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Formulation and Evaluation of Cephalexin Extended Release Matrix Tablets Using 32 Factorial Design
Pharmaceutics
Formulation and Evaluation of Cephalexin Extended Release Matrix Tablets Using 32 Factorial Design Jishnu V, Prabhakaran R1, Gilhotra RM Department of Pharmaceutics, School of Pharmacy, Suresh Gyan Vihar University, Jaipur, 1 Sance Laboratories Pvt. Ltd., Kottayam, Kerala, India Address for correspondence: Dr. Ritu M Gilhotra; E-mail: [email protected]
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INTRODUCTION
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Journal of Young Pharmacists Vol 3 / No 4
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Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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7DEOH 3UHFRPSUHVVLRQSDUDPHWHUVRI¿QDOEDWFKHV F1–F9 Code
F1 F2 F3 F F F F F F9
Angle of repose (T)* 1ƍ 1ƍ 2 333ƍ 3ƍ 3231ƍ 33ƍ 1 31ƍ 3 32ƍ 2 33ƍ
Bulk density (g/cm3) 1 2 3 1 32 22 12
Tapped density (g/cm3) 1 2 2 2 31 1
Carr’s index (%)
Hausner’s ratio
1 1 122 11 1 1 2 1 1 2 11 1 1 23 119 9
1 11 11 121 12 33 12 1 122 2 12 119 9
*7KH YDOXHV DUH H[SUHVVHG DV 0HDQ 6' n=3
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MATERIALS AND METHODS
Materials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ethods Preparation and evaluation of cephalexin monohydrate granules[7] $FFXUDWHO\ ZHLJKHG TXDQWLWLHV RI GUXJ DQG H[FLSLHQWV ZHUH SDVVHG WKURXJK VLHYH QR DQG UHVSHFWLYHO\ 'UXJ DQG H[FLSLHQWV H[FOXGLQJ OXEULFDQW ZHUH DGGHG LQ JHRPHWULF SURSRUWLRQV DQG PL[HG WKRURXJKO\ IRU PLQ 7KH EOHQG ZDV PL[HG ÀQDOO\ ZLWK OXEULFDQW WR JHW WKH JUDQXOHV RI FHSKDOH[LQ PRQRK\GUDWH 7KH ÁRZ SURSHUWLHV RI JUDQXOHV ZHUH FKDUDFWHUL]HG LQ WHUPV RI DQJOH RI UHSRVH &DUU·V LQGH[ DQG +DXVQHU·V UDWLR 7KH EXON GHQVLW\ DQG WDSSHG GHQVLW\ ZHUH GHWHUPLQHG XVLQJ 863 EXON GHQVLW\ DSSDUDWXV 9HHJR ,QGXVWULHV 0XPEDL ,QGLD 7KH GDWD VXPPDUL]HG LQ 7DEOH Formulation of cephalexin matrix tablets using direct compression method[8] 7KH SUHSDUHG JUDQXOHV RI FHSKDOH[LQ PRQRK\GUDWH ZHUH FRPSUHVVHG LQ ï PP SXQFKHV RI VWDWLRQ URWDU\ WDEOHW FRPSUHVVLRQ PDFKLQH &0%' &DGPDFK $KPDGDEDG ,QGLD 7KH IRUPXODH IRU EDWFKHV )²) DUH VKRZQ LQ 7DEOHV DQG 260
Ingredients Cephalexin monohydrate Microcrystalline cellulose +3MC .1M +3MC .1cps Colloidal silicon dioxide Magnesium stearate Average tablet weight
F1 12 221
Quantity used (mg/tab) F2 F3 F4 12 12 12 3 33 2 11
F5 12 2 2
7DEOH &RPSRVLWLRQRIRSWLPL]DWLRQEDWFKHVF–F9 Ingredients Cephalexin monohydrate Microcrystalline cellulose +3MC .1M +3MC .1cps Colloidal silicon dioxide Magnesium stearate Average tablet weight
F6 12 192 11
Quantity used (mg/tab) F7 F8 12 12 3 9 3 3 2
F9 12 3 3 11
Evaluation of tablet properties[8,9] 7KH SUHSDUHG FHSKDOH[LQ PDWUL[ WDEOHWV ZHUH HYDOXDWHG IRU WKLFNQHVV KDUGQHVV IULDELOLW\ XQLIRUPLW\ RI ZHLJKW DQG GUXJ FRQWHQW 7KH WKLFNQHVVHV RI WDEOHWV ZHUH PHDVXUHG XVLQJ YHUQLHU FDOLSHU $HURVSDFH &KLQD +DUGQHVV RI WDEOHWV ZDV WHVWHG XVLQJ D YDOLGDWHG PRGLÀHG GLDO W\SH KDUGQHVV WHVWHU 6KLYDQL 6FLHQWLÀF ,QGXVWULHV 0XPEDL ,QGLD )ULDELOLW\ RI WDEOHWV ZDV GHWHUPLQHG E\ XVLQJ 5RFKH )ULDELODWRU (OHFWURODEV %DQJORUH ,QGLD 7KH GUXJ FRQWHQW RI HDFK EDWFK ZDV GHWHUPLQHG DV SHU 863 DVVD\ RI FHSKDOH[LQ XVLQJ KLJK SHUIRUPDQFH OLTXLG FKURPDWRJUDSK\ +3/& 6&/$93 6KLPDG]X &RUSRUDWLRQ -DSDQ >@ 7KH UHVXOWV DUH VKRZQ LQ 7DEOH In vitro drug release study 7KH GUXJ UHOHDVH VWXGLHV RI FHSKDOH[LQ PDWUL[ WDEOHWV ZHUH SHUIRUPHG XVLQJ GLVVROXWLRQ WHVWLQJ DSSDUDWXV 863 W\SH , %DVNHW W\SH (OHFWURODEV %DQJORUH ,QGLD 7KH GLVVROXWLRQ Journal of Young Pharmacists Vol 3 / No 4
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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F1 F2 F3 F F F F F F9
Weight variation (%)* 132 13 23 21 213 1 2 29 1 313 231 22 112 319 2 3 22 23
Thickness (mm)*
Hardness (kg/cm2)*
2 3 3 2
12 111 129 22 1123 12 11 1 12 22 1222 23 11 1 11 222 1 23
Drug content (%) 919 9 912 9 923 91 99 9 93
Friability (%)** 3 3 1 3 2 3 2 1 3 2 2
9alues are expressed as mean 6' n=2
9alues are expressed as mean 6' n=3
Figure 1: Cumulative percentage drug release of F1–F5 Journal of Young Pharmacists Vol 3 / No 4
ORZ PHdLXP Dnd KLJK UHVSHFWLYHO\ DV UHSUHVHnWHd Ln 7DEOH 7KH VWDWLVWLFDO RSWLPL]DWLRn SURFHdXUH ZDV SHUIRUPHd ZLWK WKH KHOS RI RSWLPL]DWLRn VRIWZDUHV OLNH 'HVLJn ([SHUW 6WDW(DVH ,nF 0LnnHDSROLV 01 86A Table : 'issolXtion pro¿les of optimization batcKes F1–F9 Formulation code F1 F2 F3 F F F F F F9
Cumulative percentage drug release (%)* 1st h 2nd h 4th h 6th h 3931 3 99 1 99 93 11 9 2 999 12 2 99 9 129 31 112 9 1 2 1 93 21 3 1 13 33 3 9 12 2 3 9 9 9 1 33 9 22 321 9 93 39 12 3 19 21 11 912 92 9 39 11 9 9 313 13 1 1 93 93 9
9alues are expressed as mean 6' n=
Table : Factors anG responses eYalXateG in 2 factorial GesiJn Formulation code
F1 F2 F3 F F F F F F9
Factors in coded form HPMC HPMC K15M 15cps (X1) (X2) 1 1 1 1 í1 1 1 í1 í1 í1 í1 í1
Responses (%) Drug release at 1st h (Y1) 21 33 31 3931 313 9 39
Drug release at 2nd h (Y2) 1 22 9 999 3 3 9
Drug release at 4th h (Y3) 33 321 2 1 1 2 21 9 39
Table : &orrelation of actXal anG coGeG factors Factor level
Low Medium High
Coded form í1 +1
Actual value (mg) HPMC HPMC K15M K15M 3 2 11
Actual value (%) HPMC HPMC K15M 15cps 12 1 1 1
Figure 2: Cumulative percentage drug release of F6–F9 261
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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DF 1 1 1 1 1 3
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F ratio 9 21 13
P value 1 1 19 19 291
F ratio 2 293 12 1 119
P value 339 32 23
6igni¿cant values ³'F´ stands Ior degree oI Ireedom
Table 9: $nal\sis of Yariance for 2nG K Source A .1M B 1C36 AA AB BB Total error Total corr
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DF 1 1 1 1 1 3
Mean square 991 11329 122
6igni¿cant values ³'F´ stands Ior degree oI Ireedom
263
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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DF 1 1 1 1 1 3
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F ratio 122 29 119 21
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Table 11: .inetics moGelinJ sXmmar\ Code Zero order R2 K0 F1 F2 F3 F F F F F F9
9 9 99 9 99 99 99 993 993
99 11 2131 1 92 29 1 12 212
Kinetic model First order Korsemeyer R2 K1 R2 n 92 9 9 9 92 99
9 39 3 3 13 12 3 9
9 93 99 9 99 9 99 9 9
3 2 3 3 3
Higuchi R2 KH 9 9 993 9 9 9 99 9 99
3 31 3 3 323 29 3 332 29
R2 = regression coeI¿cient . = ]eroorder release rate constant .1 = ¿rstorder release rate constant n=diIIusional exponent .H = Higuchi rate constant
Figure 3: 3D plot for percentage drug release at the 1st h 264
Figure 4: 3D plot for percentage drug release at the 2nd h Journal of Young Pharmacists Vol 3 / No 4
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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Figure 5: 3D plot for percentage drug release at 4th h
Future prospects of the study Table 12: 6imilarit\ factor of formXlations F1–F9 Code
Similarity factor (f2)
F1 F2 F3 F F F F F F9
113 22 9 3 29 919
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Assay (%)
Appearance
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2II white color 2II white color
CONCLUSIONS
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Formulation and Evaluation of Cephalexin Extended Release Matrix Tablets Using 32 Factorial Design Jishnu V, Prabhakaran R1, Gilhotra RM Department of Pharmaceutics, School of Pharmacy, Suresh Gyan Vihar University, Jaipur, 1 Sance Laboratories Pvt. Ltd., Kottayam, Kerala, India Address for correspondence: Dr. Ritu M Gilhotra; E-mail: [email protected]
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INTRODUCTION
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Journal of Young Pharmacists Vol 3 / No 4
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Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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7DEOH 3UHFRPSUHVVLRQSDUDPHWHUVRI¿QDOEDWFKHV F1–F9 Code
F1 F2 F3 F F F F F F9
Angle of repose (T)* 1ƍ 1ƍ 2 333ƍ 3ƍ 3231ƍ 33ƍ 1 31ƍ 3 32ƍ 2 33ƍ
Bulk density (g/cm3) 1 2 3 1 32 22 12
Tapped density (g/cm3) 1 2 2 2 31 1
Carr’s index (%)
Hausner’s ratio
1 1 122 11 1 1 2 1 1 2 11 1 1 23 119 9
1 11 11 121 12 33 12 1 122 2 12 119 9
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MATERIALS AND METHODS
Materials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ethods Preparation and evaluation of cephalexin monohydrate granules[7] $FFXUDWHO\ ZHLJKHG TXDQWLWLHV RI GUXJ DQG H[FLSLHQWV ZHUH SDVVHG WKURXJK VLHYH QR DQG UHVSHFWLYHO\ 'UXJ DQG H[FLSLHQWV H[FOXGLQJ OXEULFDQW ZHUH DGGHG LQ JHRPHWULF SURSRUWLRQV DQG PL[HG WKRURXJKO\ IRU PLQ 7KH EOHQG ZDV PL[HG ÀQDOO\ ZLWK OXEULFDQW WR JHW WKH JUDQXOHV RI FHSKDOH[LQ PRQRK\GUDWH 7KH ÁRZ SURSHUWLHV RI JUDQXOHV ZHUH FKDUDFWHUL]HG LQ WHUPV RI DQJOH RI UHSRVH &DUU·V LQGH[ DQG +DXVQHU·V UDWLR 7KH EXON GHQVLW\ DQG WDSSHG GHQVLW\ ZHUH GHWHUPLQHG XVLQJ 863 EXON GHQVLW\ DSSDUDWXV 9HHJR ,QGXVWULHV 0XPEDL ,QGLD 7KH GDWD VXPPDUL]HG LQ 7DEOH Formulation of cephalexin matrix tablets using direct compression method[8] 7KH SUHSDUHG JUDQXOHV RI FHSKDOH[LQ PRQRK\GUDWH ZHUH FRPSUHVVHG LQ ï PP SXQFKHV RI VWDWLRQ URWDU\ WDEOHW FRPSUHVVLRQ PDFKLQH &0%' &DGPDFK $KPDGDEDG ,QGLD 7KH IRUPXODH IRU EDWFKHV )²) DUH VKRZQ LQ 7DEOHV DQG 260
Ingredients Cephalexin monohydrate Microcrystalline cellulose +3MC .1M +3MC .1cps Colloidal silicon dioxide Magnesium stearate Average tablet weight
F1 12 221
Quantity used (mg/tab) F2 F3 F4 12 12 12 3 33 2 11
F5 12 2 2
7DEOH &RPSRVLWLRQRIRSWLPL]DWLRQEDWFKHVF–F9 Ingredients Cephalexin monohydrate Microcrystalline cellulose +3MC .1M +3MC .1cps Colloidal silicon dioxide Magnesium stearate Average tablet weight
F6 12 192 11
Quantity used (mg/tab) F7 F8 12 12 3 9 3 3 2
F9 12 3 3 11
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F1 F2 F3 F F F F F F9
Weight variation (%)* 132 13 23 21 213 1 2 29 1 313 231 22 112 319 2 3 22 23
Thickness (mm)*
Hardness (kg/cm2)*
2 3 3 2
12 111 129 22 1123 12 11 1 12 22 1222 23 11 1 11 222 1 23
Drug content (%) 919 9 912 9 923 91 99 9 93
Friability (%)** 3 3 1 3 2 3 2 1 3 2 2
9alues are expressed as mean 6' n=2
9alues are expressed as mean 6' n=3
Figure 1: Cumulative percentage drug release of F1–F5 Journal of Young Pharmacists Vol 3 / No 4
ORZ PHdLXP Dnd KLJK UHVSHFWLYHO\ DV UHSUHVHnWHd Ln 7DEOH 7KH VWDWLVWLFDO RSWLPL]DWLRn SURFHdXUH ZDV SHUIRUPHd ZLWK WKH KHOS RI RSWLPL]DWLRn VRIWZDUHV OLNH 'HVLJn ([SHUW 6WDW(DVH ,nF 0LnnHDSROLV 01 86A Table : 'issolXtion pro¿les of optimization batcKes F1–F9 Formulation code F1 F2 F3 F F F F F F9
Cumulative percentage drug release (%)* 1st h 2nd h 4th h 6th h 3931 3 99 1 99 93 11 9 2 999 12 2 99 9 129 31 112 9 1 2 1 93 21 3 1 13 33 3 9 12 2 3 9 9 9 1 33 9 22 321 9 93 39 12 3 19 21 11 912 92 9 39 11 9 9 313 13 1 1 93 93 9
9alues are expressed as mean 6' n=
Table : Factors anG responses eYalXateG in 2 factorial GesiJn Formulation code
F1 F2 F3 F F F F F F9
Factors in coded form HPMC HPMC K15M 15cps (X1) (X2) 1 1 1 1 í1 1 1 í1 í1 í1 í1 í1
Responses (%) Drug release at 1st h (Y1) 21 33 31 3931 313 9 39
Drug release at 2nd h (Y2) 1 22 9 999 3 3 9
Drug release at 4th h (Y3) 33 321 2 1 1 2 21 9 39
Table : &orrelation of actXal anG coGeG factors Factor level
Low Medium High
Coded form í1 +1
Actual value (mg) HPMC HPMC K15M K15M 3 2 11
Actual value (%) HPMC HPMC K15M 15cps 12 1 1 1
Figure 2: Cumulative percentage drug release of F6–F9 261
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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DF 1 1 1 1 1 3
Mean square 2291 293 3922 12323 1311 912
F ratio 9 21 13
P value 1 1 19 19 291
F ratio 2 293 12 1 119
P value 339 32 23
6igni¿cant values ³'F´ stands Ior degree oI Ireedom
Table 9: $nal\sis of Yariance for 2nG K Source A .1M B 1C36 AA AB BB Total error Total corr
Sum of squares 991 11329 12 2
DF 1 1 1 1 1 3
Mean square 991 11329 122
6igni¿cant values ³'F´ stands Ior degree oI Ireedom
263
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
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DF 1 1 1 1 1 3
Mean square 29121 223 9 3 23
F ratio 122 29 119 21
P value 1 1 3 1 2
6igni¿cant values ³'F´ stands Ior degree oI Ireedom
Table 11: .inetics moGelinJ sXmmar\ Code Zero order R2 K0 F1 F2 F3 F F F F F F9
9 9 99 9 99 99 99 993 993
99 11 2131 1 92 29 1 12 212
Kinetic model First order Korsemeyer R2 K1 R2 n 92 9 9 9 92 99
9 39 3 3 13 12 3 9
9 93 99 9 99 9 99 9 9
3 2 3 3 3
Higuchi R2 KH 9 9 993 9 9 9 99 9 99
3 31 3 3 323 29 3 332 29
R2 = regression coeI¿cient . = ]eroorder release rate constant .1 = ¿rstorder release rate constant n=diIIusional exponent .H = Higuchi rate constant
Figure 3: 3D plot for percentage drug release at the 1st h 264
Figure 4: 3D plot for percentage drug release at the 2nd h Journal of Young Pharmacists Vol 3 / No 4
Jishnu, et al.: Formulation and evaluation of cephalexin extended release tablet
Figure 6: %QORCTCVKXG FKUUQNWVKQP RTQſNGU QH OCTMGVGF RTQFWEV ( CPFVJGQTGVKECNTGNGCUGRTQſNG
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Figure 5: 3D plot for percentage drug release at 4th h
Future prospects of the study Table 12: 6imilarit\ factor of formXlations F1–F9 Code
Similarity factor (f2)
F1 F2 F3 F F F F F F9
113 22 9 3 29 919
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Table 1: $ccelerateG stabilit\ stXGies report of cepKale[in (5 Period Intial Final
Dissolution (%) 1st h 2nd h 4th h 6th h 31 9 2 93 32 3 19 91
Assay (%)
Appearance
912 9
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