Sulfonation and Substitution of Poly Vinyl Alcohol with Amino Antibiotics

Transcription

1 Joural of Babylo Uiversity/Pure ad Applied cieces/ No(1)/ Vol(22): 2012 College of ciece/babylo Uiversity cietific Coferece ulfoatio ad ubstitutio of Poly Viyl Alcohol with Amio Atibiotics ProfDrFiryal MA Abeer AM hurooq K Wessal M Kh Departmet of Chemistry, College of ciece, Al Mustasiryah Uiversity Ad Nedhal M Kh Departmet of Chemistry, College of ciece, DiyalaUiversity Abstract Colo specific drugs release were sythesized from modificatio of PVA by sulfoatio of hydroxyl groups were carried out by usigchlorosulfoic acid at 0ºCThe substitutio of sulfoyl group with amio atibiotics such as amoxillie ad cephalexiewere occurred,with high coversio percetage,the ovel prepared drug polymers were characterized by NMR, FTIR ad UV pectroscopies Physical properties were studied ad cotrolled drug release behaviors were studied i differet p values at 37ºC The swellig % were calculated i acidic medium at 37ºC to protected the prodrug polymer from hydrolysis i acidic stomach eviromet, ad let it to hydrolyzed i basic medium of itestial, as specific site It was foud that the rate of release showed depedece o the p of the medium withi the colo p Itroductio Polyviyl alcohol is used as carrier polymer to attachmet of o-steroids, ati- Iflammatory drugs(1)the best approach to prepare polymeric carriers of pharmaceutically active compouds is to modify preformed polymers(2) This method offers the advatage of the availability of wide rage of polymer type,ad also simplicity of the employig of hydrophilic polymers with biodegradablebackboes led to the preparatio of polymers systems for oral or topical admiistratio oe of the limitatio of the reactio o polymers is the fact that the reactivity of the drug o the polymer may be low whe it is directly attached o the mai chais of the polymer(2-5),this may be caused by steric hidrace of the eighborigside groupsmay modified polymer boded with drug were prepared (6-7) Poly(styree sulfoyl chloride) was prepared by modificatio of poly styree with chlorosulfoic acid at(0-5)ºc(8),the the poly (P-N-substituted sulfo amides styree derivatives were sythesized, also sulfo -atio of polystyree has bee studied by a umber of researchers(9,10) Polyhydric sythetic polymers such as poly viyl alcohol are geerally used i pharmaceutical material as ahydrophilic oioic polymer,it has foud may applicatiosas gel carriers diluets ad solubilizers ad widely used i suspesio diffusio matrix ad coatig processig(2) The use of biodegradable ad biocompatible polymers i drug delivery systems has recetly bee attractig cosiderable iterest,for may purpose,the carriers supplied are geerally composed of relatively high molecular weight (11) The ew research(12)icluded the preparatio of sulfoated pheol formaldehyde resi,the substituted with differet amies ad amoxic -illi which could use asdrug polymer i differet applicatios ulfoamides areorgaic sulfur compouds that cotai the radical 2 N 2, they are used as atibiotic to treat bacterial ifectios humas ad aimals (13)ulfoamides work by iterferig with abacteriums productio of folic acid which the bacterial cells eed for eergy ad reproductio sulfoamides are distributed throughout the body ad i the soft tissues(12) ٤٠١

2 Experimetal Materials ad Istrumets Amoxicilli ad Cephalexi were purchased from AldrichPVA,chlorosulfoicacid were obtaied frombd(-nmr) spectra were recorded by himatzu spectrophotometer, thermogravimetric aalysis is usig NETC germatebau Gmbit model TA402 the FTIR spectra were recorded by ahimatzu spectrometeruv spectra were recorded usig himadzu(uv-vis) 160 ulfoatio of PVA (P 1 ) 3gm of PVA (Mw 72000) was solubilized ito 10ml of ahydrous DMF was itroduced i aroud bottomed flask equipped with codeser ad separatory fuel which cotaied chlorosulfoic acid, 4ml was added drop wise with vigorously stirred about 2hrs, the sulfoated PVA was obtaied after evaporated the solvet uder vacuum, washed the polymer with diethyl ether 60%coversio with [µi] =075 dl/g it was dissolved i ethaol ad water Table (1) lists the physical properties ubstitutio of sulfoated PVA ( -P 3 ) (10 g,001 mole) of prepared sulfoated PVA was dissolved i 50ml of DMF ad (001mole)(of solubilized atibiotic such as Amoxillie or Cephalexi i 10ml DMF was added gradually, the mixture was stirred ad heated at 50ºC about 30miThe solvet was evaporated ad clear brow polymerwas obtaied Table -1:Physical properties of poly viyl drug sulfoate (,P 3 ) C 2 C 2 NDrug PolyNo Drug Color Coversio% µ dl/g olubility PºC CCN N White yellow Water Ethaol P 3 C CN Amoxillie N C Yellow brow Water Ethaol Cephalexi ٤٠٢

3 Joural of Babylo Uiversity/Pure ad Applied cieces/ No(1)/ Vol(22): 2012 College of ciece/babylo Uiversity cietific Coferece Cotrolled drug released: 01 gof or P 3 drug polymer was placed i 100 ml of buffer solutio with P11 ad 74 at 37ºCAt periodic itervals 3ml of solutio sample buffer with drawig ad tested at usig UV-Vis-spectrophotometer,the release study was carried out daily for 4daysit was calculated the weight% release of dry respect to time wellig studies: Dyamic swellig studies of were made as follows: or P 3 were swolle i solutio with p11(kcl:cl) at 37ºC to determie the parameters of swellig ad diffusio wolle gels removed from the water bath at regular itervals were dried superficially with filter paper Weighted ad placed i same bath To ivestigate the time departmet swellig behavior of i acidic solutios,we performed dyamic swellig studies The swellig % is calculated from the followig relatio:- %=(M 1 -M o )/M o 100 Where = M o is the mass of dry polymer at time 0 M 1 is the mass of swolle polymer at time t Result ad Discussio The sulfoated of PVA was carried out by usig chlorosulfoic acidas show I the followig equatio C 2 C + Cl 2 P 1 + Drug - N 2 P 1 2 NDrug 0 C C2 C C 2 [,P 3 ] 3 Drug - N 2 = Amoxillie, Cephalexie The prepared drug polymers (,P 3 ) were soluble i water because of the presece of ureacted 3 groups through the backboe of the polymer chais,which could ehaced the solubility i water ad this advatage acts for improvemet of isoluble drugsad the PVA is used ascarrier polymer for attachmetof drug via hydrolytically labile sulfoate bods This behavior of bioactive polymer system have very iterest i this workthe polymeric prodrug couldhydrolysis through chemical bod ad it isslowly release The suggest mechaism of hydrolysis of drug polymer is as show below: P 1 ٤٠٣

4 P 1 NDrug P 1 - NDrug N 2 Drug + P 1 P 1 NDrug + + P 1 + NDrug + DrugN 2 + P 1 P 1 NDrug Drug=Amoxicillie, Cephalexi Fig(1)shows the cotrolled drug release of the prodrug polymer,p 3 i differet p values of hydrolysis was carried out i p 74 is higher tha acid medium due to the more - ucleophilic attack as show i the above mechaismfig (2) FTIR spectrum showed the characteristicabsorptio of 2, which appeared at cm -1 symmetricadasymmetric,the other absorptio was observed at 3300cm -1 due to the N sulfoamidethe absorptio of ureacted was observed at 3450cm -1, ad at 2960cm-1 for C- aliphatic Fig (3) ad (4)FTIR spectrum of ad P 3 revealed the ureacted 3 group at 3450cm -1,the other absorptio was observed at 3300cm -1 of characteristicnabsorptio of sulfoamide, ad υ C= at 1720cm -1 of β-lactam, υ C- aliphatic at 2950cm -1 ad υ C- aromatic is appeared at 3070cm -1 The υc=c aromatic is revealed at 1600cm -1 of pheyl rig Table 2: wellig % of ad P 3 i acidic medium at room temperature No % at 1 day % 2 days % at 3 days % at 4 days P These results idicated the chemical stability of the prepared drug polymers ad P 3 i acidic medium as stomach acidic eviromet to protect the drug polymer from hydrolysisthis advatage ehaced the applicatio uses as a stable coated drug polymer, ad to let the drug polymer to hydrolyzed i a itestial basic medium Also the aim of this work is to sythesized drug substituted polymer which successful for log term drug delivery ad highly desirable situatio ad sustaied released for drug delivery systems with greater specificity of actios Fig(5) showed TGA of the prepared polymers &P 3 which idicated the thermal stabilities raged betwee ºC for ad ºC for P 3 This techique is based o measurig the weight loss as a fuctio of time at costat temperature or as a fuctio of temperature at costat rate of heatig The chage i weight was measured as a fuctio of temperature which gave valuable iformatio about the thermal stability of the ad P 3 polymers which attributed to sulfoamide groups through the back boe of the polymer chais We cocluded from this work that the swellable characteristics of the prepared drug polymers were more water-swellableas a hydrolysis are more reactivity i p 74 tha the acidic medium ٤٠٤

5 Joural of Babylo Uiversity/Pure ad Applied cieces/ No(1)/ Vol(22): 2012 College of ciece/babylo Uiversity cietific Coferece 1 NMR spectrum Fig(6) of P2 was obtaied, DM d6 as a solvet with TM as iteral stadard appeared the followig peaks as show i the polymer structure C C 2 N C C N N ( ) p74 P 3 Weight% drug released Time-day p11 P 3 Weight% drug released Time-day Fig1: Cotrolled drug released of,p 3 ٤٠٥

6 Fig(2):FTIR spectra of PVA(P 1 ) Fig(3):FTIR spectra of ( ) Fig(4):FTIR spectra of (P 3 ) ٤٠٦

7 Joural of Babylo Uiversity/Pure ad Applied cieces/ No(1)/ Vol(22): 2012 College of ciece/babylo Uiversity cietific Coferece Wt loss% P 3 TempºC Fig(5):Thermal aalysis of & P 3 Refereces oudabeh D ad Ali A,ythesis ad ydrolysis of Modified poly viyl alcohols cotaiig Iburofe Pedat Groups, JIraia polym Vol(5) No(3) (1996) arris FW, Medical Applicatio of Cotrolled Release,, ,Eds-CRC Press Boca Rato Fla (1984) Kathry E, Chemical ad Egieerig NewsArticales( Polymer Exploited for Drug)P2-4 (2006) Firyal MA, Abbas NM ad Khudheyer JK,Modificatio of PVP with paracetamol Jof Babylo No(4)(2010) Kotwat V,Maris, Nazwa I,Biodegradable polymers, Idia of PharmciVol(6),P (2007) Firyal MA,Abbas NMad Khudheyer JK,ythesis of paracetamol acrylate ad study of its drug release, the fifth cicoferece, College of ci,babylo Uiversity Vol(5) (2010) Prakash B,Neclima A,ehithV,Ramesh C,Developmet Retetive Drug Delivery system of Cephalexi by usig factorial Desig,ArsPharmJVol50 P8-24(2009) Firyal MA,Emad M ad Abeer AR,ythesis of N-substituted sulfoamide polystyree,jof College of Educatio No(5) P(365)(2010) Turbak,AF,IdEgChemProdResDev1,275(1962) Ardeshir K, DavoodMioo ythesis ad characterizatio of poly (8-hydroxy quiolie- P-styree sulfoate JIraia polymer 16() P (2007) Kazumiohs I,Masara ad iroobu F,New biodegradable polymers ad their applic -atio i drug delivery system, Iteratioal J of Pharmaceutics 81, P31-38 (1992) Firyal MA,Abass TA ad Murtatha A, Preparatio of sulfoamide derivatives of pheolic resis, JEducatio Jof college No(6) P (2011) cheaerma,,aucheherziulmas,ecyclopidia oftechvol(33), Ed(1984), Muche, Uraba ad chwarzebery ٤٠٧