Ctm Formulation

81 Nagamani D. et al. / I nter nter national national Journal J ournal of B i opharma opharmace ceutics. utics. 2015; 6(2): 81-92.

e- ISSN 0976 - 1047 Print ISSN 2229 - 7499

International Journal of Biopharmaceutics

IJB

Journal homepage: www.ijbonline.com

FORMULATION AND EVALUATION OF CHLORPHENIRAMINE MALEATE EXTENDED RELEASE TABLETS BY USING DIRECT COMPRESSION TECHNIQUE 1

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2

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1

Nagamani D* , Ramesh Y , Saravanankumar K , Gnanaprakash K , Gobinath M 1

Department of Pharmaceutics, Ratnam Institute of Pharmacy, Pidathapolur (V & P), Muthukur (M), SPSR Nellore (Dist)524346, Andhra Pradesh., India 2 Department 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 differ ent ratios of polymers and passed through sieve for co mplete 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 3 tablet. The hardness of chlorpheniramine maleate extended release tablet ranges from 7.8 to 8.7 kg/cm . 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 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 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


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 chlorphenirami ne 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 0 (atmosphere). Both the samples were scanned from 30 0 0 300 with the scanning rate of 5 C 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 0 0-900. The angle of repose was calculated by following formula tan θ = h/r -1 θ = tan 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 densitydensity - Bulk density/ Tapped density× 100 Hausner’s ratio Hausner’s ratio is an important 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 – HR<1.25 – indicates indicates good flow property HR>1.25 – HR>1.25 – indicates indicates poor flow property. Post compression parameters The prepared chlorpheniramine maleate extended release tablets were evaluated for following parameters.

W1 Where, W1= Initial weight of tablet and W 2= 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.

I n vitro vitro dissolution studies 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 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 – W W2) × 100

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 0 buffer 6.8 at 37 C 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. 0 The conditions were modified as 25 C/60%RH, 400C/70%RH, 600C/80%RH for every two months i.e., st nd initial, 1 month and 2 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 st nd for initial, 1 month and 2 month for drug content as well as subjected for In for In vitro drug vitro drug release study. RESULTS AND DISCUSSION Drug-excipient compatibility study


their regions of 121.9 0C and 122.5 0C. The DSC spectra of sample code CM4 containing drug+MCC+HPMC K4M+HPM C6CPS+PE G6000, the exothermic peak was 64.7 0C and endothermic 0 peak was 287.5 C. The sample CM3 and CM4 of DSC spectra, the exothermic peak 62.60C and 64.70C, the endothermic 0 0 peak 286.2 C to 287.5 C there is no incompatibility. As shown in figure no11 and 12. And also shown in Table column table no. 9.

Differential scanning calorimetry The DSC spectra of sample (pure drug), the exothermic peak was 122.5 0C and also -10.65mw. The DSC spectra of sample code CM2 containing 0 drug+mcc+HPMCK4M, the exothermic peak was 72.7 C 0 and also 359 C it lies between -4.387mw to -5.950mw. The DSC spectra of sample code CM3 containing drug+HPMC6CPS+PEG6000, the exothermic 0 peak was 121.9 C and -9.29mw and endothermic peak 0 was 286.2 C and -7.50mw.The CM1 and CM3 DSC spectra samples exhibits there is no incompatibility in

Table 1. Formulation table for chlorpheniramine maleate Extended release tablets Formulation in CPM1 CPM2 CPM3 CPM4 CPM5 CPM6 CPM7 CPM8 CPM9 Ratios(mg) 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 26 26 26 26 26 26 26 26 26 stearate Drug-chlorpheniramine maleate (CPM) , MCC- microcrystalline cellulose, NaHPO 2 sodium dihydrogen phosphate dehydrate, HPMC- Hydroxypropyl methyl cellulose, PEG- polyethylene glycol Table 2. Interpretation data for FTIR Spectra of chlorpheniramine maleate -1 IR absorption bands (cm ) Observed peak Characteristic peak

Bond

Functional group

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 0 1 Amines Alkenes

2872,2411,2324,2247,2225,2150

2100-2660 1400-1500 1550-1300

-C=C-

Alkynes

CH2-Scissoring

Amides

1452,1431,1409

Table 3. Interpretation data for FTIR Spectra of micro crystalline cellulose -1 IR absorption bands (cm ) Bond Observed peak Characteristic peak 1330.88 1360-1290 N-O asymmetric stretch 1122.57 1250-1020 C-N stretch 975.98 950-910 O-H bend 848.68 900-675 C-H Table 4. Interpretation data for FTIR Spectra of HPMC K 4M -1 IR absorption bands (cm ) Observed peak Characteristic peak 3462,3446,3367,3348,31903170,31 3500-3100 53,3126 3300-2500 2924,2875,2854,2760,2746 3100-3000 3100-3000

Functional group

Nitro compounds Aliphatic amines Carboxylic acids Aromatics

Bond

Functional group

0-H stretch

H- bonded alcohols, phenols

(M)O-H stretch, (s) C-H stretch

Carboxylic acids, Aromatics


1444,1307

1500-1400

948,839,808,754

1000-650 900-675 910-665 850-550

Table 5. Interpretation data for FTIR Spectra of PEG 6000 -1 IR absorption bands (cm ) Observed peak Characteristic peak 2875,2860, 2900-2695 2800,2697 1242 1200-1250

956,945, 898,842

950-900 975-780

551.6

< 900

(m) C-C stretch( in- ring (s)= C-H bend (s) C-H C-H ”00p” (s,b) N-H wag (m) C-Cl Stretch

Aromatics Alkenes Aromatic 0 0 1 ,2 amines Alkyl halides

Bond

Functional group

C-H stretching

Alkanes

=C-H bend O-H bending (out of plane) -C=H bending C-H bending

Alkyne Phenol

Table 6. Interpretation data for FTIR Spectra of chlorpheniramine maleate + HPMC K4M -1 IR absorption bands (cm ) Bond Observed peak Characteristic peak 3483,3375,3350, 3500-3200 O-H stretch 3315,3290,3275 3100-3000 C-H stretch 3032,3012 3100-3000 =C-H stretch 1357,1332,1319 1360-1290 N-0 symmetric stretch 1000-650 =C-H bend 781,763,754 910-665 N-H wag

Alkenes Alkane

Functional group

H- bonded alcohols, phenols Aromatic alkenes Nitro compounds Alkenes 0 0 1 , 2 amines

Table 7. Interpretation data for FTIR Spectra of chlorpheniramine maleate+ PEG 6000 -1 IR absorption bands (cm ) Bond Functional group Observed peak Characteristic peak 3462,3407,3377, 3500-3250 O-H stretch Phenols, 3367,3352,3300,3282 3400-3250 N-H Stretch 10 amides 3300-2500 O-H stretching Carboxylic acids, 2924,2853,2815,2777,2754,2644 0 0 3400-3250 N-H stretch 1 , 2 amides, amines 1760-1665 C=O stretch Carbonyls, α,β unsaturated 1670.35 1680-1640 -C=C- stretch ketones 1273,1107,1095 1330-1100 C-N stretch Aromatic amines Table 8. Interpretation data for FTIR Spectra of chlorpheniramine maleate+MCC+HPMC K4M -1 IR absorption bands (cm ) Bond Functional group Observed peak Characteristic peak 3367,3342,3304 3400-3250 N-H stretch 10 amines, amides, alkenes 3275,3228 3300-3270 C-H stretch 0 1632.6 1650-1580 N-H bend 1 amines 1400.32 1550-1475 N-O asymmetric stretch Nitro compounds 1357,1332, 1261, 1370-1350 C-H rock Alkanes 1335-1250 C-N stretch Aromatic amines Table 9. Interpretation data for FTIR Spectra of chlorpheniramine maleate+MCC+HPMC K4M+HPMC 6CPS+PEG 6000 IR absorption bands (cm ) Bond Functional group Observed peak Characteristic peak


3628,3599,3396, 3383,3367,3298 3238

3650-3250 3400-3200

O-H stretch N-H stretch

Carboxylic acids, 1 , 2 amides

1585,4

1650-1580 1600-1585

N-H bend C-C stretch( in-ring)

1 Amines, Aromatics

1413,1400

1550-1475 1500-1400

N-O asymmetric stretch C-C stretch(in-ring)

999.1,950.1,873

1000-650

=C-H bend

0

0

0

Nitro compounds Aromatics Alkenes

Table 10. Data of DSC SPETRAS of SAMPLES F.code CM1 CM2 CM3 CM4

Exothermic 122.50C -10.65mw 72.70C -4.387mw 121.90C -9.29mw 64.70C -3.786mw

Endothermic --286.20C -7.50mw 287.50C -7.85mw

Pre compression (micro meritic) parameters for chlorpheniramine maleate extended release tablets Table 11. Micro meritic parameters Derived properties Flow properties Bulk density Tapped density Angle of repose Carr’s index Hausner’s ratio F.code (mean±SD) (mean±SD) (mean±SD) (mean±SD) (mean± SD) 3 3 (g/cm ) (g/cm ) (Degree) (%) (%) 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 Thickness Hardness Friability Mean SD Mean SD Mean SD F. Code 3 (mm) (kg/cm ) (%) CPM-1 3.22 8.3 0.159 CPM-2 3.35 8.7 0.167 CPM-3 3.48 7.8 0.214 CPM-4 3.52 8.5 0.157 CPM-5 3.48 8.3 0.115 CPM-6 3.37 8.5 0.156 CPM-7 3.35 7.9 0.167 CPM-8 3.52 8.3 0.146 CPM-9 3.48 7.8 0.157

Weight variation Mean SD (mg) 497±0.4 498±0.5 499±0.2 497±0.4 496±0.5 493±0.2 497±0.4 496±0.5 498±0.4

In-vitro Drug release studies of chlorpheniramine maleate extended release tablets: Table 13. In- vitro drug release profile of chlorpheniramine maleate extended release tablets Cumulative % drug release Time (hrs) CPM-1 CPM-2 CPM-3 CPM-4 1 10.2 10.6 11.1 11.3 2 16.5 17.4 23.4 25.3

Drug content Mean SD

98.3±0.5 98.5±0.2 99.2±0.5 96.4±0.6 97.3±0.7 99.2±0.6 99.4±0.5 98.7±0.6 98.3±0.7

CPM-5 11.7 29.1


3 4 5 6 7 8 9

29.3 38.1 48.6 57.6 75.6 84.9 97.2

30.2 39.7 50.9 66.6 77.4 86.4 98.6

31.1 43.3 55.4 68.4 79.2 86.7 97.5

35.4 47.5 57.6 70.1 79.9 87.1 98.8

39.7 50.7 63.1 70.5 80.8 88.2 98.6

Table 14. In-vitro drug release profile of chlorpheniramine maleate ER tablets of formulation CPM-6 to CPM-9 & marketed sample Cumulative % drug release Time (hrs) 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

F.code CPM 1 CPM 2 CPM 3 CPM 4 CPM 5 CPM 6 CPM 7 CPM 8 CPM 9

Zero order

R 2 0.993 0.996 0.997 0.997 0.989 0.973 0.964 0.958 0.934

M -32.30 -26.26 2.783 22.09 48.96 79.28 95.84 108.78 136.1

First order

R 2 0.781 0.695 0.822 0.756 0.864 0.77 0.792 0.792 0.795

M -0.359 0.4001 0.375 0.431 0.355 0.413 0.399 0.411 0.408

Higuchi

R 2 0.881 0.978 0.987 0.995 0.998 0.993 0.988 0.978 0.972

M -62.31 -37.89 -33.03 3106.0 -2768.6 -2350.2 -2105.3 -3708.9 -1640.8

Korse Meyer Pappas R 2 M 0.988 0.972 0.406 0.723 0.906 1.287 0.990 0.938 0.985 1.096 0.971 1.113 0.95 1.104 0.945 1.089 0.928 1.105

Hixson

R 2 0.979 0.972 0.959 0.943 0.915 0.880 0.861 0.856 0.818

M 0.611 0.628 0.636 0.641 0.646 0.641 0.634 0.632 0.622

STABILIY STUDIES Table 16. Physical evaluation of tablet blend and tablets of optimization of stability formulations cumulative % drug release ( Best cumulative % drug release ( I nnova nnovato torr Formulation code CPM 9) B r and N ame ame: Chlorp Chlor phen-12 hen-12 ) Two One Two Time (Hr) Initial One month Initial months month 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 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 Parameters Color

Initial Cream or White

One month Cream or White

Two months Cream or White


Surface Thickness Hardness Assay

Smooth 3.3-3.4 4 99.3

Smooth 3.3-3.4 4 100.6

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

Fig 2. FT-IR Spectra of Micro crystalline cellulose

Smooth 3.3-3.4 4 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 40 o 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 40 oc 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 t o 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 3 release tablet ranges from 7.8 to 8.7 kg/cm . 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. 2 This is due to previously proved fact depending on R 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 40 o 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 o 9 this indicates that the formulation was stable at 40 c 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 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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Ctm Formulation

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