabolized in the liver and it is expressed as hepatic

CYP2D6 enzymes.

MATERIALS AND METHODS The pure drug of chlorpheniramine maleate was

obtained from Drug India, Hyderabad and excipients like

MCC, HPMC K4M, HPMC 6CPS,PEG 6000 were

obtained from Drug India, Hyderabad.

Method used

The core tablets (average weight 500mg) of

chlorpheniramine maleate were prepared by direct

compression method. The composition of tablet core is

shown in table- . The various ratios of excipients Micro

crystalline cellulose, sodium dihydrogen phosphate di

hydrate, HPMC K4M, HPMC 6CPS, PEG6000 (extended

release polymers) were used for formulation. The

ingredients were weighed, mixed and passed through a

sieve to ensure complete mixing. Then the tablets were

prepared by compressing thoroughly the mixed materials

using 13mm round, flat, punches on 16 station tablet

punching machine (Cad mach).

EVALUATION

Drug-Excipient compatibility studies

Fourier transformer infrared spectroscopy

FT-IR patterns were studied by shimadzu

8400S, Japan FT-IR spectrophotometer. The samples of

chlorpheniramine maleate (drug) were previously ground

and mixed thoroughly with potassium bromide, an infra

red transparent matrix, at 1:5 (Sample: KBr) ratio,

respectively. Then subjected for scanning from 4000cm-1

to 400cm-1

using FTIR spectrophotometer.

B. Differential scanning calorimetry

Approximately 4 mg of drug, chlorpheniramine

maleate+excipients were taken in aluminum pan, sealed

with aluminum cap and kept under nitrogen purging

(atmosphere). Both the samples were scanned from 300-

3000

with the scanning rate of 50C rise/min using

differential scanning calorimetry.

Micro meritic properties

Angle of Repose

The angle of repose or the critical angle of

repose, of a granular material is the steepest angle of

repose or dip of the slope relative to the horizontal plane

when material on the slope face is on the verge of sliding.

This angle is in the range of 00-90

0.

The angle of repose was calculated by following formula

tan θ = h/r

θ = tan-1

h/r

Where, θ = angle of repose, h= Height of heap,

r= Radius of heap.

Bulk Density

The bulk density of a powder is the ratio of the

mass of an untapped powder sample and its volume

including the concentration of the inter particulate void

volume.

Bulk density= Weight of powder/ Bulk volume

Tapped Density

The tapped density is an increased bulk density

attained after mechanically tapping a container

containing the powder sample. After measuring the bulk

volume the same measuring cylinder was set into tap

density apparatus. The tapped density is calculated by the

following formula

Tapped density = Weight of powder/ Tapped volume

Carr’s Index [Compressibility index]

It is one of the most important parameter to

characteristic the nature of powders and granules. It can

be calculated from the following equation:


Carr’s index = Tapped density- Bulk density/ Tapped

density× 100

Hausner’s ratio

Hausner’s ratio is an important character to

determine the flow property of powder and granules. This

can be calculated by the following formula

Hausner’s ratio [HR] = Tapped density/ Bulk density

HR<1.25 – indicates good flow property

HR>1.25 – indicates poor flow property.

Post compression parameters The prepared chlorpheniramine maleate

extended release tablets were evaluated for following

parameters.

Weight variation

Twenty tablets of each formulation were

selected at random and weighed individually. The weight

of individual tablet was noted. Average weight was

calculated from the total weight of the tablets. The

individual weight was compared with average weight.

The weight of not more than two tablets should deviate

from the average weight by more than the percentage

deviation allowed and none should deviate by double the

percentage deviation. The percentage deviation was

calculated by using the formula. (Lachman L. 1987).

Percentage deviation = Individual weight –Average

weight × 100

Average weight

Thickness Variation

Ten tablets from each formulation were taken

randomly and their thickness was measured with a digital

vernier caliper. Average thickness and standard deviation

were calculated.

Hardness

Hardness (diametric crushing strength) is the

force required to break a tablet across the diameter. The

tablet is placed across the diameter in between the

spindle and anvil. The knob is adjusted to hold the tablet

in position. The pressure is increased slowly to break the

tablet. For each formulation, the hardness of 5 tablets was

determined using a Monsanto hardness tester, mean and

SD were calculated.

Friability

The friability of a sample of 20 tablets was

measured utilizing an Electro lab, Friability tester USP

23. Pre – weighed tablets were placed in a plastic

chambered friabilator attached to a motor revolving at a

speed of 25 rpm for 4 min. The tablets were then de –

dusted, reweighed, and percentage weight loss (friability)

was calculated.

Friability = (W1 – W2) × 100

W1

Where, W1= Initial weight of tablet and W2= Final

weight of tablet

Determination of drug content

Two tablets from each formulation were crushed

to powder. Crushed powder were transferred into 100 ml

flask and diluted to 100 ml with 0.1N HCL solution and

stirred magnetically for 1 hr, centrifuged and filtered. 1ml

of this solution was taken and it was diluted to 100 ml

with 0.1N HCL and then absorbance was noted at 261

nm using UV- Visible spectrophotometer. Using

calibration curve the drug content was determined from

absorbance of tablets.

In vitro dissolution studies

The studies were done using USP dissolution

apparatus II (Lab India). This test was performed by one

tablet from each formulation using 900ml of phosphate

buffer 6.8 at 370C temperature and 50 rpm. Every one

hour intervals are taken 5ml sample from each

dissolution medium and simultaneously replaced with

fresh dissolution medium. Then the samples were

analyzed Spectra photo metrically at 261nm. The

percentage drug released at time interval was calculated

and plotted against time. The cumulative percentage of

drug release was calculated.

Mathematical modeling for Drug Release Profile

The cumulative amount of chlorpheniramine

maleate released from the formulated tablets at different

time intervals were fitted in to several kinetic models

such as Zero order kinetics, first order kinetics, Higuchi

model and Korse Mayer Pappas model to characterize

mechanism of drug release.

STABILITY STUDIES

Accelerated stability studies for

chlorpheniramine maleate extended release tablets was

carried out as per ICH guideline ‘Q1E Evaluation for

stability Data’ using Ostwald stability chamber for best

formulation the stability study was carried out at room

temperature as well as different accelerated temperature

and humidity conditions for a period of three months.

The conditions were modified as 250C/60%RH,

400C/70%RH, 60

0C/80%RH for every two months i.e.,

initial, 1st month and 2

nd month respectively.

Ten tablets were individually wrapped using

aluminum foil and packed in amber colored screw cap

bottle and kept at above specified conditions in stability

chamber for three months. Tablet samples were evaluated

for initial, 1st month and 2

nd month for drug content as

well as subjected for In vitro drug release study.

RESULTS AND DISCUSSION

Drug-excipient compatibility study


Differential scanning calorimetry

The DSC spectra of sample (pure drug), the exothermic

peak was 122.50C and also -10.65mw.

The DSC spectra of sample code CM2 containing

drug+mcc+HPMCK4M, the exothermic peak was 72.70C

and also 3590C it lies between -4.387mw to -5.950mw.

The DSC spectra of sample code CM3

containing drug+HPMC6CPS+PEG6000, the exothermic

peak was 121.90C and -9.29mw and endothermic peak

was 286.20C and -7.50mw.The CM1 and CM3 DSC

spectra samples exhibits there is no incompatibility in

their regions of 121.90C and 122.5

0C.

The DSC spectra of sample code CM4

containing drug+MCC+HPMC K4M+HPM C6CPS+PE

G6000, the exothermic peak was 64.70C and endothermic

peak was 287.50C.

The sample CM3 and CM4 of DSC spectra, the

exothermic peak 62.60C and 64.70C, the endothermic

peak 286.20C to 287.5

0C there is no incompatibility. As

shown in figure no11 and 12. And also shown in Table

column table no. 9.

Table 1. Formulation table for chlorpheniramine maleate Extended release tablets

Formulation in

Ratios(mg) CPM1 CPM2 CPM3 CPM4 CPM5 CPM6 CPM7 CPM8 CPM9

Drug 12 12 12 12 12 12 12 12 12

MCC 175 175 175 175 175 175 175 175 175

NaHPO2 85 85 85 85 85 85 85 85 85

HPMC K4M -- -- -- 104.5 102.5 99 96.5 95.5 95

HPMC 6CPS 125 111 106.5 -- -- -- 90.5 91.5 92

PEG 6000 62 76 80.5 82.5 84.5 88 -- -- --

Talc 15 15 15 15 15 15 15 15 15

Magnesium

stearate 26 26 26 26 26 26 26 26 26

Drug-chlorpheniramine maleate (CPM) , MCC- microcrystalline cellulose, NaHPO2 sodium dihydrogen phosphate

dehydrate, HPMC- Hydroxypropyl methyl cellulose, PEG- polyethylene glycol

Table 2. Interpretation data for FTIR Spectra of chlorpheniramine maleate

IR absorption bands (cm-1

) Bond Functional group

Observed peak Characteristic peak

3566,3527,3427,

3408,3375,3348,

3336,3325,3273,3267,3246,3234,3086,3066,3055

3300-3500

3200-3400

3010-3100

C-H stretch

N-H stretch

=C-H Stretch

Alkanes

10 Amines

Alkenes

2872,2411,2324,2247,2225,2150 2100-2660 -C=C- Alkynes

1452,1431,1409 1400-1500

1550-1300 CH2-Scissoring Amides

Table 3. Interpretation data for FTIR Spectra of micro crystalline cellulose

Table 4. Interpretation data for FTIR Spectra of HPMC K4M




3462,3446,3367,3348,31903170,31

53,3126 3500-3100 0-H stretch H- bonded alcohols, phenols

2924,2875,2854,2760,2746

3300-2500

3100-3000

3100-3000

(M)O-H stretch,

(s) C-H stretch

Carboxylic acids,

Aromatics




1330.88 1360-1290 N-O asymmetric stretch Nitro compounds

1122.57 1250-1020 C-N stretch Aliphatic amines

975.98 950-910 O-H bend Carboxylic acids

848.68 900-675 C-H Aromatics


1444,1307 1500-1400 (m) C-C stretch(

in- ring Aromatics

948,839,808,754

1000-650

900-675

910-665

850-550

(s)= C-H bend

(s) C-H ”00p”

(s,b) N-H wag

(m) C-Cl Stretch

Alkenes

Aromatic

10,2

0 amines

Alkyl halides

Table 5. Interpretation data for FTIR Spectra of PEG 6000




2875,2860,

2800,2697 2900-2695 C-H stretching Alkanes

1242 1200-1250 =C-H bend Alkyne

956,945,

898,842

950-900

975-780

O-H bending

(out of plane)

-C=H bending

Phenol

Alkenes

551.6 < 900 C-H bending Alkane

Table 6. Interpretation data for FTIR Spectra of chlorpheniramine maleate + HPMC K4M




3483,3375,3350,

3315,3290,3275 3500-3200 O-H stretch

H- bonded alcohols,

phenols

3032,3012 3100-3000

3100-3000

C-H stretch

=C-H stretch Aromatic alkenes

1357,1332,1319 1360-1290 N-0 symmetric stretch Nitro compounds

781,763,754 1000-650

910-665

=C-H bend

N-H wag

Alkenes

10, 2

0 amines

Table 7. Interpretation data for FTIR Spectra of chlorpheniramine maleate+ PEG 6000




3462,3407,3377,

3367,3352,3300,3282

3500-3250

3400-3250

O-H stretch

N-H Stretch

Phenols,

10 amides

2924,2853,2815,2777,2754,2644 3300-2500

3400-3250

O-H stretching

N-H stretch

Carboxylic acids,

10, 2

0 amides, amines

1670.35 1760-1665

1680-1640

C=O stretch

-C=C- stretch

Carbonyls, α,β unsaturated

ketones

1273,1107,1095 1330-1100 C-N stretch Aromatic amines

Table 8. Interpretation data for FTIR Spectra of chlorpheniramine maleate+MCC+HPMC K4M




3367,3342,3304

3275,3228

3400-3250

3300-3270

N-H stretch

C-H stretch 1

0 amines, amides, alkenes

1632.6 1650-1580 N-H bend 10 amines

1400.32 1550-1475 N-O asymmetric stretch Nitro compounds

1357,1332, 1261,

1370-1350

1335-1250

C-H rock

C-N stretch

Alkanes

Aromatic amines

Table 9. Interpretation data for FTIR Spectra of chlorpheniramine maleate+MCC+HPMC K4M+HPMC

6CPS+PEG 6000





3628,3599,3396,

3383,3367,3298

3238

3650-3250

3400-3200

O-H stretch

N-H stretch

Carboxylic acids, 10, 2

0

amides

1585,4 1650-1580

1600-1585

N-H bend

C-C stretch( in-ring) 1

0 Amines, Aromatics

1413,1400 1550-1475

1500-1400

N-O asymmetric stretch

C-C stretch(in-ring)

Nitro compounds

Aromatics

999.1,950.1,873 1000-650 =C-H bend Alkenes

Table 10. Data of DSC SPETRAS of SAMPLES

Pre compression (micro meritic) parameters for chlorpheniramine maleate extended release tablets

Table 11. Micro meritic parameters

F.code

Derived properties Flow properties

Bulk density

(mean±SD)

(g/cm3)

Tapped density

(mean±SD)

(g/cm3)

Angle of repose

(mean±SD)

(Degree)

Carr’s index

(mean±SD)

(%)

Hausner’s ratio

(mean± SD)

(%)

CPM-1 0.373 0.497 0.567 24.94 1.332

CPM-2 0.378 0.520 0.542 27.30 1.375

CPM-3 0.370 0.512 0.523 27.73 1.383

CPM-4 0.377 0.526 0.542 28.32 1.395

CPM-5 0.363 0.515 0.567 29.51 1.418

CPM-6 0.367 0.534 0.523 31.27 1.455

CPM-7 0.384 0.543 0.542 29.28 1.414

CPM-8 0.371 0.520 0.567 28.65 1.401

CPM-9 0.363 0.512 0.523 29.10 1.410

Post compression parameters for Chlorpheniramine maleate extended release tablets:

Table 12. Results of physicochemical parameters of all formulations

F. Code

Thickness

Mean SD

(mm)

Hardness

Mean SD

(kg/cm3)

Friability

Mean SD

(%)

Weight variation

Mean SD

(mg)

Drug content

Mean SD

CPM-1 3.22 8.3 0.159 497±0.4 98.3±0.5

CPM-2 3.35 8.7 0.167 498±0.5 98.5±0.2

CPM-3 3.48 7.8 0.214 499±0.2 99.2±0.5

CPM-4 3.52 8.5 0.157 497±0.4 96.4±0.6

CPM-5 3.48 8.3 0.115 496±0.5 97.3±0.7

CPM-6 3.37 8.5 0.156 493±0.2 99.2±0.6

CPM-7 3.35 7.9 0.167 497±0.4 99.4±0.5

CPM-8 3.52 8.3 0.146 496±0.5 98.7±0.6

CPM-9 3.48 7.8 0.157 498±0.4 98.3±0.7

In-vitro Drug release studies of chlorpheniramine maleate extended release tablets:

Table 13. In- vitro drug release profile of chlorpheniramine maleate extended release tablets

Time

(hrs)

Cumulative % drug release

CPM-1 CPM-2 CPM-3 CPM-4 CPM-5

1 10.2 10.6 11.1 11.3 11.7

2 16.5 17.4 23.4 25.3 29.1

F.code Exothermic Endothermic

CM1 122.50C -10.65mw --

CM2 72.70C -4.387mw --

CM3 121.90C -9.29mw 286.20C -7.50mw

CM4 64.70C -3.786mw 287.50C -7.85mw


3 29.3 30.2 31.1 35.4 39.7

4 38.1 39.7 43.3 47.5 50.7

5 48.6 50.9 55.4 57.6 63.1

6 57.6 66.6 68.4 70.1 70.5

7 75.6 77.4 79.2 79.9 80.8

8 84.9 86.4 86.7 87.1 88.2

9 97.2 98.6 97.5 98.8 98.6

Table 14. In-vitro drug release profile of chlorpheniramine maleate ER tablets of formulation CPM-6 to CPM-9 &

marketed sample

Time

(hrs)

Cumulative % drug release

CPM-6 CPM-7 CPM-8 CPM-9 Innovator brand name: (Chlorphen-12)

1 12.7 13.1 14.2 15.1 15.8

2 30.9 35.4 37.8 43.2 45.7

3 46.8 48.6 50.7 53.4 54.8

4 57.6 59.2 59.5 62.6 63.1

5 64.4 64.9 65.7 70.6 71.2

6 71.6 71.8 73.8 78.1 79.3

7 81 82.4 84.9 85.1 85.6

8 88.3 88.9 89.1 89.2 89.4

9 98.8 98.6 98.8 99.1 99.7

KINETIC MODELLING

Table 15. Parameters and determination coefficients of release profile from Chlorpheniramine maleate extended

release tablets

STABILIY STUDIES

Table 16. Physical evaluation of tablet blend and tablets of optimization of stability formulations

The samples analyzed at initial stage and after one month and after two months at accelerated stage.

Table 17. Samples analyzed at initial, 1 month and two months

F.code Zero order First order Higuchi

Korse Meyer

Pappas Hixson

R2 M R

2 M R

2 M R

2 M R

2 M

CPM 1 0.993 -32.30 0.781 -0.359 0.881 -62.31 0.988 0.972 0.979 0.611

CPM 2 0.996 -26.26 0.695 0.4001 0.978 -37.89 0.406 0.723 0.972 0.628

CPM 3 0.997 2.783 0.822 0.375 0.987 -33.03 0.906 1.287 0.959 0.636

CPM 4 0.997 22.09 0.756 0.431 0.995 3106.0 0.990 0.938 0.943 0.641

CPM 5 0.989 48.96 0.864 0.355 0.998 -2768.6 0.985 1.096 0.915 0.646

CPM 6 0.973 79.28 0.77 0.413 0.993 -2350.2 0.971 1.113 0.880 0.641

CPM 7 0.964 95.84 0.792 0.399 0.988 -2105.3 0.95 1.104 0.861 0.634

CPM 8 0.958 108.78 0.792 0.411 0.978 -3708.9 0.945 1.089 0.856 0.632

CPM 9 0.934 136.1 0.795 0.408 0.972 -1640.8 0.928 1.105 0.818 0.622

cumulative % drug release ( Best

Formulation code CPM 9)

cumulative % drug release ( Innovator

Brand Name: Chlorphen-12 )

Time (Hr) Initial One month Two

months Initial

One

month

Two

months

1 11 13 12 15 16 14

4 31 33 35 34 35 37

8 54 57 52 56 59 55

20 89 91 87 91 97 89

Parameters Initial One month Two months

Color Cream or White Cream or White Cream or White


Fig 1. FT-IR Spectra of Chlorpheniramine maleate (pure drug)

Fig 2. FT-IR Spectra of Micro crystalline cellulose

Surface Smooth Smooth Smooth

Thickness 3.3-3.4 3.3-3.4 3.3-3.4

Hardness 4 4 4

Assay 99.3 100.6 99.5


Fig 3. FT-IR Spectra of HPMC K4M

Fig 4. FT-IR Spectra of PEG 6000

Fig 5. FTIR Spectra of chlorpheniramine maleate + HPMC K4M


Fig 6. FT-IR Spectra of Chlorpheniramine maleate (pure drug)+PEG 6000

Fig 7. FT-IR Spectra of Chlorpheniramine maleate (pure drug)+MCC+HPMC K4M

Fig 8. FT-IR Spectra of Chlorpheniramine maleate (pure drug)+ MCC+ HPMC K4M+ HPMC 6CPS+PEG 6000


Fig 9. DSC spectrum of CM1 Pure drug

(chlorpheniramine maleate)

Fig 10. DSC spectrum of CM2 (Drug+mcc+Hpmc k4m)

Fig 11. DSC sample of CM 3

(drug+HPMC6CPS+PEG6000)

Fig 12. DSC spectrum of CM4 drug+ MCC+

HPMCK4M+ HPMC6CPS+ PEG6000

Fig 13. Cumulative % drug release for CPM-1 to CPM-9 & Marketed sample (Chlorphen-12)

Observation

Accelerated stability studies of the formulation 9

were done at 40o

C, and at 75%RH for two months. It

was seen that physically there was no change with

respect to appearance hardness, thickness and drug

content. The dissolution profiles of first month and

second moth are similar. When compared to formulation

9 this indicates that the formulation was stable at 40oc

and 75% RH for two months.

DISCUSSION

Chlorpheniramine maleate is an anti cholinergic

anti histaminic, and is a salt of chlorpheniramine. It is

effective against nausea and motion sickness, with its

primary mechanism of action being its ability to reduce

acetylcholine levels in the brain.

From the FT-IR results it is evident that when

Chlorpheniramine maleate as shown in fig. 1 was

compared with MCC, HPMC K4M and HPMC 6CPS,

PEG 6000 and mixture fig.2, 3, 4, 5, 6, 7 and 8 there is no

characteristic change in the peaks. The DSC results

evident that CM1 (pure drug) fig 9 and CM3

(Drug+HPMC 6CPS+PEG 6000) fig.11 and CM4

(Drug+MCC+HPMC K4M+HPMC 6CPS+PEG 6000)

fig 12 exhibits there is no incompatibility. These results

confirm that there is no chemical interaction between

chlorpheniramine maleate and excipients.

Micromeritic properties showed passable

properties for chlorpheniramine maleate. API due to its

amorphous nature when compared with the formulations


CPM-1 to CPM-9 and the results are tabulated in table

no.10 Post-formulation parameters concluded that there

should be certain amount of strength and resistance to

friability for the tablet, so that tablet should not break

during handling which also shows affect on dissolution.

The hardness of chlorpheniramine maleate extended

release tablet ranges from 7.8 to 8.7 kg/cm3. Friability

ranges from 0.157 % to 0.214%. This indicates that

acceptable resistance is shown by chlorpheniramine

maleate ER tablets to withstand handling and the results

are given in table no- 11.

In- vitro dissolution studies showed that, with

increase in the hydrophobic polymer (MCC), the percent

drug release has been retarded, shown in table -12 and fig

no. 13. For all the formulations the dissolution was

conducted for seven hours and among all the

formulations, CPM-9 showed optimum release profile

indicating it to be the best formulation in present

research.

Different model dependent approaches (Zero

order, first order, Higuchi, Korse Meyer-peppas plots)

were performed for all extended release tablets. The

results of these models follow Korse Meyer-peppas

model as” best fit model” follows diffusion mechanism.

This is due to previously proved fact depending on R2

value obtained from model fitting. From the results,

CPM-9 shows more retarding effect and thus found that

T50 % value increases as concentration of MCC increases.

Korse Meyer- Pappas release exponent (n) values of all

chlorpheniramine maleate ER tablets are greater than 1

indicating drug diffusion is rapid due to swelling in the

polymer. The results are tabulated in table no. 13

The stability tests were conducted on CPM-9 and

the formulation was analyzed at initial stage and after one

month and two months at accelerated stage. Accelerated

stability studies of the formulation 9 were done at 40o

C,

and at 75%RH for two months as compared to marketed

tablet. It was seen that physically there was no change

with respect to appearance hardness, thickness and drug

content. The dissolution profiles of first month and

second moth are similar. When compared to formulation

9 this indicates that the formulation was stable at 40oc

and 75% RH for two months.

CONCLUSION The results of the study indicated that polymers

used were suitable for the design of Chlorpheniramine

maleate Extended release tablets providing good release

retarding effect, such that the release of drug content

from core reduces in the gastric pH and increases when

reaches to the intestinal pH which leads to decreased

gastric cavity disorders. Hence, it was concluded that

Chlorpheniramine maleate ER tablets can be formulated

to decrease the gastric irritation and improves patient

compliance with reduction in dosage frequency. It may

also formulate for Future medications with lesser side

effects.

ACKNOWLEDGEMENT Authors are thank full to my Guide (Ramesh Y,

Ratnam Institute of Pharmacy, Nellore), HOD &

Principle for providing the necessary work done in

college.

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