Molecular Weight Effect of Different Grades of HPC Polymer

Molecular Weight Effect of Different Grades of HPC Polymer Introduction Bioavailability enhancement Wet media milling + spray drying Issues have impact on dissolution performance Novelty of the work Objective Material and methods wet stirred media milling Spray dryer Characterization techniques Results and discussion Physical stability of the milled precursor suspensions Drug breakage kinetics Formation of the NCMPs via spray drying of the precursor drug suspensions Impact of different polymers on the drug dissolution from NCMPs PVP-K30 HPMC-E3 HPC-SSL, HPC-SL, HPC-L Molecular weight effect of different grades of HPC polymer on drug dissolution performance and stability It is estimated that a large percentage of newly developed drug compounds have limited bioavailibity due to their poor water solubility and very slow dissolution rate [1]. According to the Biopharmaceutics Classification System (BCS), class II drugs are categorized as poorly water soluble and highly permeable in human body [2]. To achieve the therapeutic efficacy of these drugs it is very essential to enhance the bioavailability by increasing the solubility or dissolution rate. A number of approaches have been developed over the time to resolve this issue. The reduction of drug particles size to sub-micron or nanometer has been one of the most popular and effective approaches of all [3-6]. By reducing the particles size order of magnitude, specific surface area of the particles increased radically and enhances the rate of absorption and dissolution [7, 8], according to the Noyes-Whitney equation [9]. Drug nanoparticles production technologies are classified into Bottom-up or Top-down or combination of both. The bottom up techniques include precipitation using supercritical fluid, liquid anti-solvent precipitation, and evaporative precipitation, where small drug particles are produced from drug molecules dissolved in organic solvent [10, 11]. In case of top-down approaches, the particles are reduced to the nanometer range [11]. High pressure homogenization [5] and wet media milling [3] are included in top-down approaches. To prepare drug nanosuspension, wet stirred media milling (WSMM) has achieved the most popularity because of its effectiveness, robustness, scalability, high drug loading, and low polymer side effects [5, 12, 13]. Due to many advantages of drug solid dosage form, it is the most popular dosage form to the patients/clinicians. To encounter this high demand, drug nanosuspensions are usually converted into nanocomposite microparticles (NCMPs) using different drying techniques and incorporated into standard solid dosage forms such as tablets and capsules [13, 14]. Vacuum dryer [15, 16], spray-freeze dryer [17, 18], spray dryer [19, 20], and fluidized bed [17] are very prevalent and widely used drying tools in the pharmaceutical industries. Among all the drying techniques, spray drying has already got attention due to its energy intensive, continuous and scalable drying process characteristics and ability to produce micro to nano-sized particles with a very narrow distribution within a very short time frame [21]. Albeit particle size reduction is an effective technique for bioavailability enhancement, stability issue has always been critical for the efficacy of the drug products. In the nanosuspension, drug particles start losing their specific surface area by aggregation due to relatively high surface energy and specific surface area and also for enhanced Brownian motion [22]. For the prevention of aggregation in the wet media and having better stability, polymers and/or surfactants are added to the suspension as stabilizers. These stabilizers provide stability by electrostatic or electrosteric mechanisms [22]. Steric stability provided by the polymer is drug specific. Only few polymers can help to reduce the particle size of a specific drug down to nanometers. Therefore, selecting a proper stabilizer for a specific drug is a very complex process and cannot be generalized easily [23]. Thus, having a better insight about the polymer properties is very crucial to figure out the right stabilize r for a particular drug. Molecular weight of the polymer is a very significant property of polymers, which determines the capability for steric stabilization along with solution properties [24, 25], regulates mechanical property of the films [26], and controls the drug release during oral administration [27]. Consequently, optimum MW and polymer concentration may help to get the best stabilization performance during and after milling, and faster drug release from the composites.   Choi et al. [16] investigated the impact of lower range MW (11,200-49,000 g/mol) of hydroxypropyl cellulose (HW) on itraconazole suspension production and their recovery from the drug composites. In that work, HPC was used solely with the same concentration, and dissolution performance study was absent.   Sepassi et al. [28] studied MW effect of two different polymers hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) on the particle size reduction of milled nabumetone and ha lofantrine suspensions; however, drying and dissolution rate were not studied. Li et al. [29] studied the MW and concentration effect of hydroxypropyl cellulose (HPC) on the dissolution performance of poorly soluble drug griseofulvin (GF) in presence/absence of sodium dodecyl sulfate (SDS) as surfactant. In that investigation, drug nanosuspension was coated and dried on to the surface of pharmatose using fluidized bed technique and also determined the optimum concentration and MW effect of HPC for complete release of the drug particles during dissolution. To authors best knowledge, no comprehensive and systematic study has been performed so far to get the insight about the head to head comparison of different polymers performance and MW effect of the same polymer on the suspension stability after milling and during dissolution of NCMPs produced via spray drying. It is known from prior study that the combined use of polymers and surfactants provide a synergistic effect leading to better stability in the nanosuspension than individual stabilizers [30, 31]. Due to the side effects of surfactant, it is always expected to use minimal amount in the formulation. If only the use of polymer can provide substantial stability in the nanosuspension and immediate release of the drugs in the dissolution from NCMPs, then it is more viable than using surfactant.   Therefore, this study aims to develop an understanding of the polymer MW and different polymer effect on the physical stability of Itraconazole nanosuspension and drug dissolution fr om the composites. Itraconazole (ITZ) suspensions were milled in a WSMM and the nanocomposite particles were produced using a co-current spray dryer. Three different polymers HPC, PVP, and HPMC were used at 4.5% (w/w) concentration to see the polymer effect and for MW effect, three grades (SSL, SL, and L) of HPC having different MW were used. Laser diffraction, SEM, UV- spectroscopy, XRPD, and DSC were used to analyze the drug suspension and composite particles. Dissolution test of the NCMPs were performed by a USP II paddle apparatus. Materials Itraconazole (ITZ), is an antifungal drug with a water solubility 0.13 mg/L (at pH-7 and 25  °C), is a sparingly water soluble drug belong to the BCS Class II was purchased from Jai Radhe Sales (Ahmedabad, India) and was used as-received condition. Three different polymers, hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), and polyvinylpyrrolidone (PVP) were used as polymers. Three grades (SSL, SL, and L) of HPC with ~40, ~100, and ~140 kDa molecular weight, respectively, were donated by Nisso America Inc. (New York, NY, USA) and used for steric stabilization. Polymeric stabilizers Methocel E3 grade HPMC and PVP Kollidon 30 were donated by Dow Chemical (Midland, MI, USA) and BASF Corporation (Florham Park, NJ, USA) respectively. Sodium dodecyl sulfate (SDS) is an anionic surfactant used as a wetting agent during dissolution and provide electrostatic stabilization in the suspension, was purchased from Sigma Aldrich (Milwaukee, WI, USA). Zirmil Y grade wear-re sistant yttrium-stabilized zirconia (YSZ) with a median size of 430  µm (400  µm nominal size) was used as the milling media and purchased from Saint Gobain ZirPro (Mountainside, NJ, USA). Methods Wet Stirred Media Milling (WSMM) The presuspension (before milling) was prepared following the same procedure used in Afolabi et al. [32]. All the suspension formulations are tabulated below in Table 1. API (Itraconazole) concentration was kept constant at 10% (w/w) and polymer concentration was 4.5% (w/w) for all the formulation. All the concentrations are reported with respect to deionized water (200g). The formulation with 2.5% (w/w) HPC-SL and 0.2% (w/w) SDS was used as a baseline formulation, because from earlier study it was found to be the optimum for fastest and complete drug release from the composite powders. Prepared drug suspension was milled in a Netzsch wet media mill (Micorcer, Fine Particle Technology LLC, Exton, PA, USA) with 80 ml chamber; 50 ml of the chamber was filled with 400  µm (nominal size) Zirconia beads, which is the milling media and a screen with 200  µm opening was used to hold the beads into the chamber and allowing only the passage of the suspension. A shear mixer (Fisher Scientific Laboratory Stirrer, Catalog No. 14-503, Pittsburgh, PA) was used to prepare the suspension prior to transfer into the holding tank of the miller. The suspension was pumped through a peristaltic pump and was milled under the following conditions: suspension flow rate 126 ml/min, rotor speed 4000 rpm corresponding to a tip speed of 11.7 m/s. To keep the suspension temperature below 35  °C, milling chamber and holding tank both were equipped with a chiller (Advantage Engineering Greenwood, IN, USA).   All the parameters were selected from the earlier work done by Afolabi et al. [31]. To determine the breakage kinetics, particle sizes were measured at different time intervals up to 65 minutes and the suspension were refrigerated at 8  °C for one day before spray drying. Preparation of NCMPs via Spray Drying The prepared nanosuspesions were dried within a day of milling using a spray dryer (4M8-Trix, Procept, Zelzate, Belgium) running in a co-current flow set up. All the operating conditions were taken from Azad et al. [19].The suspensions were atomized at 2 bar atomizing pressure using a bi-fluid nozzle having 0.6 mm tip diameter. In each run, ~120 gm nanosuspensions were sprayed at 1.3-1.6 g/min spray rate using a peristaltic pump (Makeit-EZ, Creates, Zelzate, Belgium). Drying air was fed co-currently from the top of the column at 120  °C temperature and 0.37-0.40 m3/min volumetric flow rate. To avoid sedimentation of the drug particles during spraying, the suspension was stirred using a magnetic stirrer throughout the run. A Cyclone separator was used at 54-70 mbar differential pressure to separate the NCMPs from the outlet air stream and collecting them in a glass jar. The dried powders later on were used for powder sample characterization e.g., XRD, DSC, Rodos, and dissolutio n testing. Particle Size Analysis Particle size distributions of the suspensions were measured at different time interval during milling and after 7-day storage in the refrigerator by laser diffraction (LD) technique using Coulter LS 13 320 (Beckman Coulter, Miami, FL). All the steps involved for measuring PSDs of the suspensions were followed from Li et al. [29]. During sample addition, intensity was maintained between 40-45% while obscuration was below 8%. Mie scattering theory was used to compute the volume-based PSDs in the software. Refractive index value is 1.68 for ITZ and 1.33 for deionized water (medium). Before measuring the PSDs, 2 ml suspension sample was collected from the outlet of the mill chamber and diluted with 5 ml of the respective stabilizer solution using a vortex mixer (Fisher Scientific Digital Vortex Mixer, Catalog no: 0215370, Model No: 945415, Pittsburgh, PA) at 1500 rpm for 1 min. The Particle size distributions (PSDs) of produced NCMPs via spray drying were measured by Rodos/Helos laser diffraction (LD) system (Sympatec, NJ, USA) based on Furnhofer theory with dry powder dispersion module. On the sample chute of the Rodos dispersing system, just about 1 g of the sample was placed. To feed the samples, the sample chute was vibrated at 50% settings and 0.1 bar dispersion pressure was imposed to suck in the falling powder through the sample cell of the laser diffraction system. Determination of Drug Content in the Composite Powders Drug content of the composite powders were measured by assay testing. ITZ solubility is - in dichloromethane (DCM). 100 mg of the NCMPs was dissolved in 20 ml DCM, sonicated for 30 mins to ensure all the ITZ is dissolved in the solvent and then they were allowed to sediment overnight. An aliquot of 100  µl is taken from the supernatant and diluted to 10 ml with DCM. The absorbance of all the samples was measured at 260 nm wavelength via Ultraviolet (UV) spectrophotometer (Agilent, Santa Clara, CA, USA). Six replicates were prepared from each NCMP formulation to calculate mean drug content and percent relative standard deviation (RSD). Scanning Electron Microscopy (SEM) SEM imaging was performed to understand the morphology and particle size of the ITZ particles before and after milling. SEM images of as-received ITZ and baseline formulation was taken using a LEO 1530 SVMP (Carl Zeiss, Inc., Peabody, MA, USA) SEM machine. Approximately, 0.1 ml milled suspension sample was placed on top of a silicon chip (Ted Pella Inc., Redding, CA, USA), and then on top of a carbon specimen holder. The sample was placed into a desiccator for overnight drying. The samples were then sputter coated with carbon before analyzing [33]. X-ray Powder Diffraction (PXRD) The crystallinity of the as-received ITZ, physical mixture of ITZ-excipinets, and spray dried powders were analyzed using PXRD (PANalytical, Westborough, MA, USA), provided with Cu KÃŽÂ ± radiation (ÃŽÂ »= 1.5406 Ã…). The samples were scanned at a rate 0.165 S-1 for 2ÃŽÂ ¸ ranging from 5 to 40 °. Differential Scanning Calorimetry (DSC) DSC of the as-received ITZ, Physical mixture of ITZ-excipients, and spray dried powders was performed using a Mettler-Toledo polymer analyzer (PolyDSC, Columbus, OH, USA). The samples were heated at a rate of 10  °C/min within a range of 25-220  °C under nitrogen gas flow. With the help of the integrated software of the machine, melting temperature Tm and fusion enthalpy ΆHm were determined. Dissolution Testing Dissolution of ITZ from the as-received drug, and spray dried composite powders were determined via a Distek 2100C dissolution tester (North Brunswick, NJ, USA) according to the USP II paddle method.   The dissolution medium was 1000 ml SDS buffer with 3.0 gm/ml concentration at non-sink condition.   The medium was maintained at 37  °C temperature and 50 rpm paddle speed.   The composites were weighed equivalent to a dose of 20 mg of ITZ. Composites were poured into the dissolution medium and manually 4 ml of samples were taken out at 1, 2, 5, 10, 20, 30, and 60 min. Aliquots of the samples were filtered using a 0.1  µm PVDF membrane type syringe filter to avoid any effect of undissolved drug during UV spectroscopy measurement. The absorbance of ITZ dissolved was measured via UV spectroscopy (Agilent, Santa Clara, CA, USA) at 260 nm wavelength. The blank was measured using SDS buffer at the beginning. The amount of drug dissolved was measured using a calibration curve generated from drug concentration vs. absorbance (R2=0.9995 with p Apparent Shear Viscosity of Milled ITZ Suspensions The apparent shear viscosity of the nanosuspension was measured by following the procedure from Afolabi et al. [32], using R/S plus rheometer (Brookfield Engineering, Middleboro, MS, USA). To impart controlled shear rate on the samples from 0 to 1000 1/s in 60 s, a coxial cylinder (CC40) was used. To control the temperature the jacket temperature was kept constant at 25 ±0.5  °C. Drug nanoparticles formation and physical stability of the milled suspensions The formulation of the milled drug (ITZ) suspensions are presented in Table 1. Drug (ITZ) nano suspension was first produced in presence of both steric and an anionic surfactant, SDS (Run 1). Due to the synergistic effect of HPC and SDS [31], Run 1 was used as a baseline to assess the impact of various stabilizers (HPC, HPMC E3, PVP k30, and SDS) in their breakage kinetics and physical stability of the resulting suspensions. This baseline formulation was found to be the optimum formulation from a previous work performed by Meng et al [29]. The molecular weight effect of HPC was then studied in absence of SDS surfactant (Run 2-4) using three different grades of HPC; SSL, SL, and L grades having molecular weight ~40, ~100, and ~140 kDa, respectively. The apparent shear viscosity of all the formulations (Run 1-7) are represented in Figure 1. Formulations with 2.5% (w/w) HPC-SL/SDS, 4.5% (w/w) HPC-SL, and 4.5% (w/w) HPC-L (Run 1, 3, and 4) are showing near Newtonian behavior, indicating the extent of aggregation is very low. Milled drug suspensions stabilized by SDS or polymer alone (except HPC-SL and HPC-L) are showing significant shear-thinning behavior, indicating significant amount of aggregates. References 1.Kesisoglou, F., S. Panmai, and Y. Wu, Nanosizing-oral formulation development and biopharmaceutical evaluation. Advanced drug delivery reviews, 2007. 59(7): p. 631-644. 2.Amidon, G.L., et al., A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical research, 1995. 12(3): p. 413-420. 3.Merisko-Liversidge, E. and G.G. Liversidge, Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Advanced drug delivery reviews, 2011. 63(6): p. 427-440. 4.Panagiotou, T. and R.J. Fisher, Form nanoparticles via controlled crystallization. Chemical Engineering Progress, 2008. 104(10): p. 33-39. 5.Keck, C.M. and R.H. Mà ¼ller, Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. European Journal of Pharmaceutics and Biopharmaceutics, 2006. 62(1): p. 3-16. 6.Mà ¼ller, R., C. Jacobs, and O. Kayser, Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Advanced drug delivery reviews, 2001. 47(1): p. 3-19. 7.Singh, S.K., et al., Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide. European Journal of Pharmaceutics and Biopharmaceutics, 2011. 78(3): p. 441-446. 8.Tanaka, Y., et al., Nanoparticulation of probucol, a poorly water-soluble drug, using a novel wet-milling process to improve in vitro dissolution and in vivo oral absorption. Drug development and industrial pharmacy, 2012. 38(8): p. 1015-1023. 9.Noyes, A.A. and W.R. Whitney, The rate of solution of solid substances in their own solutions. Journal of the American Chemical Society, 1897. 19(12): p. 930-934. 10.Sun, B. and Y. Yeo, Nanocrystals for the parenteral delivery of poorly water-soluble drugs. Current Opinion in Solid State and Materials Science, 2012. 16(6): p. 295-301. 11.Chan, H.-K. and P.C.L. Kwok, Production methods for nanodrug particles using the bottom-up approach. Advanced drug delivery reviews, 2011. 63(6): p. 406-416. 12.Bhakay, A., et al., Novel aspects of wet milling for the production of microsuspensions and nanosuspensions of poorly water-soluble drugs. Drug development and industrial pharmacy, 2011. 37(8): p. 963-976. 13.Van Eerdenbrugh, B., G. Van den Mooter, and P. Augustijns, Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. International journal of pharmaceutics, 2008. 364(1): p. 64-75. 14.Basa, S., et al., Production and in vitro characterization of solid dosage form incorporating drug nanoparticles. Drug development and industrial pharmacy, 2008. 34(11): p. 1209-1218. 15.Kim, S. and J. Lee, Effective polymeric dispersants for vacuum, convection and freeze drying of drug nanosuspensions. International journal of pharmaceutics, 2010. 397(1): p. 218-224. 16.Choi, J.-Y., C.H. Park, and J. Lee, Effect of polymer molecular weight on nanocomminution of poorly soluble drug. Drug delivery, 2008. 15(5): p. 347-353. 17.Wang, Y., et al., A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles. International journal of pharmaceutics, 2012. 424(1): p. 98-106. 18.Cheow, W.S., et al., Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants. International journal of pharmaceutics, 2011. 404(1): p. 289-300. 19.Azad, M., et al., Spray drying of drug-swellable dispersant suspensions for preparation of fast-dissolving, high drug-loaded, surfactant-free nanocomposites. Drug development and industrial pharmacy, 2015. 41(10): p. 1617-1631. 20.Lee, J., Drug nanoà ¢Ã¢â€š ¬Ã‚ and microparticles processed into solid dosage forms: physical properties. Journal of pharmaceutical sciences, 2003. 92(10): p. 2057-2068. 21.Kemp, I.C., Fundamentals of energy analysis of dryers. Modern Drying Technology, 2011. 4: p. 1-46. 22.Kim, C.-j., Advanced pharmaceutics: Physicochemical principles. 2004: CRC Press. 23.Lee, J., et al., Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion. European journal of pharmaceutical sciences, 2005. 24(5): p. 441-449. 24.Adamson, A. and A. Gast, Physical chemical of surfaces. 1997, New York: Wiley. 25.Ploehn, H.J. and W.B. Russel, Interactions between colloidal particles and soluble polymers. Advances in Chemical Engineering, 1990. 15: p. 137-228. 26.Rowe, R., The effect of the molecular weight of ethyl cellulose on the drug release properties of mixed films of ethyl cellulose and hydroxypropylmethylcellulose. International journal of pharmaceutics, 1986. 29(1): p. 37-41. 27.Mittal, G., et al., Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. Journal of Controlled Release, 2007. 119(1): p. 77-85. 28.Sepassi, S., et al., Effect of polymer molecular weight on the production of drug nanoparticles. Journal of pharmaceutical sciences, 2007. 96(10): p. 2655-2666. 29.Li, M., N. Lopez, and E. Bilgili, A study of the impact of polymer-surfactant in drug nanoparticle coated pharmatose composites on dissolution performance. Advanced Powder Technology, 2016. 30.Ryde, N.P. and S.B. Ruddy, Solid dose nanoparticulate compositions comprising a synergistic combination of a polymeric surface stabilizer and dioctyl sodium sulfosuccinate. 2002, Google Patents. 31.Bilgili, E. and A. Afolabi, A combined microhydrodynamics-polymer adsorption analysis for elucidation of the roles of stabilizers in wet stirred media milling. International journal of pharmaceutics, 2012. 439(1): p. 193-206. 32.Afolabi, A., O. Akinlabi, and E. Bilgili, Impact of process parameters on the breakage kinetics of poorly water-soluble drugs during wet stirred media milling: a microhydrodynamic view. European Journal of Pharmaceutical Sciences, 2014. 51: p. 75-86. 33.Li, M., et al., An intensified vibratory milling process for enhancing the breakage kinetics during the preparation of drug nanosuspensions. AAPS PharmSciTech, 2016. 17(2): p. 389-399.

Styrofoam As Glue

AbstractMosquito repellents are essentially required these days. Mosquito coils are one of the cheapest and effective way of avoiding them, but this coils are made up of chemicals which can harm our health. So we thought about making a substitute mosquito coil that is not harmful to our health and that is the Anstor katol a natural and environmental friendly coil.IntroductionBackground of the Study:We chose this project because a mosquito coil made up from natural mosquito repelling plants will remove the health problems caused by commercial mosquito repellents. oregano and lemongrass are easy to find and very common and also if this project succeed this can be profitable for business and can encourage others to look for other use of our country's natural resources.Statement of the problem:Recent studies showed that the smoke generated from burning mosquito coil is of certain health concerns– a person being exposed to the smoke coming from the coil may suffer severe head ache, nausea and vomiting, the condition will be severe among asthmatic patients. The emission of formaldehyde from one burning coil can be as high as that released from 51 burning cigarettes. This is because of the chemicals found in mosquito coils. Making a mosquito coil out of natural ingredients may remove these problems.Objectives:Have an alternative solution to prevent the different kind of diseases that mosquito brings especially dengue fever and not cause another problem. Make use of the natural resources of our country to solve common problems caused by mosquitoes, especially dengue.Significance of the Study:The importance of our project is that we’ll be able to make a mosquito coil that is not harmful to our health and to kill mosquitoes that are vector-carriers of dengue.Scope and Delimitation:This project tackles on making a mosquito coil that is made up of natural ingredients that is not harmful to human health. Our project also tackles the protection of human beings against mosquito bites that cause diseases.Review of Related Literature: Mosquito coil is a Mosquito-repelling incense, it is usually shaped spiral. The coil is usually held at the centre of the spiral, suspending it in the air, or wedged by two pieces of fireproof nettings to allow continuous smouldering. Burning usually begins at the outer end of the spiral and progresses slowly toward the centre of the spiral, producing a mosquito-repellent smoke. A typical mosquito coil can measure around 15 cm in diameter.Oregano is a medicinal herb known for its antioxidant and anti-microbial, anti-parasitic properties. It is used for the treatment of indigestion problems, muscle pain, insect bites, and menstruation symptoms, bacterial and fungal infections. Dried leaves of oregano are commonly used for the therapeutic purposes it contains iron, vitamins, calcium, magnesium, copper, niacin and thiamine.Oregano plant has been used for the treatment of various diseases since thousands of years back. Medical researches reveal that oregano contains antioxidants , anti-m icrobial and anti-parasitic compounds. Considering these medicinal properties, the studies are ongoing to use oregano for the treatment of severe diseases such as cancer, heart  disease and muscular degeneration.An antioxidant nature of oregano is evident from the presence of thymol and rosmarinic acid. These compounds help in scavenging free radicals, thus preventing cell damage and membrane alteration. The amount of antioxidant present in a tablespoon of fresh oregano and a medium-sized apple are the same.The volatile oil carvacrol present in oregano inhibits the growth of bacteria and other parasitic organisms. Some studies found this medicinal herb to be more effective in killing Giardia than the prescription drugs. Oregano supplements are also used for external and internal fungal infections.Herbal tea prepared with oregano helps in alleviation of headache, urinary problems, lung disorders, diarrhea, nausea, vomiting and jaundice. Oregano boiled in plain water can be used as a mouthwash. Gargling with this water can help to prevent tooth infection and sore throat. Oregano oil applied directly to the infected tooth helps in combating toothache. Ground oregano leaves soothe artthrisis pain, insect bites and other skin problems. Its bitter taste and strong aroma help in controlling head lice.Mosquito’s abound in tropical countries like the Philippines. They have been pestering land vertebrates for millions of years. Insecticides are either too harmful to both man and the environment or too expensive for the consumers. The purpose of this study is to create an environment-friendly, safe, effective and cheap mosquito repellant.Weeping willow leaves, tubang bakod seeds, tubang bakod seed hulls, onion peelings and almaciga sap were collected. The solid ones were pulverized and mixed together in three pans in 1:1:1:2:4 ratio. Two of the pans were given different amounts of the oil extracted from tubang bakod seed while the remaining one was given none. T he mixtures were allowed to dry and were tested on mosquitoes for effectivity and on humans for acceptability. The results showed that tubang bakod has a significant repelling effect on mosquitoes.Continue Reading here

Rumored Buzz on Research Essay Topics for College Students Discovered

Rumored Buzz on Research Essay Topics for College Students Discovered Research Essay Topics for College Students - Overview You don't need to find super technical with legal argumentative essays, but make certain to do your homework on what the recent laws about your preferred topic actually say. Locating good essay topics you could discuss effectively and create powerful argumentative essays is a tricky work. Recent argumentative essay topics that are related to society is going to do. In fact, there are many descriptive essay topics out there that it's rather hard to choose only one. Remember your essay is about solving problems, thus a solution ought to be a highlight of the essay. Typically, it's really simple to discover fully free essay, but there exists yet another dilemma for receiving the essay, which you definitely need to have. The topic has to be interesting, the topic has to be essential and finally the topic has to be informative. Still, figuring out the ideal topic for your essay isn't your only concern for a student. When it has to do with writing an argumentative essay, the most essential point to do is to select a topic and an argument you could really get behind. You are able to also restate the ideas which you've discussed in the body paragraphs in order to make your point valid. It is very important to mention that the idea doesn't need to be a good one. You are going to have to choose something to major in, and most schools may want to understand what you like to learn in your spare time. Regardless of the topic you chose to approach , it is better that you share your work with the class or teacher, however scary it could be. The ways students ought to be taught about their well-being. Another reason is to observe how well students argue on unique views and demonstrate understanding of the studied subject. The standard of your topic will decide on the grading of the paper. Our talented writers understand how to pick the best topics and customize to fulfill your teacher's demands. It's possible to go for an intriguing topic from any area of science. Every student who would like to carry out a great academic paper can use mentioned subjects and example argumentative essay to do an outstanding work. It definitely just isn't uncomplicated to create an important essay since it requirements a substantial quantity of your time and comprehension. Some students utilize the very first idea which arrives in their head and work on it, but the outcome isn't successful. You'll get your essay in time and, because you r satisfaction is guaranteed, you won't need to worry! It genuinely is simply not effortless to make an essential essay as it demands a substantial quantity of your time and comprehension. Though a weak, rambling introduction will often signify the subsequent essay also lacks clarity, a great introduction will allow the reader know just what will happen through the paper. An essay can have a great deal of intentions, although the elementary construction of all type of essays will probably be very same. It could have lots of intentions, however the elementary framework of all sort of essays might be exact same. In this kind of situation, it's more convenient to discover ready-made essays and use them as an example. Just since there are lots of solutions for what to jot down about, in addition, you will see distinctive methods of approaching an audio essay. Actually, you're going to be in a position to fulfill while using the author on line and concentrate on your research. Whenever you demand quick assistance by means of your task, contact on-line expert writing service that may prepare an argumentative essay on the subject you want. Curriculum proposal topics is a means to try. Ergo, just if you decide on to purchase custom made essays on the net, choose the very best streaming help Great-writings. For instance, if you want for only a 10-page essay, you're likely to actually will need to include just 5 web pages. An argumentative essay is a certain sort of academic writing. Be conscious of the size it must be and begin writing the narrative essay outline. Regardless of what piece of writing you are assigned at your institution, the comprehensive paper has to be interesting to read.

Essay about Gender Roles in Ancient Greek Society

Gender Roles in Ancient Greek Society Throughout history, the roles of women and men have always differed to some degree. In ancient Greece, the traditional roles were clear-cut and defined. Women stayed home to care for children and do housework while men left to work. This system of society was not too far off the hunter gatherer concept where women cared for the house and the men hunted. Intriguingly enough, despite the customary submissive role, women had a more multifaceted role and image in society as juxtaposed with the rather simple role men played. Morals for the two were also different. Men obviously had the upper hand with women being the traditional passive. For an example, it was quite acceptable for a man to commit†¦show more content†¦As shown, women were considered naturally submissive as in most other old cultures. This is somewhat understandable as women were the ones who bore children and men provided for the family unit. As time progressed, this stereotype was over emphasized into what is portrayed in these plays and poems. Despite this submissive image, Greek women were not considered naà ¯ve, but a pleasurable if a bit foolish kind of a creature. In Aristophane?s play, Lysistrata, this concept is amply portrayed. Most of the women are portrayed, as impulsive individuals while men are carnal gluttons. Notwithstanding this facet of their image women could also be wily as Medea and Lysistrata: ?What is more, you were born a woman, And women, though most helpless in doing good deeds, Are of every evil the cleverest of contrives? The deceitful female is epitomized by the character of Aphrodite in Euripidies?s Hippolytus. Due to having her altar neglected (as in the case of Psyche) she plotted to bring ruin to Hippolytus and all those who loved him. At the end of the play, Artemis plots revenge against Aphrodite (also called Cypris) saying: ?Hush, that is enough! 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