FORMULATION AND EVALUATION OF SOLID LIPID NANOPARTICLES OF .
International Journal of Pharmacy and Biological SciencesISSN: 2321-3272 (Print), ISSN: 2230-7605 (Online)IJPBS Volume 8 Issue 3 JUL-SEPT 2018 273-288Research Article Pharmaceutical Sciences Open Access MCI Approved UGC Approved Journal FORMULATION AND EVALUATION OFSOLID LIPID NANOPARTICLES OF VENLAFAXINE HYDROCHLORIDEFOR THE EFFECTIVE TREATMENT OF DEPRESSIONSayantan Mukhopadhyay*, Jyoti Nautiyal1 and Preeti Kothiyal2*Department of Pharmaceutics, Division of Pharmaceutical Science, Shri Guru Ram Rai University, Uttarakhand,India.1Department of Pharmaceutics, Shri Guru Ram Rai Institute of Technology and Sciences, Uttarakhand TechnicalUniversity, Uttarakhand, India.2Department of Pharmaceutics, Division of Pharmaceutical Science, Shri Guru Ram Rai University, Uttarakhand,India.*Corresponding Author Email: sayantan.pharmaceutics@gmail.comABSTRACTABSTRACTIn the present study, Venlafaxine hydrochloride-loaded solid lipid nanoparticles were successfully prepared byusing modified solvent diffusion method. The SLNs were prepared by using 1.5% and 2.5% w/v of Tween 80. Theprepared nanoparticles were evaluated for particle size, polydispersity index, zeta potential, surface morphology,drug entrapment and surface entrapment. The particle size of prepared nanoparticles was found in acceptablerange that is from 213.2 to 635.1d. nm and PdI from 0.243-0.947. Along with this zeta potential of all the preparednano formulations lies in the range from –11.2 to – 16.9mV. Low values of surface entrapment efficiency indicatedthat less amount of drug was present on the surface of drug loaded solid lipid nanoparticles and a higher amountof drug was found to be entrapped in drug loaded solid lipid nanoparticles. Finally, carbopol 940 (2%) gel wasprepared by incorporating venlafaxine hydrochloride-loaded solid lipid nanoparticles into it. The prepared gel wasevaluated for viscosity, spreadability, pH and drug content. Drug content of all the prepared solid lipidnanoparticulated gel was ranged from 71.94% to 88.95%. In vitro diffusion results revealed that 64.05% - 90.25%of drug released from the formulations in 24 hrs study period. In formulation FF4 and FF7, by observing the valueof n it was confirmed that the anomalous transport is dominant and in remaining formulations, Super case IITransport is dominant. Therefore, it was concluded that prepared formulation was able to provide bettermanagement of depression and hence improve patient compliance.KEY WORDSBrain targeting, venlafaxine hydrochloride, solid lipid nanoparticles (SLN), particle size, polydispersity index, zetapotential.1. INTRODUCTIONTargeting a drug to a particular site (either organ, tissueor cell) is the main challenge of research ofpharmaceutical industry. [1] Delivery of drug to brain(CNS) is constantly a challenging and inspiring task forthe scientists of research and development sector asInternational Journal of Pharmacy and Biological SciencesBrain is an organ which is the most sophisticated andflexible and is very systematically protected by nature.[2][3]Main problems associated with the delivery of drugs toCNS include:Sayantan Mukhopadhyay* et al273www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci. the poor or lack of proper knowledge about thephysiology of the brain or central nervous system(CNS). [4] Blood Brain Barrier: The accessibility into the brainis prevented by a barrier which is called as BloodBrain Barrier (BBB). [3] BBB generally composed ofendothelial cells which are connected by variousjunctions like adherens junctions (AJ) and by tightjunctions (TJ). Tight junctions of the brain aremainly composed of transmembrane andcytoplasmic proteins. P-glycoprotein (P-gp): It is a type of efflux systemwhich generally pumps out approx. all thexenobiotics along with drug molecule from CNS toblood. [5]In order to overcome these problems, differentstrategies were coming into existence for the effectivedelivery of drug to brain by crossing BBB such asdisruption of blood brain barrier, intracerebral injection,prodrugs, implants etc. [2]There are different CNS disorders like Depression,Alzheimer’s disease, and Epilepsy in which the efficacyof the treatment depends on the amount of drugreaching to its target site that is brain. [6] Depression is amental illness with dejected mood, loss of interest,reduced energy, poor concentration and disturbedsleep or appetite. [7]According to World Health Organization (WHO),“depression will become the second largest illness interms of morbidity by another decade in the world,already one out of every five women, and twelve cal imbalance are the main cause ofdepression. There are mainly three neurotransmitterspresent in brain that are norepinephrine (NE),dopamine (DA) and serotonin (5-hydroxytryptamine rs may responsible for depression. [9] [10]For the effective targeting of drug to target site that isbrain, colloidal system came into existence. Colloidaldrug delivery systems (CDDS) are defined as thevesicular or particulate dosage form whose size is innano range. CDDS mainly include polymericnanoparticles, liposomes, lipid nanoparticles, multipleemulsion, nanocrystals etc. Solid lipid nanoparticulatedInternational Journal of Pharmacy and Biological Sciencesdrug delivery system is one of the Colloidal drug deliverysystems for effective targeting to brain. [11] [12]Solid lipid nanoparticles (SLNs) are the lipid-based nanoformulation whose diameter is in the range from 50 to1000nm. [13] SLNs were developed and invented in earlynineties that is in 1991 and these were the firstgeneration of lipid nanoparticles. [14] [15] Muller and Luckswere first group of researchers who patented thepreparation method of SLN by making use of highpressure homogenization (HPH). [16]Venlafaxine hydrochloride is an antidepressant of theserotonin-norepinephrine reuptake inhibitor (SNRI)class. It is used for the treatment of major depressivedisorder (MDD), panic disorder, generalised anxietydisorder (GAD), and social phobia. [17] Main mechanismof action of Venlafaxine hydrochloride is to inhibit thereuptake of neurotransmitter mainly norepinephrineand serotonin. [18]Literature survey revealed that Venlafaxinehydrochloride loaded SLNs have not been reported untilnow. So, in the present study solid lipid nanoparticles ofvenlafaxine hydrochloride were prepared and evaluatedfor its particle size, PdI, zeta potential, surfaceentrapment and drug entrapment etc.2. METHODS2.1. Methods2.1.1. Preparation of venlafaxine hydrochloride loadedsolid lipid nanoparticlesVenlafaxine hydrochloride loaded SLN was prepared bymodified solvent diffusion method. In this technique,Venlafaxine hydrochloride and monostearin ereaccurately weighed and were dissolved 5ml of ethanolwith heating at 60 C. The prepared organic phase wasthen dispersed into 20 ml aqueous solution containing2.5% w/v Tween 80 solution under mechanical stirrer at1500 rpm for 3hrs in 60 C water bath. The obtaineddispersion was then allowed to cool in roomtemperature. Adjustment of pH was done by 0.1Nhydrochloric acid in order to precipitate SLN. Thedispersion was then centrifuged in 8,000 rpm for 15 minand the product obtained was redispersed in 20 mlTween 80 solution. Composition of differentformulations was given in Table No. 2.1.Sayantan Mukhopadhyay* et al274www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.Table No.2.1: Composition table of different batches of venlafaxine hydrochloride loaded solid en 80Ingredients 1010045052.52.1.2. Particle size, Zeta potential and Polydispersityindex [19] [20]Particle size, Polydispersity index and Zeta potential ofprepared solid lipid nanoparticles was determined byusing Malvern zetasizer at specific temperature that is25 C. For this, different samples were prepared bysimple diluting solid lipid nanoformulation by using thesame dispersion medium as dilution medium.2.1.3. Surface morphology studies [21] [22]External morphology of prepared solid lipidnanoparticles was done by using Scanning ElectronMicroscopy (SEM).In this methods, prepared SLNs were fixed on a stubmade of aluminium with the help of an adhesive tapeand then the nanoparticles were coated using goldunder vaccum. Finally, the gold coated SLNs wereobserved by using scanning electron microscope.2.1.4. Surface entrapment and drug entrapmentefficiency [23]For determination of entrapment efficiency, smallportion of SLN dispersion (approx 5 ml) was taken andcentrifuged for 20min at 18,000rpm (at 20 C). Thesupernatant obtained after centrifugation wasseparated and analysed at 270nm by using UVspectrophotometer. Finally, surface entrapment wasdetermined from simple calculation by usingabsorbance and by using formula, drug entrapmentefficiency was determined.% Drug entrapment efficiency W1 – W2 x 100W1W1 Total weight of drug used during formulation.International Journal of Pharmacy and Biological SciencesW2 Weight of drug obtained in the supernatant aftercentrifugation.2.1.5. Preparation of venlafaxine HCl loaded solid lipidnanoparticulated gel [24]For preparing gel, 2% of carbopol 940 was selected asgelling agent. 2% Carbopol 940 was slowly dispersed in100ml water with continuous stirring for 15-20 min.Then pH of the prepared gel was checked. Finally,appropriate amount of SLN dispersion was slowly added(with continuous stirring at 1000 rpm) to prepare solidlipid nanoparticulated gel.2.1.6. Evaluation of venlafaxine HCl loaded solid lipidnanoparticulated gel2.1.6.1. Viscosity [24] [25]The viscosity of prepared gel was determined by usingBrookfield viscometer at temperature of 37 0.5 C.2.1.6.2. Measurement of pH [25]For measuring the pH of the prepared carbopol gel,approx. 10gm of gel was weighed and put it into 30 mlof volumetric flask. After this, the volume was made upto 30 ml with distilled water. Finally, by using pH meter,pH of the prepared dispersion was measured.2.1.6.3. Spreadibilty study [24] [25]For determining the Spreadibilty of the prepared gel,approx. 0.5gm of the prepared gel was placed in aspecific diameter on a pre-marked glass plate andsecond glass plate was then placed over the glass platecontaining gel. Then a weight of 500gm was appliedover the glass plate for 5 min. Finally, Spreadibilty of thegel was calculated by observing the increase in thediameter which was due to the Spreadibilty of the gel.Sayantan Mukhopadhyay* et al275www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.2.1.6.4. Drug content [26]For the determination of drug content, approximately 1gm of prepared nanoparticulated gel was dissolved inethanol in 50ml volumetric flask. 5ml of the aboveprepared solution was diluted and volume was made upto 25 ml with the help of same solvent that is ethanol.This solution was then used to determine the drugcontent by measuring the absorbance at 270nm withthe help of UV- Visible spectrophotometer.2.1.7. In vitro diffusion study of venlafaxinehydrochloride loaded solid lipid nanoparticulated gel[22]For in-vitro diffusion study, Franz diffusion cell was usedfor the determination of diffusion of drug from the solidlipid nanoparticulated gel. For this, phosphate buffer 7.4was used as a receptor medium. The dialysis membraneused for the study was overnight soaked in the receptormedium which was filled in Franz diffusion cell. Theprepared solid lipid nanoparticulated gel was applied inthe donor compartment of Franz diffusion cell attemperature 37 C 2 C and continuously stirred at 800rpm. After 30 min, 5 ml of sample was withdrawn andimmediately 5ml of fresh medium (phosphate buffer)was added to receptor chamber in order to maintainsink condition. The samples were then analysed by UVSpectrophotometer at 270nm. Finally, by using the dataobtained from UV spectrophotometry, a graph wasplotted between % cumulative drug release and time.2.1.8. In vitro pharmacokinetic study [23]In-vitro pharmacokinetic study of prepared solid lipidnanoparticles was determined by using different kineticequations like zero order, first order, higuchi kineticsmodel, hixon crowell and Korsmeyer – Peppas Model inorder to predict the release of drug (Table No. 2.2.).Table No.2.2. Kinetic models and their GraphsKinetic ModelGraphZero order drug release kineticsBetween % cumulative amount of drug release and timeFirst order release kineticsBetween log % drug release and timeHiguchi release modelBetween % cumulative drug releases and 𝑡Hixon crowellBetween cube root of drug remaining and time (hrs)Korsemeyers peppasBetween log % drug release and log time(hrs)3.1.1. Particle size, Zeta potential and Polydispersityindex3.1. Evaluation of venlafaxine hydrochloride loadedParticlesize, PdI and zeta potential of venlafaxinesolid lipid nanoparticleshydrochloride loaded solid lipid nanoparticles wasevaluated by using Malvern zeta sizer and was reportedin Table no. 3.1., 3.2., 3.3. respectively.Table No. 3.1. Particle size of venlafaxine hydrochloride loaded solid lipid nanoparticlesS.No. FormulationParticle 292.196.751593.38FF8349.298.03. RESULT AND DISCUSSIONInternational Journal of Pharmacy and Biological SciencesSayantan Mukhopadhyay* et al276www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.91069.19357.2379.9FF9FF102.0100.0100.0Table No. 3.2. Polydispersity Index of venlafaxine hydrochloride loaded solid lipid nanoparticlesS.No. Formulation Code Polydispersity Index le No. 3.3. Zeta potential of venlafaxine hydrochloride loaded solid lipid nanoparticlesS.No.Formulation CodeZeta Potential (mV)12345678910FF1FF2FF3FF4FF5FF6FF7FF8FF9FF10- 11.8-12.4- 11.2-12.5- 12.8- 13.1- 13.4- 14.7- 15.0- 16.9From the obtained values of particle size, it wasobserved that formulation FF1, FF2, and FF3 (with 1.5%w/v surfactant) show particle size range from 310.5 to635.1d. nm which indicated a wide range of particle sizedistribution. Apart from these, formulations FF4 to FF10(with 2.5% w/v surfactant) show particle size range from213.2 to 379.9 d.nm. Particle size distribution graph forprepared formulations FF4 and FF5 was shown in Fig 3.1and 3.2 respectively. From all the particles size values itmay be concluded that if the amount of lipid increases,the particle size of the solid lipid nanoparticle alsoincreases.Fig 3.1. Particle Size Distribution graph of Formulation FF4International Journal of Pharmacy and Biological SciencesSayantan Mukhopadhyay* et al277www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.Fig 3.2. Particle Size Distribution graph of Formulation FF5Along with this, it was also observed that amount of surfactant plays an important role in the particle sizedistribution and it was revealed that by increasing the concentration of surfactant, reduction in the size of particleswas observed (Fig 3.3.). It may be due to the fact that the surfactant adsorbs on the surface of solid lipidnanoparticles and prevent the further growth of SLNs during preparation as well as it prevents agglomeration ofSLN and therefore results in the formation of stabilized solid lipid nanoparticles with smaller size. The Z-average(d.nm) of all solid lipid nanoparticulated formulations ranged from 248.7 to 828 d.nm (Fig 3.4.).Polydispersity index of all the formulation was reported in Table No. 3.2. From observed values of PdI it wasrevealed that most of the prepared nano formulations was mid-ranged polydisperse as they were having valuesranging from 0.243-0.596. But there are two formulations FF2 and FF3 in which PdI value is 0.812 and 0.947 whichindicate their polydispersity (Fig 3.5.).Zeta potential of all the formulation was reported in Table No. 3.3. For better stability, the nanoparticles shouldhave zeta potential less than -25mV or greater 25mv. From the experimental values obtained after evaluation, itwas observed that zeta potential of all the formulations lies in the range from –11.2 to – 16.9mV which suggestedthat the formulations were not very stable. But the obtained zeta potential values lie within the range (that is –15mV to 15 mV) which was reported to be effective for delivery of nanoformulation to brain. Therefore, it maybe concluded that the prepared formulations may be used for further study as they were able to cross BBB andeffectively reach to its target site that is brain. Zeta potential graph for prepared solid lipid nanoformulation FF4and FF5 is shown in Fig 3.6. and Fig 3.7.Particle size (d.nm)8001.5 % w/v tween 802.5 % w/v tween 80600400200FF9FF3FF7FF2FF5FF10Formulation codeFig 3.3. Relationship between amount of lipid used during the formulation with obtained particle size (d.nm)International Journal of Pharmacy and Biological SciencesSayantan Mukhopadhyay* et al278www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.Z- Average (d.nm) of prepared solid lipid nanoparticlesZ- Average (d.nm)1000828713.6800600400376.7248.7 255.3 259.8 255.6 277.8352.9269.92000FF1FF2FF3FF4FF5FF6Formulation CodeFF7FF8FF9FF10Fig 3.4. Z-Average graph of prepared venlafaxine hydrochloride loaded solid lipid nanoparticlesPOLYDISPERSITY INDEXPolydispersity Index (PdI)10.80.60.40.20FF1FF2FF3FF4 FF5 FF6 FF7FORMULATION CODEFF8FF9FF10Fig 3.5. PdI distribution graph of prepared venlafaxine hydrochloride loaded solid lipid nanoparticlesFig 3.6.: Zeta Potential Distribution graph of Formulation FF4International Journal of Pharmacy and Biological SciencesSayantan Mukhopadhyay* et al279www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.Fig 3.7.: Zeta Potential Distribution graph of Formulation FF5From observed particle size, PdI and zeta potential values, it was clearly observed that formulation FF1, FF2 andFF3 (that is with 1.5% w/v surfactant) were not suitable for further study as they have large particle size and theirPdI values are very high as compared to other formulations. Therefore, formulation from FF4 to FF10 (that is with2.5% w/v surfactant) were selected for further evaluation.3.1.2. Surface morphology studiesSurface morphology of formulation FF5 was shown in Fig 3.8. SEM analysis of formulation FF5 shows smoothsurface of drug loaded SLN with a slight sphere-shaped.Fig 3.8. SEM image of formulation FF53.1.3.Surface entrapment and drug entrapmentefficiencySurface entrapment and drug entrapment values arereported in Table No. 3.4. and graphs shown in Fig 3.9.and 3.10. respectively. Surface entrapment (%) ofprepared drug loaded SLNs was found in between 0.94%to 3.15% and drug entrapment (%) of prepared drugloaded SLNs was found in between 96.85 to 99.06%.From the calculated values of surface entrapment andInternational Journal of Pharmacy and Biological Sciencesdrug entrapment, it was clearly observed that lessamount of drug was present on the surface of drugloaded solid lipid nanoparticles and a higher amount ofdrug was found to be entrapped in drug loaded solidlipid nanoparticles. Therefore, it may be concluded thatby increasing the amount of lipid during formulation,the drug entrapment increases and surface entrapmentdecreases.Sayantan Mukhopadhyay* et al280www.ijpbs.com or www.ijpbsonline.com
ISSN: 2230-7605 (Online); ISSN: 2321-3272 (Print)Int J Pharm Biol Sci.Table No. 3.
1Department of Pharmaceutics, Shri Guru Ram Rai Institute of Technology and Sciences, Uttarakhand Technical University, Uttarakhand, India. 2Department of Pharmaceutics, Division of Pharmaceutical Science, Shri Guru Ram Rai University, Uttarakhand, India. *Corresponding Author Email: sayantan.pharmaceutics@gmail.com ABSTRACT ABSTRACT
Evaluation of Formulation. WHAT DO WE MEAN BY: ‘PSYCHOLOGICAL FORMULATION’? Some definitions: Formulation is a provisional explanation or hypothesis of how an individual comes to present with a certain disorder or circumstance at a particular-point in time. (Weerasekera, 1996) A formulation is a tool used by clinicians to relate theory to practice . It is the lynchpin that .
Formulation Development and Evaluation of Enteric Coated Tablets of Rabeprazole Sodium B.Rama*, Shalem Raju Talluri, Grace Rathnam Department of Pharmaceutics, C. L. Baid Metha College Of Pharmacy, Chennai Abstract: Rabeprazole sodium is highly acid-labile and presents many formulation challenges and to protect it from acidic environment of the stomach an enteric coated tablet formulation is .
Formulation and evaluation of almotriptan chewable tablets 1V. Anil kumar*, K.L. Deepthi*, 1R. Kalyani, 1B. Padmasri, 2D.Prasanth . in the formulation of a chewable tablet is to obtain a complete profile of the active drug. This usually leads to the most efficient formulation of a stable and quality product as the drug usually dictates the choice of fillers, carriers, sweeteners, flavor .
Ravindran et al. / Formulation and Evaluation IJPCR, Volume 8, Issue 9: September 2016 Page 1306 Tween 80 Figure 1: Fruits of Dimocarpus longan. Formulation 1 Formulation 2 Figure 2: Formulated antioxidant creams The added to a free radical Chemicals 2,2 -Diphenyl-1-picryl hydrazyl (DPPH) was obtained from Sigma Aldrich Co, St Louis, USA .
uniformity of films, surface pH, disintegration time and in-vitro dissolution studies. The formulation F5 has disintegration time of 56 seconds and is more promising and showed drug release of 99.89%; hence formulation F5 was selected as best formulation. Keywords: Oral Films, Metoprolol Succinate, Solvent Casting Method. INTRODUCTION
mixed. Since formulation containing antimicrobial agents as active moiety, it is likely to protect from microbial growth 8, 9. To determine the activity of formulation is subject to study the prepared formulation with standard method called standard cup plate method and the inhibition zone diameters were measured with the help of zone reader.
Citation: Arunadevi Birajdar., et al. "Formulation and Evaluation of Antimicrobial Hair Gel from Abrus Precatorius". Medicon Pharmaceutical Sciences 1.3 (2021): 02-13. Formulation and Evaluation of Antimicrobial Hair Gel from Abrus Precatorius 03 Figure 1: Alopecia. Many herbal products have been praised for their hair growth-promoting activities [10].
documents, EPA is publishing and taking public comment on a problem formulation document to refine the current scope, as an additional interim step prior to publication of the draft risk evaluation for 1,4-dioxane. Comments received on this problem formulation document will inform development of the draft risk evaluation.
