Investigation of Inter polymer Complexation between Carbopol 974 ...

February 2013- April 2013, Vol. 3, No. 2, 1123-1131. E- ISSN: 2249 –1929Journal of Chemical, Biological and Physical SciencesAn International Peer Review E-3 Journal of SciencesAvailable online atwww.jcbsc.orgSection B: Biological ScienceCODEN (USA): JCBPATResearch ArticleInvestigation of Inter polymer Complexation betweenCarbopol 974 P and Different Grades of Polyvinylpyrrolidone and Effects on Swelling Properties,Adhesion Strength and Release RateJyostna S.Patil*, Chandan R.Rane, Yashvant ChikteL.M.C.College of Pharmacy Faizpur, IndiaReceived: 25 December 2012; Revised: 6 February 2013; Accepted: 14 February 2013Abstract: The main purpose of this work was to investigate interpolymercomplexation between carbopol 974P and different grades of polyvinylpyrrolidone(K25,K30,K90,VA/S-630)by studying their water retaining capacity, apparent density,conductivity, pH, FTIR, swelling properties, adhesion strength and releaserate.Interpolymer complexation obtained between CP and all PVP grades but mostexpressively with PVP K90, maximum amount of fresh and dried CP-PVP K90complex obtained at a weight ratio of 1:1.the water retaining capacity of all CP-PVPK90 complexes were above 90%. Increased in CP concentration caused decreased inpH with increase in conductivity for all CP-PVP complexes and apparent density ofthe CP-PVP K90 filtrate was lowest.IR spectrum of the CP-PVP K90 complex issimilar to that of PVP K90. Means CP has interacted with PVP K90.disc of physicalmixture of CP-PVP K90 swelled progressively and reached after 18-25 hr. Adhesionstrength was correlated with concentration of CP. Nevertheless, adhesion strength ofCP-PVP K90 complex was lower than the physical mixture of the pure polymers.Interpolymer complexation was most conspicuous between CP and PVP K90.Keywords:Carbopol 974, Polyvinyipyrrolidone (K25, K30, K90, VA/S630),Interpolymar complex.1123 J. Chem. Bio. Phy. Sci. Sec.B , 2012-2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.INTRODUCTIONPolymers are commonly and widely used as excipients in the design and development of a controlled andor sustained-release product. Depending on the their physicochemical properties, Often, it is notuncommon to use two or more polymers in a formulation to develop pharmaceutically acceptable product.varied structure and chemistry of various polymers that are available for use in pharmaceuticalpreparations, however, may render ample opportunity for them to undergo physical and: or chemicalinteraction in-situ. Such interactions may greatly influence product stability, modify drug release kinetics,Satoh 1 reported that the use of a 3:2 weight ratio of hydroxylpropylcellulose (HPC) and carboxyl vinylpolymer (CP) as excipients in tablets significantly decreased the bioadhesion force and greatly affected thedrug release 1 .) Recently 1 , the interaction of CP with HPMC and sodium carboxymethylcellulose (NaCMC)and its effects on the bioadhesive strength and the release of verapamil have been reported 2,3 . Elegakeyand Elgindy 3 prepared PVP-polyacrylic acid (Carbopol 934, 940, and 941) complexes and demonstratedtheir use in the development of sustained-release drug products 3 . Studies suggested that hydrogen bondingbetween carbonyl groups of PVP and the carboxyl groups of polyacrylicacid may be the driving force forthe complexation between PVP and polyacrylic acid 4-6 . Takayama and Nagai 7 reported that PVP forms a1:1 complex with carboxyvinyl polymer. Gupta et al 2 . reinvestigated the interaction between Carbopol 934and PVP. The degree of complexation Was found to be higher at low acidic conditions, and decreased withincreasing pH of the solution 2 .Carbopol are synthetic high-molecular-weight polymers of acrylic acid that are cross linked with eitherallyl sucrose or allyl ethers of pentaerythritol 8 .Carbopol 974P is used in sustained release tabletpreparations 9 .It has mucoadheisve property, there are some reports on the application of carbopol to theextended release dosage form 9,10 . USP describes povidone as a synthetic polymer consisting essentially oflinear 1-vinyl-2-pyrrolidone groups. Various grades of povidone are used in pharmaceutical formulations,primarily in solid dosage forms (wet granulation process) as a binder 11, 13 .MATERIALS AND METHODSCarbopol 974P was procured from Lubrizol (India), and all grades of PVP (K 25,K 30,K 90,VA/S-630)(linear polymers of 1-vinylpyrrolidine-2-one) were purchased from Ranbaxy (India).The viscosity forPVP K 25,L30,K90,VA/S-630 was 1.7,2.5,55,2.5 mPA.s,respectively.and the molecular weight of PVP K25,L30,K90,VA/S-630 was 9500,56000,1300000,58000 respectively.The chemical structure of carbopoland PVP are shown in Figure 1Method for preparation of polymer complex: 2% aqueous dispersion of CP and PVP K 25 were firstprepared. Appropriate amount of CP and PVP dispersions mixed to obtain and PVP weight ratio of 1:1,3:7, and 7:4(weight fraction of 30%, 50%, and 64% of CP).Total polymer concentration fixed at 2% byweight in each sample. The two polymeric solutions stirred uniformly for 1 hour and filtered. The residueconsisting of CP-PVP complex was collected and weighs to represent the weight of fresh polymer complex(W f ) the complex subsequently dried at 110 0 C until a constant weight obtained. The dried CP _PVPcomplex was ground and sieve through no.60 mesh (250 mm) sieve, while the filtrate was collected and1124 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.kept for further analysis. The water retaining capacity of the complex defined as (W f -W d ) stated as apercentage.PH Measurement: CP and PVP (K25, K30, K90, and VA/S-630) mixtures at different weight ratios wasmeasured using pH meter (Sartorius, JAPAN)Conductivity Measurement: By keeping constant concentration of polymer (2%), conductivity measuredwith a cell constant 1 cm -1 at 25 0 C.(ELCO, Mumbai, India)Measurement of Apparent Density: The apparent densities of the CP and PVP (K25, K30, K90, VA/S-630) and the filtrates of CP –PVP (K25, K30, K90, VA/S-630) complexes (1:1) were determined using apycnometer at 25 0 C.FTIR Measurement: FTIR spectra of CP, PVP K90, CP-PVP K90 (1:1) solid complex were measuredusing KBr pellet method (FT-IR 401, Jasco, Tokyo, Japan) at 25 0 C.Adhesion Strength Measurement: Bioadhesive strength of disc was measured on modified physicalbalance using method described by gupta et al 2 Shown in Figure 2. The goat buccal mucosa used as amodel mucosal membrane and a Krebs solution as a moistening fluid. The experiment repeated for threetimes for each complex. Two-arm balance method reported by Parodi 12 with minor modifications and hehad was also used to check and to validate the results of the modified tensiometry method and thecorrelation between the results obtained from these two techniques was established by Parodi.Fig.2: Modified Physical balance for measurement of Mucoadhesive strengthSTUDY OF SWELLING PROPRETIESPreparing disc of 13 mm diameter containing 250 mg of CP-PVP K90 (1:1) solid complex using an IRHydraulic press, compression force was 10 kN/cm2 with a dwell time of 1 s.The complex disc wassubmerged in glass Petri dish Containing 60 ml of phosphate buffer solution. At different intervalsmeasured the increased diameter of disc with a vernier caliper at 25 o C (50 hr)Differential scanning calorimetry (DSC): Thermal analysis carried out using a differential scanningcalorimeter (DSC 50, Shimadzu Scientific Instruments, MD, and USA). The samples placed in analuminum-sealed pan and preheated to 200 ◦C. The sample was cooled to room temperature and thenreheated from 40 to 450 ◦C at a scanning rate of 10 0 C/minIn vitro drug release study: Drug release study for Acyclovir, which used as model drug. The extendedreleasematrix tablets with a total weight of 250 mg were prepared using a mixture of Acyclovir and CP-PVP K90 complex at 1:1. The mixture compressed using a hydraulic press with a 13-mm diameter. Thecompression force was 10 kN/cm 2 with a dwell time of one second.1125 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.WATER RETAINING CAPACITY AS AFUNCTION OF CP-PVPCOMPLEXES50%CP 30%CP 80%CPWATER RETAINED(%)100806040200CP K25 CP K30 CP K90 CPVA/S630POLUMER COMPLEXFig.2: Water retaining capacity as a function of cp-pvp complexesEffect of apparent density: Following figure indicates apparent density values of pure polymer grades(K25, K30, K90, and VA/S-630) solutions and all CP-PVP (complex) filtrates. There was no significantdifference (p>0.005) in the apparent density values among the various density values. The apparent densityof filtrates of CP-PVP K90 complex was lowest among all the filtrates. The apparent density of filtratesof CP-PVP (K25, K 30, VA /S630) complex was highest than their respective PVP solution.Apparent density as afunction of CP-PVP complexespure carbopol pure pvp filtrates of complexes1.2apparent density (%)10.80.60.40.20CP K25 CP K30 CP K90 CP VA/S630polymer complexFig.3: Apparent density as a function of CP-PVP complexes1127 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.Effect on pH: 2% dispersion of CP,PVP k25,K30,K90,and PVP VA/S 630 has a Ph values of2.9,4.7,3.72,3.7 respectively at 25 0 C. Aqueous dispersion of carbopol exhibited pH values between 2.8to3.2, depending on its concentration. Generally, increase the concentration of CP decreased in pH for all thecomplexes. All the CP-PVP complexes were insoluble in acidic aqueous solution but decomplexationtooke place in basic media (Ph 7), which was adjusted with 2 M NaOH.Effect on Conductivity: Conductivity can be used to indicate and estimate the degree of complexationbetween polymers in aqueous solution. All grades of PVP9 K25, K30, K90, VA /S630 interacted with CP.and conductivity was positively correlated with concentration of CP.Increase in conductivity was observed forCP-PVP K90 complex when the CP concentration wasincreasedfrom 50 to 90%, while below 50% of CP, there wasonly a gradual increase similar to the rest of theCP-PVP complexes. This indicates that at a lowerCP concentration, the insoluble complex was surroundedby poor conducting PVP solution. And At a higherCP concentration, a larger amount of flocculatedinsoluble complexes were obtained, which leads to increasedthe conductivity .means generation of ionsresponsible for conductivity.FTIR spectral analysis: The complexation was most prominent betweenCP and PVP K90, furtherstudies including FTIR spectral analysis, adhesion strength and swelling studies, Release rate were carriedout. The FTIR spectra of CP, PVP-K90 and dried CP-PVPK90 (1:1) complex are given in Figure 4.Fig.4: FT-IR spectra of CP-PVP K 90 Complex, PVP K90, and CP 974P.Effect on adhesion strength: The detachment force (D f ) and work of adhesion (W adh ) of disc preparedfrom physical mixture and solid complexes of the CP-PVP K90 at ratio 1:1 to the goat buccal mucosalmembrane is shown I following table.It was found that D f and W adh were linearly related to CP content. Anincrease in CP content caused an increase in D f and W adh . On the other hand the significant decrease in Df1128 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.and W adh were obtained between disc prepared from physical mixtures and solid complexes of CP-PVP K90, at a fixed CP %(p

Investigation...Jyostna S.Patil et al.IN VITRO DRUG RELEASEFigs. 6 and 7 show the dissolution profiles of Acyclovir from the matrix tablets containing CP-PVP K90complex in pH 6.8 phosphate buffer and pH 1.2 HCl solutions, respectively. The rate of drug dissolutionfrom the CP-PVP K90 complex tablet was extended than that from the individual extended releasepolymer matrix tablet. Polymer tested at pH 1.2. In addition, the rate of drug dissolution from the complextablet in pH 6.8 was extending than that at pH 1.2. This might be due to the Bioadhessive property ofcarbopol 974p at a high pH, which extend the rate of drug release from the tablet. The Carbopol matrixtablet, the rate of drug dissolution was influenced by the pH of the dissolution medium. Almost all thecarboxyl groups will dissociate at pH 6.8 resulting in the formation of a swollen gel. However, thecarboxyl groups of Carbopol Will not dissociate at pH 1.2 resulting in a less viscous hydrogel (Bonacucinaet al., 2004). Therefore, the rate of drug dissolution from the Carbopol matrix at pH 6.8 was slower thanthat of the drug at pH 1.2. The Carbopol/Polyvinylpyrrolidone IPC matrix tablets showed much less pHdependency than the Carbopol tablets. The dissolution profile of Acyclovir from the CP-PVP K90 IPCmatrix tablet was compared with that from the PVP and carbopol.Release study of acyclovir in pH 1.2% drug release8060402000 50 100 150time (mins)CarbopolPVPComplexFigure 6: Release study of acyclovir in pH 1.2Release study of Acycolvir in ph 6.8% drug release1501005000 100 200 300time (mins)carbopolpvpcomplexFigure 7: Release study of Acycolvir in ph 6.81130 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.

Investigation...Jyostna S.Patil et al.CONCLUSIONInterpolymer complexation occurred between carbopol 974 and polyvinylpyrrolidone.but to differentextent for the various grades of polyvinylpyrrolidone. Complexation was most conspicuous between CPand PVP K 90 possibly due to higher viscosity and molecular weight of PVP K90. In addition, the swellingand adhesion properties of the CP-PVP K90 solid complex found to be distinguishable from the physicalmixture of pure polymers.ACKNOWLEDGEMENTThe authors are thankfull to Lubrizol (India) for supplying carbopol 974, and also thankfull to PrincipalLMC College of pharmacy Faizpur. For providing the facilities necessary to carryout the experiments.REFERENCES1. K. Satoh, K. Takayama, Y. Machida, Y. Suzuki, M. Nakagaki,T. Nagai, Factors affecting the bioadhesiveproperty of tablets consisting of hydroxypropyl cellulose and carboxyvinyl polymer, Chem. Pharm.Bull.1989, 37, 1366–1368.2. A.Gupta,S. Garg, R.K. Khar, Interpolymer complexation and its effect on bioadhesive strength anddissolution Characteristics of buccal drug delivery. Drug Dev. Ind. Pharm. 1994, 20, 315–325.3. N.A. Elegakey, N.A. Elgindy, Drug encapsulation by Carbopol-polyvinylpyrrolidone flocculation technique.Sci. Pharm. 1981,49, 434–441.4. T. sutsui, H. Nakano,R. Tanaka,T. Tanaka, Physical Properties of interpolymer complexes from polyacrylic Acid and poly vinylpyrrolidone. Kobushi Ronbunshu, 1978, 35,517–524.5. E.Tsuchida,Y. Osada, H. Ohno, H., Formation of interpolymer Complexes. J. Macromol. Sci. Phys.1980,B17, 683–714.6. N.Saski,T. Yokoyama, The behaviors of intermolecular hydrogen bonds in the poly (acrylic acidpol(vinylpyrrolidone).1984.7. K. Takayama, T. Nagai, Application of interpolymer Complexation of polyvinylpyrrolidone: carboxyvinylpolymer to control of drug release. Chem. Pharm. Bull.1987, 35, 4921–4927.8. Raymond C Rowe, Paul J Sheskey, Sian C Owen.’ Handbook of pharmaceutical Exepients’ fifthedition,2006, 111-113.9. M.M.Meshali,G.M. El-sayed,Y. El-saied, et al.preparation and evaluation of theophylline sustained releasetablets, Drug Dev pharm Ind 1996 ;22 (4):373-376.10. G.V. Betageri,D.V. Deshmukh,R.B. Gupta, Oral sustained release Bioadhesive tablet formulation ofDidanosine. Drug Dev. Ind. Pharm.2001, 27,129-136.11. B. Parodi,E. Russo,G. Caviglioli,S. Cafaggi,G. Bigbardi, Development and characterization of abuccoadhesive dosage form of oxycodane hydrochloride. Drug Dev Ind Pharm,1996, 22 (5):445 450.12. G. Bonacucina, S. Martelli,G.F. Palmieri, Rheological, mucoadhesive and release properties of Carbopolgels in hydrophilic cosolvents. Int. J.Pharm. 2004,282, 115–130.13. S.D. Jones,A.D. Woolfson and A.F. Brown, Tex tural, viscoelastic and mucoadhesive properties ofpharmaceutical gels composed of cellulose polymer, Int. J. Pharm151223-233, 1997*Corresponding author: Jyostna S.Patil; M.Pharm Scholar, L.M.C.College ofPharmacy Faizpur1131 J. Chem. Bio. Phy. Sci. Sec. B, 2013, Vol.3, No.2, 1123-1131.