The Study The Effect Of Polymer And Surfactant Concentration On .

Available online at www.scholarsresearchlibrary.comScholars Research LibraryDer Pharmacia Lettre, 2015, 7 chive.html)ISSN 0975-5071USA CODEN: DPLEB4The study the effect of polymer and surfactant concentration oncharacteristics of nanoparticle formulationsPriyanka Saharan, D. C. Bhatt, S. P. Saharan and Kavita BahmaniDepartment of Pharmaceutical Sciences, faculty of Pharmacy, Guru Jambheshwar University of Science andTechnology, HisarABSTRACTThe Aim of the present work was to study the effect of polymer and surfactant concentration on characteristics ofnanoparticle formulations. Nanoparticles were prepared by solvent evaporation method. The preparednanoparticles were characterized by particle size, entrapment efficiency, drug loading. Compatibility study of drugand polymer was carried out by Fourier transform infrared spectroscopy (FTIR). The results of this study showedthat the particle size, entrapment efficiency and drug loading were 295.5nm, 79.61% and 36.78% respectively. Thedrug release from optimized batch was found to be 74.98 % in 10 hrs. In this study Glipizide loaded PLAnanoparticles were prepared successfully and showed promising sustained drug release profile.Keywords: Glipizide, PLA, Nanoparticles, Entrapment efficiency, Diabetes mellitusINTRODUCTIONDiabetes mellitus is characterized by insulin dependency, altered metabolism of lipids, carbohydrates, and proteins,and an increased risk of complications from vascular diseases [1]. Glipizide belongs to the second-generationsulfonylureas that can be used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [2]. Glipizidestimulates secretion of insulin from the β cells of pancreatic islets tissue and increases the number of insulinreceptors and may increase the concentration of insulin in the pancreatic vein. Glipizide is a weak acid (pKa 5.9)and low solubility in water and highly permeable drugs according to the Biopharmaceutical Classification System(BCS class II) [3].As the drug is having low solubility; it dissolves very poorly so it delays the absorption whichindicates that the rate of dissolution is the controlling step for absorption. Glipizide is having good permeability,poor aqueous solubility and poor drug dissolution, which leads to improper absorption and decreased oralbioavailability. So these limitations have to be addressed in order to achieve intended therapeutic effect, which canbe done by preferring nanoparticles approach over others.The main goal in designing of polymeric nanoparticles for drug delivery system is to deliver the drug in controlledand targeted release to the specific site of action at the therapeutically optimal rate [4]. This approach can also offeradvantages such as limiting fluctuation within a therapeutic range, reducing side effects, decreasing dosingfrequency, and improving patient compliance [5].365Scholar Research Library

Priyanka Saharan et alDer Pharmacia Lettre, 2015, 7 (12):365-371The present investigation aims to formulate and characterize PLA controlled release nanoparticles containingGlipizide by solvent evaporation method for improved bioavailability which could overcome the drawbacks ofGlipizide delivery through conventional dosage forms [6].MATERIALS AND METHODSMaterialsGlipizide was purchased from the international test centre, (Panchkula, India) and Poly-D, L-lactide (PLA) from MPBiomedical, LLC. All other chemicals and reagent were used are of analytical grade.Experimental designThe optimization technique was utilized to obtain systematic formulation design in order to minimize the number oftrials, and analyse the response surface to investigate the effect of independent variables on the response [7]. In thisstudy, 32 full factorial design was adopted for optimization of the formulation of nanoparticles. The amount of PLApolymer (X1, mg) and the concentration of PVA (X2, %w/v) were taken at three level (-1, 0, 1) as formulationfactors (Table 1). The particle size (nm), entrapment efficiency (EE) and drug loading (DL) were taken as dependentvariables. Response surface methodology (RSM) was used for the analysis using Design Expert Software (Version8.0.7.1). The software suggested 13 trial runs for the factorial design batches (F1-F13) are shown in table No.2Table No.1Independent variablesX1X2Low ( 1)500.15LevelsMedium (0)1000.30High (1)1500.45Preparation of nanoparticlesPolymeric nanoparticles were prepared by solvent evaporation method. Accurately weighed quantity of drug (50mg)was dissolved in dichloro methan (DCM) and acetone (5ml each) and polymer in DCM (10 ml) separately andadded into the aqueous phase (100 ml distilled water) containing surfactant using magnetic stirrer. The solution wassonicated using a probe sonicator for 6 min. The emulsion was kept on magnetic stirrer for 4-5 hrs at roomtemperature for the evaporation of organic solvent. After that the nanoparticles were collected by centrifugation for30 minutes at 10,000 rpm (Remi, Mumbai).During centrifugation PVA was removed along with decant. Traceamount of PVA present in nanoparticles was removed by washing with distilled water. After washing finalnanoparticles were lyophilized for 48 hrs.Characteristics of Glipizide loaded PLA nanoparticlesParticle size determinationThe particle size of the PLA Glipizide nanoparticles was measured by particle size analyzer (Malvern Zetasizer)[8].Entrapment efficiency (%EE) and drug loading (%DL)The suspension of nanoparticles was centrifuged at 10000 rpm for 30min. The supernatant was analyzed for freeGlipizide at 276 nm spectrophotometrically. The entrapment efficiency was calculated using formula given belowEntrapment efficiency (%) (total amount of the drug amount of the free drug) 100Total drugDrug loadingThe drug loading refers to the percentage amount of drug entrapped in nanoparticles. [9]. The drug loading wascalculated using formula given belowDrug Loading (%) (Amount of drug Unentrapped drug) 100Weight of nanoparticles recoveredFT- IR Studies:FTIR studies were performed to analyze the compatibility studies between the drug and excipients. Peaks ofindividual pure drug and the peak of drug – polymer combination were compared to find out the interactions. IR366Scholar Research Library

Priyanka Saharan et alDer Pharmacia Lettre, 2015, 7 (12):365-371spectra of pure drug and the drug polymer mixture were obtained in KBR pellets method by using IR affinity- FTIRspectrophotometer (Perkin – Elmer BX II) [10].Drug release studiesThe in-vitro drug release studies were performed on nanoparticles formulations using dissolution Test Apparatus,Type-II (paddle type) (stirring speed 100 rpm in 900ml, phosphate buffer pH 6.8 temperature 37 0.5 C. Samplealiquots of 5 ml were withdrawn at specific intervals and replaced with equal volume of fresh buffer solution tomaintain the sink conditions. The samples were analyzed spectrophotometrically at 276 nm against the blank [11].RESULTS AND DISCUSSIONParticle sizeThe results of particle sizes of Glipizide loaded nanoparticles of different batches are shown in table 2. The particlesize of prepared formulations F1 to F13 was found to be in the range of 295.5 – 720.4 nm. From the above results, itwould be inferred that the particle size increases with increase in amount of polymer. The size of polymericnanoparticles was highly dependent on polymer concentration that would be explained in term of tendency ofpolymer to coalesce at high polymer concentration. The increased amount of polymer provided an additional spacefor drug molecules to get entrapped, thus decreasing the total surface area. On increasing the concentration ofsurfactant (PVA), the particle size was found to decrease. This might be due to the tight surface formed by PVAmacromolecular chains at high concentration.Percentage entrapment efficiency and Percentage drug loadingThe entrapment efficiency and drug loading of different batches are shown in table 2. The entrapment efficiency anddrug loading ranged from 50.67- 79.16% and 14.1 - 36.78% which indicated that increase in amount of PLApolymer also decreased the % E.E and % drug loading but increase with increase in PVA concentration. This may bedue to the more compact polymer coat, which limits its entrapment and more time taken for the precipitation ofpolymer which was in higher amount. The percentage entrapment efficiency increased with increase in PVAconcentration, this may be due to more free drug available on the surface of nanoparticles in place of entrapment onthe nanoparticles.TABLE (2): Experimental design of PLA nanoparticles and results for the various measured responsesRunAmount ofpolymer 505050100100Amount 0.150.450.30.30.45Particle size(nm)Y1Entrapmentefficiency (%)Y2%Drug nse surface analysisResponse surface (3 Dimensional) plot showed the combined effect of PLA polymer and PVA surfactant on particlesize of nanoparticles (fig.1).Response surface plot (3 Dimensional) (fig.2 and fig. 3) shows combined effect ofPLA polymer and PVA surfactant on entrapment efficiency and drug loading.367Scholar Research Library

Priyanka Saharan et alDer Pharmacia Lettre, 2015, 7 (12):365-371Design-Expert SoftwareFactor Coding: ActualParticle Size (PS) (nm)Design points above predicted valueDesign points below predicted value720.4277.041295.5800X1 A: Amount of polymer (PLA)X2 B: surfactant(PVA)Particle Size (PS) (nm)7006005004003002000.451500.3751250.3B: surfactant(PVA) (%w/v)1000.225750.15A: Amount of polymer (PLA) (mg)50Fig.1: Response surface plot showing the combined effect of PLA and PVA on particle size of nanoparticlesFig .2: Response surface plot showing the combined effect of PLA and PVA on % entrapment efficiency of nanoparticlesDesign-Expert SoftwareFactor Coding: ActualDrug Loading (%)Design points above predicted valueDesign points below predicted value36.7836.884714.140X1 A: Amount of polymer (PLA)X2 B: surfactant(PVA)Drug Loading (%)3530252015100.451500.3751250.3B: surfactant(PVA) (%w/v)1000.225750.15A: Amount of polymer (PLA) (mg)50Fig.3: Response surface plot showing the combined effect of PLA and PVA on % Drug loading of nanoparticlesFourier Transforms Infrared Spectroscopy (FTIR)The FTIR spectrum of Glipizide, PLA polymer and physical mixture of Glipizide with PLA is shown in fig.4, 5 and6.368Scholar Research Library

Priyanka Saharan et alDer Pharmacia Lettre, 2015, 7 972.01652.82413.50817.82%T 44.571583.72 6.308006001034.061160.27140012001000400.0cm-1Fig 4: FTIR spectrum of 00800600400.0cm-1Fig 5: FTIR spectrum of 686.15 620.461446.371087.55606.701035.46 28002400200018001600140012001000800600400.0cm-1Fig 6: FTIR spectrum of physical mixture of Glipizide with PLA369Scholar Research Library

Priyanka Saharan et alDer Pharmacia Lettre, 2015, 7 (12):365-371Drug release studiesThe drug release pattern of Glipizide loaded nanoparticle is shown in Fig 7. The percentage cumulative drug releasefrom the nanoparticles was found to be in the range of 73.72% to 78.12% in 10 hrs at pH 6.8. From the study it wasobserved that drug release decreased with increase in polymer concentration due to the high viscosity of PLA whichon contact with the dissolution medium, surface of nanoparticles becomes wet and forms viscous gel layers. As theconcentration of PLA increases viscosity of the gel layers increases while the diffusion coefficient of drug decreases.Dissolution profile of nanoparticles in phosphatebuffer (pH 6.8)100% Cumulative release9080F170F260F350F440F530F6201000100300Time (Min.)400200500600700.Fig.7: Drug Release Profile of F1 – F6Dissolution profile of nanoparticles in phosphate buffer(pH 6.8)100% Cumulative 0Time300 (Min.)400500600700.Fig.8: Drug Release Profile of F7 – F13CONCLUSIONGlipizide loaded PLA nanoparticles were prepared by solvent evaporation method with average particle size of295.5 nm, entrapment efficiency of 79.16% and drug loading 36.78%. FT-IR study showed there was no interaction370Scholar Research Library