|
|
|
Sample Product Manufacturer Country Strengtha (mg) Lot number Reference Klacid® Abbott Uruguay 250 16-839-ZE Reference Klacid® Abbott Brazil 500 35-234QP Latin American region 1 Clarimax Gautier Uruguay 250 120 04 6 2 Macrolien Galien Uruguay 250 L6004 3 Clarimicin Laboratorios Lopez El Salvador 250 04 4 Claritromicina MK Bonima S.A. (McKesson Corp., USA) El Salvador 500 98050420 5 Claribac Lancasco Guatemala 500 L6140 6 Dicupal Pharma Investi Peru 250 910016
REG No. 184507 Dicupal Pharma Investi Peru 500 910016
REG No. 184518 Infex Pharmafina Chile 250 F97387 9 Infex Pharmafina Chile 500 F97389 10 Mus Instituto Bioquimico Beta Chile 250 0332797 11 Mus Instituto Bioquimico Beta Chile 500 0332897 12 Pre-Clar Laboratorio Chile Chile 250 98016904 13 Pre-Clar Laboratorio Chile Chile 500 98016905 14 Claritrol Legrand Columbia 250 7-LC2T-01 15 Claritrol Legrand Columbia 500 7-LC5T-02 16 Claritromicina Laboratorio Bergamo Brazil 500 B0548 17 Clamicin Medley S.A. Brazil 500 L9712128 18 Claritrobac Stein Laboratorios Costa Rica 500 140C8V0300 Asian region 19 Crixan Ranbaxy India 250 D00197 20 Crixan Ranbaxy India 250 D00397 21 Synclar Cipla India 250 A70341 22 Clarithro-250 Alembic Chemical Works India 250 89752 23 Clamycin Lupin Laboratories India 250 8001 24 Klarid Kalbe Farma Indonesia 250 831001 25 Clacine Dankos Indonesia 250 01301 26 Comtro Combiphar Indonesia 250 U 035024 27 Bicrolid Sanbe Indonesia 250 0397363 28 Clambiotic P.T. Bintang Toedjoe Indonesia 250 570185 29 Clarion Ferozsons Laboratories Pakistan 250 6J168 30 Klax Toprak Ilac Turkey 250 7070363 31 Klax Toprak Ilac Turkey 500 7070387 32 Macrol Sanovel Turkey 250 099702SK 33 Macrol Sanovel Turkey 500 099706SK 34 Klarolid Ilsan-Iltas Turkey 500 711003 35 Klarolid Ilsan-Iltas Turkey 500 804011 36 Klax Toprak Turkey 500 8020170 37 Macrol Sanovel Turkey 500 29SK 38 Claricide Bilim Ilac San ve Tic Turkey 500 001 39 Klaromin Eczacibasi Turkey 500 809447 40 Limaixian Shanxi Province Sian China 250 9708198 aAll of the formulations are tablets, except number 2, which is a capsule.
Impurityb 1 2 3 4 5 6 7 8 9 10 Mean SD Declad 0.04 0.01 0.04 0.04 0.02 0.05 0.04 0.04 0.02 0.04 0.013 EM=NOH (E) 0.02 0.01 0.01 0.02 0.01 0.02 0.02 0.02 0.005 =NOH (Z) 0.02 0.01 0.02 0.03 0.03 0.03 0.03 0.02 0.03 0.02 0.007 =NOH,NH(E) 0.02 0.02 0.000 =NOH (E) 0.12 0.17 0.08 0.12 0.12 0.12 0.10 0.27 0.12 0.12 0.13 0.053 -NH 0.16 0.17 0.16 0.13 0.14 0.17 0.06 0.13 0.12 0.19 0.14 0.037 6,11-Di-O-Me 0.17 0.20 0.15 0.18 0.16 0.22 0.14 0.18 0.19 0.23 0.18 0.029 Di-O-Me 0.21 0.23 0.19 0.20 0.33 0.22 0.29 0.21 0.30 0.24 0.23 0.046 6,4-Di- O-Me 0.08 0.10 0.08 0.08 0.07 0.08 0.06 0.09 0.08 0.10 0.08 0.012 =NOMe (Z) 0.04 0.05 0.03 0.03 0.04 0.03 0.04 0.04 0.04 0.04 0.007 =NOMe(E) 0.37 0.39 0.29 0.32 0.37 0.38 0.34 0.32 0.36 0.36 0.35 0.032 N-formyl 0.04 0.01 0.03 0.04 0.05 0.02 0.02 0.04 0.06 0.04 0.014 Total 1.19 1.31 0.99 1.09 1.26 1.28 1.04 1.26 1.25 1.34 1.20 0.120 aA representative lot was assayed a total of ten times by two different analysts using different HPLC systems.
bSee text ('Materials and Methods', under 'Impurity Content') for an explanation of abbreviations, which follow the same system as that in Morgan et al.[7]HPLC = high pressure liquid chromatography; SD = standard deviation.
Sample Product Country External appearancea Internal appearancea Reference Klacid® Uruguay Yellow (3945U), oval, coated pale yellow Reference Klacid® Brazil Yellow (100C), oval, coated white, granular Latin American Region 1 Clarimax Uruguay Pale yellow (100 U), oval, mottled White 2 Macrolien Uruguay Red (187C) and gray (435C) capsule White powder 3 Clarimicin El Salvador Off-white, oval, mottled White 4 Claritromicina MK El Salvador Yellow (127C), oval, coated White, granular 5 Claribac Guatemala White, oval White 6 Dicupal Peru Off-white, oval White 7 Dicupal Peru Pale flesh (489C), oval White 8 Infex Chile Pale yellow (1205C), oval Yellow (100U), granular 9 Infex Chile Pale yellow (1205C), oval Yellow (100U), granular 10 Mus Chile Flesh (1555C), ovalb Pale flesh (1555U), granular 11 Mus Chile White, oblong White, coarse texture 12 Pre-Clar Chile Green (359C), oblong, coated White, granular 13 Pre-Clar Chile Green (360C), oblong, coated White, granular 14 Claritrol Columbia Blue (304U), circular/oval, coated Blue (2975C), granular 15 Claritrol Columbia White/off-white, oval, coated White/off-white, granular 16 Claritromicina Brazil Blue (643C), oval, coated White/off-white, granular 17 Clamicin Brazil White, oblong/oval, coated White, granular 18 Claritrobac Costa Rica Yellow (393C), oval, coated White, granular Asian region 19 Crixan India Yellow (600U), oval White, coarse granular 20 Crixan India Pale yellow (615U), oval White, granular 21 Synclar India White, oval, coated White, granular 22 Clarithro-250 India Purple/blue (2708C), circular, coated White, granular 23 Clamycin India Yellow (106C), oval, coated White, granular 24 Klarid Indonesia White, oval/oblong White, coarse granular 25 Clacine Indonesia Yellow (100C), oval White, granular 26 Comtro Indonesia Yellow (101C), oval/oblong White, granular 27 Bicrolid Indonesia Pale yellow (607U), oval, casing, chips White, granular 28 Clambiotic Indonesia Yellow (101C), oval, soft White, granular 29 Clarion Pakistan Pale orange (1485C), oval White 30 Klax Turkey Pale yellow (601U), oval, one cracked Pale yellow (600U), granular 31 Klax Turkey Pale yellow (601U), ovalb Pale yellow (600U), granular 32 Macrol Turkey Yellow (102U), oval, coated White, granular 33 Macrol Turkey Pale green (587U), oval, coated White/off-white, granular 34 Klarolid Turkey Yellow (601U), oval, coated White, granular 35 Klarolid Turkey Yellow (393C), oval, coated White, granular 36 Klax Turkey Yellow (600U), oval, coated, discoloured Yellow (600U), granular 37 Macrol Turkey Yellow (600C), oval, coated White, granular 38 Claricide Turkey Yellow (603U), oval Yellow (600U), granular 39 Klaromin Turkey Yellow (101C), oval, coated White, granular 40 Limaixian China Yellow (102C), oval, coated White, granular aPantone colour match in parentheses, when available.
bSome tablets found to have darker specks of colour.
Sample Product Country Mean clarithromycin
content (mg/dose)Percentage of label claim Reference Klacid® (250mg) Uruguay 249 99.6 Reference Klacid® (500mg) Brazil 488 97.6 Latin American region 3 Clarimicin El Salvador 214 85.6 1 Clarimax Uruguay 230 92.0 16 Claritromicina Brazil 466 93.2 6 Dicupal Peru 235 94.0 5 Claribac Guatemala 472 94.4 7 Dicupal Peru 477 95.4 4 Claritromicina MK El Salvador 479 95.8 11 Mus Chile 481 96.2 15 Claritrol Columbia 483 96.6 9 Infex Chile 484 96.8 10 Mus Chile 243 97.2 14 Claritrol Columbia 244 97.6 8 Infex Chile 245 98.0 2 Macrolien Uruguay 245 98.0 18 Claritrobac Costa Rica 495 99.0 17 Clamicin Brazil 502 100.4 12 Pre-Clar Chile 257 102.8 13 Pre-Clar Chile 536 107.2 Asian region 29 Clarion Pakistan 221 88.4 25 Clacine Indonesia 226 90.4 26 Comtro Indonesia 239 95.6 24 Klarid Indonesia 239 95.6 28 Clambiotic Indonesia 239 95.6 32 Macrol Turkey 241 96.4 33 Macrol Turkey 483 96.6 30 Klax Turkey 242 96.8 40 Limaixian China 242 96.8 22 Clarithro-250 India 243 97.2 20 Crixan India 245 98.0 21 Synclar India 246 98.4 19 Crixan India 246 98.4 37 Macrol Turkey 493 98.6 34 Klarolid Turkey 494 98.8 31 Klax Turkey 495 99.0 27 Bicrolid Indonesia 248 99.2 23 Clamycin India 249 99.6 38 Claricide Turkey 499 99.8 39 Klaromin Turkey 502 100.4 36 Klax Turkey 503 100.6 35 Klarolid Turkey 506 101.2
Sample Product Country Mean % dissolved
at 30 min.Range (%) Reference Klacid® (250mg) Uruguay 95 93-98 Reference Klacid® (500mg) Brazil 94 90-98 Latin American region 9 Infex Chile 80 74-84 3 Clarimicin El Salvador 82 75-88 5 Claribac Guatemala 84 68-91 12 Pre-Clar Chile 86 75-94 4 Claritromicina MK El Salvador 87 83-89 18 Claritrobac Costa Rica 88 81-94 7 Dicupal Peru 89 88-91 11 Mus Chile 89 88-90 2 Macrolien Uruguay 91 83-96 15 Claritrol Columbia 92 89-96 1 Clarimax Uruguay 92 90-95 6 Dicupal Peru 92 90-95 8 Infex Chile 93 90-96 10 Mus Chile 94 92-97 16 Claritromicina Brazil 95 93-96 17 Clamicin Brazil 97 94-100 14 Claritrol Columbia 98 95-100 13 Pre-Clar Chile 99 98-100 Asian region 29 Clarion Pakistan 46 15-67 28 Clambiotic Indonesia 82 75-89 25 Clacine Indonesia 86 83-88 37 Macrol Turkey 86 85-87 24 Klarid Indonesia 87 83-89 36 Klax Turkey 88 87-90 27 Bicrolid Indonesia 89 82-92 32 Macrol Turkey 89 85-91 26 Comtro Indonesia 89 87-91 40 Limaixian China 90 87-92 33 Macrol Turkey 90 88-93 39 Klaromin Turkey 91 81-94 22 Clarithro-250 India 91 87-94 35 Klarolid Turkey 91 88-93 20 Crixan India 92 90-97 31 Klax Turkey 94 90-97 34 Klarolid Turkey 94 90-97 21 Synclar India 94 93-95 23 Clamycin India 96 92-98 19 Crixan India 97 94-99 30 Klax Turkey 97 95-98 38 Claricide Turkey 97 96-97
Sample Product Country 6,11 di-O-methyl
erythromycin A (%)Total impurities (%) Reference Klacid® (250mg) Uruguay 0.27 1.96 Reference Klacid® (500mg) Brazil 0.36 2.33 Latin American region 16 Claritromicina Brazil 3.53 30.56 1 Clarimax Uruguay 1.84 20.24 3 Clarimicin El Salvador 3.52 7.00 14 Claritrol Columbia 1.40 5.21 9 Infex Chile 1.07 4.86 8 Infex Chile 1.12 3.71 12 Pre-Clar Chile 0.96 3.60 7 Dicupal Peru 1.75 3.54 4 Claritromicina MK El Salvador 1.25 3.53 5 Claribac Guatemala 0.67 3.47 17 Clamicin Brazil 1.20 3.41 6 Dicupal Peru 1.73 3.38 13 Pre-Clar Chile 0.95 3.32 15 Claritrol Columbia 1.23 3.18 11 Mus Chile 1.29 2.73 2 Macrolien Uruguay 0.68 2.72 18 Claritrobac Costa Rica 0.78 2.64 10 Mus Chile 1.24 2.61 Asian region 21 Synclar India 0.42 14.30 29 Clarion Pakistan 1.64 10.54 37 Macrol Turkey 0.51 4.79 25 Clacine Indonesia 1.76 4.77 40 Limaixian China 1.46 4.12 28 Clambiotic Indonesia 1.38 3.78 23 Clamycin India 0.82 3.68 24 Klarid Indonesia 1.53 3.34 33 Macrol Turkey 0.76 3.33 39 Klaromin Turkey 0.50 3.07 31 Klax Turkey 1.71 2.92 27 Bicrolid Indonesia 1.49 2.81 32 Macrol Turkey 0.70 2.78 19 Crixan India 1.11 2.69 20 Crixan India 1.02 2.66 36 Klax Turkey 0.77 2.55 34 Klarolid Turkey 1.34 2.54 30 Klax Turkey 1.28 2.48 38 Claricide Turkey 0.52 2.45 26 Comtro Indonesia 1.15 2.38 22 Clarithro-250 India 0.52 1.87 35 Klarolid Turkey 0.53 1.86 aIndividual impurities were calculated from the area under the high pressure liquid chromatography peak (peak height for N-de-methyl-6-O-methyl erythromycin A), expressed as % w/w with respect to clarithromycin and summed together for the total.