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Current Trends in Biotechnology and PharmacyVol. 5 (2) 1110-1122 April 2011. ISSN 0973-8916 (Print), 2230-7303 (Online)1119In the present study the influence of oiltype, quantity of oil, type and concentration ofsurfactant on particle size, zeta potential andloading efficiency were studied by using photoncorrelation spectroscopy, HPLC with UVdetector. An essential component of the emulsionis the internal lipid core which constitutes the drugdissolved in oil and is surrounded by a thin layerof non-ionic surfactant. Sesame and olive oils areof vegetarian origin, bio-compatible and being usedas edible oils from ancient times (19, 20).Moreover they are easily available and to ourknowledge carvedilol loaded nano emulsionswere not reported with these oils. Both the oilswere stable at room temperature and they do notbecome rancid like other oils due to the presenceof natural antioxidants. All these reasons motivateto select the sesame and olive oils for the presentstudy. They have blood pressure reducingproperties therefore their quantity was limited to200µl (19). In all the formulations with 100µl ofeither sesame oil or olive oil the drug was depositedat the bottom of the beaker and the drug contentwas found to be less than 50%. This indicatedthat the volume of the oil was not sufficient tohold the entire drug inside. Hence the volume ofoil was increased to 150 µl. In this case no drugwas seen at the bottom of beaker and the drugcontent was drastically increased to 98.93±1.31%which revealed that 150µl of oil was sufficient tohold 6.3mg of carvedilol. With increasing oil phasevolume from 100µl to 200µl, a significant increasein globule size was observed in both the oils andthe results were shown in Fig.1.Surfactants play a major role in thepreparation and stability of NEs. Surfactants forma monomolecular film around the disperseddroplets and there by reduces the interfacialtension and prevent the droplet coalescence. Brij-97 and tween-80 were used as surfactants forthe present study. Though they are non-naturalsurfactants, they do not produce any toxic effectswhen administered orally. The amount ofsurfactant is also important to form rigid filmaround dispersed globules. However use of excessamount of emulsifier can cause decrease inentrapment efficiency, burst release and formationof other colloidal species like liposomes andmicelles and may even cause toxic effects (20).From the table it was evident that with increasingconcentration of surfactant the globule size wasdecreased but the drug content was decreasedand the optimum concentration of surfactant wasfound to be 1.25% in case of brij 97 and 1.5% incase of tween 80.All the nanoemulsion compositions posses’negative zeta potential, this may be due to thenegative charge of fatty acids. The zeta potentialis a measure of the surface charge and isimportant in keeping the droplets in dispersedstate. The particle interactions are also controlledby the magnitude of the apparent surface chargeof the dispersed globules. Torrey et al (2006)reported that, the ZP of particle formulations is avalue of greater than +30mv or lower than -30mvfor ensuring electrostatic stability. However, thissuggested zeta potential cut off point is anexperience based value and cannot be reliablyused to predict the stability of NEs because awide range of absolute zeta potential values (i.e.,1.5, 12.5, 45.5mv) have been reported for SNEDSand NEs (21,22). The zeta potential depends onthe pH of the nanoemulsion. At lower PH valuesthe zeta potential will be positive and at higherpH values it will be negative. The pH of all NEswas in the range of 6.5±0.03 to 6.8±0.03 and wasalso responsible for negative zeta potentials ofNEs.Carvedilol was a poorly soluble and poorlypermeable drug and its Pka at pH 7.4 was 8.8.At this pH the degree of ionization will be almost100% and it is assumed that the rate of solubilityand hence the rate of drug release will beKoteswari Poluri et al
Current Trends in Biotechnology and PharmacyVol. 5 (2) 1110-1122 April 2011. ISSN 0973-8916 (Print), 2230-7303 (Online)1120enhanced. In-order to evaluate this parameterPhosphate buffer saline pH 7.4 was selected asthe diffusion medium to carry out in-vitro drugrelease characteristics. The rate of drug releasealso depends on the solubility and partitioningcharacteristics of the drug in diffusion medium(23). The solubility studies of carvedilol revealedthat the presence of tween 80 in PBS enhanceits solubility in PBS. Therefore PBS containing1% tween 80 was used as the diffusion medium.The in-vitro drug release follows first orderkinetics. The rate and cumulative amount of drugrelease was highest in formulations C14 whichcontains olive oil as the lipid phase. This may bedue to its high drug content, low surfactantconcentration and narrow globule size. Drugrelease from the nano emulsions is also related tothe partition coefficient of the drug in oil/ watersystem. More specifically for efficient transportof the drug from the formulation in to the systemiccirculation, the drug must first pass from the lipidphase to the aqueous phase and then in to thegastro intestinal tract (GIT) lumen. The oil waterpartition coefficient studies of carvedilol revealedthat the logP values of carvedilol in olive oil washigher than that in the sesame oil (23). Thisproperty of olive oil may cause the more amountof drug release from the nano emulsions (C14) inwhich olive oil was used as the oil phase. In X-ray diffraction studies formulation C7 showed twopeaks at right angles. This may be due to the recrystallizationof the drug (13). Transmissionelectron micrographs revealed that the dispersedglobules were spherical and show no signs ofcoalescence of the droplets and precipitation ofthe drug in oil phase or in continuous phase.The in-vivo pharmacokinetic studieswere performed for the formulation C14 whichshowed maximum in-vitro drug release.Pharmacokinetic parameters revealed that theextent of oral absorption and hence oralbioavailability of carvedilol was enhanced withNE compared with that of marketed tabletsuspension. AUC is expected as an indicator ofthe extent of absorption, where as Cmax and Tmaxare considered as estimates of the absorption rate(24).This may be explained by the fact that thepresence of omega-6 and omega-3 PUFA (polyunsaturated fatty acids) in olive oil which areessential fatty acids and are not produced by thehuman body may enhance the rate of oralabsorption (25). The small droplet size, and hencethe large surface area, lymphatic transport throughthe transcellular pathway (26) may also contributeto the increased bio availability.ConclusionCarvedilol loaded Nano emulsions weresuccessfully prepared by high energyemulsification method using sesame oil or oliveoil and non ionic-surfactants Brij 97 and andtween-80. The resultant Nano emulsions possesshigh drug loading efficiency. The in-vitro rate ofdrug release followed first order kinetics. In-vivopharmaco kinetic studies revealed that the rateand extent of absorption of carvedilol was higherwith oral NE compared with that of oral tabletsuspension. Brij 97 was found to be effective nonionic surfactant for the preparation of stable NEsand co-surfactants are not required along withthis.AcknowledgementThe authors acknowledge OrchidPharmaceuticals, Chennai, India for providinggratis sample of carvedilol. The authors alsoacknowledge the Vimta labs management forproviding access for animal studies.References1. Shoaib, A. (2007). Nanotechnology in DrugDelivery: Introduction and RecentDevelopments. The Internet Journal ofNanotechnology. 2.Regeneration in Parthenium argentatum
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(December 7-9, 2011)Venue: Karunya
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