Goossens, A.P.

van Oudtshoorn, M.C.B.

English

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1370LCM 92S.A. MEDICAL JOUR AL(Supplement-Sol/lh African JOl/mal of Laboratory and Clinical Medicine)8 Tovember 196913. igg, E. B., Soffer, L. and Gyermek, L. (1963): J. Pharmacol. Exp.Ther., 142, 13.14. Ur illo. R. C. and Jacobson, J. (1965): Ibid., 148, 247.15. Sigg, E. B. (19-9): Canad. Psychia!. A soc. J., 4, 75.16. Stein, L. in 'odine, J. H. and Moyer, J. H., eds. (1962): Psychoso-matic Medicine. p. 297. First Hahnemann Symposium. Philadelphia:Lea & Febiger.17. Wei sman. A. (1961): Pharmacologi t, 3, 60.I . Axelrod. J. in Varley, H. and Gowenlock, A. H .. eds. (1963): InThe Clinical Chemistr)' of Monoamines. Amsterdam: EIsevier Pub-lishing Co.19. Axelrod, J. in odine. J. H. and Moyer, J. H., eds. (1962): Psycho-somatic Medicine, p. 312. First Hahnemann Symposium. Philadelphia:Lea & Febiger.20. Axelrod, J., Whi'by, L. G. and Hertting, G. (1961): Science. 133, 3 3.21. Dengler, H. J. and Titus, E. O. (1961): Biochem. Pharmacol., 8, 64.22. Glowinski, J. and Axelrod, J. (1964): Nature (Lond.), 204, 1318.23. Van Amerom, \ . F. H .. Daamen, J. L., Hurkmans, J. A. T. M.,M~~ens, G. J. J. and Peters, K. A. (1962): Experienlia (Basel) , 18, 93.24. Anens. E. J. and Slmoms, A. M. (1960): Arch. in!. Pharmacodyn.,127, 479.A COMPARATIVE STUDY OF THE AVAILABILITY OF SULPHAFURAZOLE FROM COM·MERCIAL BRANDS OF SULPHAFURAZOLE TABLETSA. P. GOD SE SAD M. C. B. VA OUDTSHOORN, Department of Pharmaceutics, Po/chefs/room University,Potchefstroom, TvlM---~UmThe following differential equations are propo ed tode cribe Ihe model:A ---Iag .----7) Bk i, IPHARl\.1ACOKINETIC MODELThe following pharmacokinetic model is presented todescribe the kinetics of sulphafurazole absorption, meta-bolism and excretion in man after administration oftablets.6·111·0221·4223·2816· 55D0·5038ooסס·00·53902·49172·28491·62500·10750·10280·10830·03410·04190·03010·14160·14470·13840·IW50·12920·10384·89194·78665·00434·31815·36116·671867·8857·6660·8789·3080·9477·42484736103·806·503·63C0·80461·06790·63865·94500·88672·60550·11750·10880·09740·03460·03590·03240·15210'14470·12980·10190·14160·13114·55414·78965·33606·80224·89235·284654·2758·1458·1515·6319·0119·0930'5353569·9177 ·1577·24102·60Product4'299'18B1'23790·65610·39051·35175·60201·37110'11340'11730'12520·03880·04810·03120·15220·16540'15640·09530'17100·19254·55094'18824·42907·27334·05133·600763·8262·0465·7521·2125·4216·3485·0387·4682·09484828101-701· 5621·7022·5818·57A1·25800·25500·42181·84801· 51372·23440·09870·10030·09990·03630·03750·02880·13500·13780·12870·1565O' 16960·14535·13065·02645·38154·42644·08584·770459·4360·5664·9281·1383·1583·4926262410·02105·00Constal/Is and Sub-other data jecIALag (hr) BLAkt (hr-I) BLAk 2 (hr-I) BLAkg (hr-I) BLAK (hr-I) BLAk. (hr-I) BLElimination half- Alife for free sul- Bphafurazole (hI') LExcretion half- Alife for acetylsul- Bphafurazole (hI') LTheoretical Aamount of free Bsulphafurazole Lexcreted in 48hours (mg.)Theoretical Aamount of acetyl- Bsulphafurazole Lexcreted in 48hours (mg.)Theoretical Aamount of total Bsulphafurazole Lexcreted in 48hours (mg.)Period of urine Acollection (hours) BLContent of sul-phafurazole (%of label claim)Di integrationtime (min.) B.P.-methodHardness of tab-lets (kg.) (Mon-santo hardnesstester)TABLE I. ANALYTICAL DATA, AND RATE A D OTHER co STANTS1 VOLVED IN THE ABSORPTION, METABOLISM A 0 EXCRETION OFSULPHAFURAZOLE I MAN1.2.3.5.4.k. - k.MdA- - -k.AdtdB- = klA - (k,B + k,B)dt= k.A - KBdU- = k,BdtdMdtdUmdtle has been shown by everal authors that the physicalpropertie of a drug, uch a particle size, solubility, dis-olution rate, etc., may have an effect on the biologicalavailability of the drug.]-· In the course of a tudy aimedat the determination of the effect of variables in theformulation of ulphafurazole tablets on the biologicalavailability of this drug, pharmacokinetic parameters forsulphafurazole were determined as part of the preliminaryinvestigation, using 4 brand of local commerciallyavailable sulphafurazole tablets.The tablets were administered after an alkali load inorder to eliminate diurnal fluctuation in urinary pH.ovember 1969 S.A. TYDSKRIF VIR GE EESKU DE(Byvoegsel-Sllid-Ajrikaanse Tydskrij vir LaboralOrillm- ell Kliniekwerk)1371LKW 93,..9>~8<tZ0<::> 71008~~ 80Cl~0608~ 40<t0Z<t 20~Cl"'000"c~c800 ~,.600 ~c~400200TIME CH)Fig. 1. rinary excretion of sulphafurazole (subject A, product B) under controlledalkaline urine conditions after oral administration of 1,000 mg. of drug. 0 = experi-mental values; ..... = free drug (hourly): ---- = free drug (cumulative):-.-.- = acetylated drug (hourly): = acetylated drug (cumulative).where t = time in hours after ingestion of the dose;lag the time interval between ingestion of the dose andcommencement of absorption;A concentration of sulphafurazole in gastro-intestinaltract;B concentration of sulphafurazole in the body:M concentration of metabolites of sulphafurazole inbody;concentration of free sulphafurazole in urine;Urn concentration of metabolites in urine:k, rate constant for the absorption of sulphafurazolefrom the tract into the body:k, rate constant for the excretion of free sulpha-furazole from the body into the urine:k, rate constant for the formation of metabolites ofsulphafurazole:k, rate constant for the excretion of metabolite fromthe body into the urine:K rate constant for the elimination of sulphafurazoleby all processes, i.e. K = k, + k,.Two tablets (1,000 mg. sulphafurazole) were admini-stered, on fasting stomach, to 3 male subject in apparentgood health. 0 ingestion (If food was allowed until atleast 2 hours after the tablets had been taken. Alkalineurine condition were maintained by ingesting approxi-mately 4 G of odium bicarbonate J'5 hour before thetablet were taken, followed by the ame dose every 3hours. rine sample were collected hourly for at lea t thefirst 5' hours after ingestion of the tablets. Thereaftersample were collected at increasing intervals up to thetimes stated in Table I. Treating a sample collected be-fore dosage of the drug as a blank. the urine amplewere assayed for free and total ulphafurazole by theBratton and Marsball method.'RESULT D 01 USStOAnalytical data a well a the computed rate and othercon tants involved in the absorption, metaboli m and ex-cretion of sUlphafurazole are li ted in Table I. Thetheoretical curves, defined by the above equation, forubject A (product B) are hown in Fig. I. The experi-mental value are in close agreement with tho e com-puted from the differential equation, and the propo edmodel may be accepted as uitable to de cribe the kineticof the absorption. metabolism and excretion of ulpha-furazole.The tablets used in the study are of unknown compo i-tion, but differences in the formation, manufacturing pro-cedures, and raw materials used must be as umed a mostlikely becau e the tablet are being manufactured by4 different local pharmaceutical companie . Thi assump-tion is confirmed by difference found in the content of. ulphafurazole. appearance, hardness, average weight, anddisintegration time of the different products. The pharma-cokinetic parameters, on the other hand, show hardlyany differences. In all cases absorption of the drug startswithin a reasonably short period of time, and the peakurinary concentration is reached in 2 - 4 hours. The eli-mination half-life of free drug. on which the do age in-terval is ba ed. is of the same order for all 4 products.ranging from approximately 4 to 5 hours. In the light ofthese similarities. the products should be regarded asequally effective.SU 1MARYUrinary excretion data were used in a comparative study ofthe biological availability of sulphafurazole from 4 commercialbrands of sulphafurazole tablets. The tablets were administeredafter an alkali load. rine sample were assayed for freeand total ulphonamide content and from the experimentalvalues the rate and other constants involved in the absorption,metaboli m and excretion of ulphafurazole were computedby means of differential equations proposed to de cribe apharmacokinetic model. Experimental values were in closeagreement with computed values. The similarity in the pharma-cokinetic parameters of the 4 products hows that there i~very little difference, if any. in the availability of sulpha-furazole from the different brand of tablets, and all 4 pro-ducts can be regarded as equally effective.We wi h to thank ProL J. H. enter for hi as i tance incomputing the re ults. and r A. P. Loiter for his a sislancein this study. This study wa supported by a research grantfrom the CSIR.REFERE 'CESI. Boyd. E. M. and DingwalJ. R. W. (1947): Amer. J. Med. &i .. 213. 5492. Reinhold, J. G., Phillips. F. J. and Flippin. H. C. (1945): Ihid.210. 141.3. Tarasz.ka. M. J. and Delor. R. A. (1969): J. Ph,rlll '1.. 58. 21174 'e! on. E. (19 ): J. Amer. Pharm. AssQC.. Sei. I'd. ~. 007, Bratlon. A. C and Ma"halJ. E K. (1939): J Binl Chem, 128. ,1'

A comparative study of the availability of sulphafurazole from commercial brands of sulphafurazole tablets

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A comparative study of the availability of sulphafurazole from commercial brands of sulphafurazole tablets

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