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Optimization Of Drug Is Of Paramount Importance Biology Essay
Published: Last Edited:
This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.
Drugs were there since ancient times and they will be there till there is life on this planet. However over the years we have learnt that optimization of drug is of paramount importance and in the process; patient safety, convenience, compliance, economic and industrial feasibility are also to be overlooked (Edith M1994).
Oral route has been one of the most popular routes of drug delivery due to its ease of administration, patient compliance, least sterility and flexible design of dosage forms. Conventional drug therapy involves the intermittent dosing of a therapeutic agent that has been formulated to ensure stability, activity and bioavailability of the active pharmaceutical ingredient (API). However, many drugs present difficulties when administered by conventional methods due to toxicity and low therapeutic index problems.
Novel drug delivery systems, are being employed both experimentally and therapeutically to alter the body distribution of drugs with a view to reduce the toxicity of existing drugs and delivering them more efficiently. Controlled-release systems have been designed to maintain plasma drug levels in the therapeutic range and thus minimize the effects of such problems. (Agis K 1992; Stephen BD 2002).The aim and objective in designing a controlled release system is to deliver drugs at a rate necessary to achieve and maintain a constant drug slowly over several hours, to protect the stomach from irritating effects of the drug (Aulton ME 1995).
Basically there are three basic modes of drug delivery (Remington 2000)
Targeted delivery
Controlled delivery
Modulated release
Targeted delivery refers to the systemic administration of drug carrier with the goal of delivering the drug to specific cell types, tissues, organs.
Controlled release refers to the use of delivery device with the objective of releasing the drug in to the patient body at a predetermined rate, or at a specific time or worth specific release profiles.
Modulated release implies of a drug delivery device that release the drug at a variable rate controlled by environmental conditions, biofeedback, sensor input or an external control device.
Controlled drug delivery system can be defined as the one, which releases the drug at a predetermined rate locally or systematically for a period of time i.e. it shows a predictability and reproducibility in the drug release kinetics which shows that the discharge of drug ingredients from a controlled release drug delivery system proceed at a rate profile which are predictable kinetically and also reproducible from one unit to other.
Fig.1: A hypothetical plasma concentration-time profile from conventional multiple dosing and single doses of sustained and controlled delivery formulations
The proportion of drug input into the body or dosing rate is determined by the rate of drug release from the delivery device. Multiple kinetic models and equations can be used to describe the drug release kinetics from controlled-release systems, but formulations that give zero-order drug release in-vivo are widely accepted as ideal form many drug therapies. However, controlled-release products have been studied to produce many different release profiles. Systems exhibiting first-order drug release kinetics are also frequently employed to achieve the goals of controlled drug release therapies. Hence, a zero- or first-order release model is frequently considered while calculating the desired drug release kinetics (Aulton ME,1995 and Gwen MJ,1996).
2.1.1 Single unit dosage forms Single unit dosage forms are the oral delivery systems that consist of one unit that contains a single dose of the drug and is intended to be administered singularly. The most widely investigated example is the monolithic matrix-based tablet (Katznendler 1997, Nellore 1998, Pickler 1998). The advantages of this dosage form include high drug loading and the availability of well-characterized and cost-effective production methods. Drug release from these systems is controlled by a variety of mechanisms, including drug diffusion, tablet erosion, matrix swelling or a combination of these mechanisms. Film-coated and osmogen controlled single unit dosage forms have also been studied for modified release applications (Cao 2004, Zang 2003).
2.1.2 Multiple unit dosage forms These are the solid oral dosage forms which consist of a multiple tiny and discrete particulates, which include mini-tablets, pellets and granules. These systems provide flexibility during formulation development and therapeutic benefits to patients. A significant advantage of multiparticulates is that they can be divided into desired doses without formulation or process changes. They can also be blended to deliver concurrently incompatible bioactive agents or particles with different drug release properties.
Controlled delivery attempts to (Objective)
Sustaining drug delivery at a determined rate by maintaining a relatively steady and stable effective drug levels in the body with minimization of unwanted side effects related with a solution kinetic pattern.
Localize drug action by spatial of controlled release systems into the diseased tissue or organ or adjacent to the organs.
Target drug action to particular target cell type with the help of carriers or chemical derivatization to deliver drugs.
Not all drugs lend themselves to the formulation of extended release product. The important factor that are to be considered in the choices of a drug as a candidate of CR preparations are as follows (The Remington pharmaceutical sciences 2000 ; Sansom NL 1999).
Biological half life
Only drugs with short half biological half lives (2-4hours) make good candidates for CR systems, but larger dose may be required to maintain high release rate. Conversely, drugs which are having long half lives may be administered at fewer recurrent intervals and hence there won't be any benefit in formulating these drugs as prolonged release formulations.
Binding of drugs to tissues
eg: Tissue-bound ACE inhibitors, requires less frequent dosing is desirable, although in -spite of their shorter biological half-lives.
Drugs with irreversible effects
eg: platelet cyclo-oxygenase inhibition by aspirin.
The correlation stuck between response and plasma/blood concentration is comparatively flat or if the dose administered results in concentrations which are in the plasma region of the dose response relationship
eg: Thiazides that are used in treatment of hypertension
The drugs were metabolized pharmacologically to active metabolite(s) which are eliminated slowly than the parent drug
Eg: Quinapril, Trandolapril, Venalafaxine
Therapeutic range
Drugs that are highly potent such as cardiac glycosides should not be considered for CR preparations due to loss in flexibility in dosage regimen and potential sudden dose dumping.
GI absorption
Most CR formulations are dissolution controlled, in which release rate from the dosage form is the rate limiting step. Once the drug is released, it is transferred to blood through the lumen of intestine. Therefore efficient drug absorption from gastrointestinal tract is a prerequisite for oral controlled release dosage forms.
Stability to wide range of GI enzymes, flora and PH
For an orally administered drug, stability in the GI contents is necessary to ensure absolute and reproducible drug input into the body, since drug will be exposed to luminal contents. Unlike conventional dosage forms, a CR formulation is exposed to the entire PH range and enzymes.
c. First pass metabolism
Hepatic metabolism may render a drug unsuitable for oral CR release. This is because systemic availability for such a drug is highly reduced when input rate is small. The desired biopharmaceutic characteristics of drugs to be used in the development of oral CR dosage forms are:
Molecular weight : < 1000
Solubility : > 0.1μg/ml at PH 1 to 7.8
Non ionized moiety : > 0.1% to 11% at PH 1 to 7.8
Apparent partition
Coefficient : 0.5 to 2.0
General absorbability : From all GI segments
Release should not be influenced by PH and enzymes
Stability : stable in GI environment
Less protein binding
2.2.3 Drugs which are not ideal candidates for CR formulations
Extensive first pass metabolism (except prodrugs)
Extremely short elimination half life (low therapeutic index)
Extremely long elimination half life (narrow therapeutic range)
Bioavailability problems and instability in GI environment (Yie Chien 2009)
Potential Advantages of controlled drug therapy (Paulaitis 1983)
Avoid patient compliance problems
Employ less total drug
Minimize or eliminate local side effects.
Minimize or eliminate systemic side effects.
Chronic use leads to reduction in drug activity
Drug accumulation can be minimized during chronic dosing.
Improves efficiency in treatment
The condition can be cured or controlled more promptly and reduces fluctuation of drug levels in blood.
Bioavailability of some drugs can be increased
Limitations of Oral CRDDS
On the other hand oral CRDDS suffer from a number of potential disadvantages:
Relatively poor in-vitro in-vivo correlation and possible dose dumping.
Reduced potential for dose change or withdrawal in event of toxicity and loss of effect due to diarrhea (too fast transit time).
Reasons for Oral CRDDS
There is a clinical need to develop the CR formulations to improve drug therapy over that achieved with their conventional counterparts, especially in the following cases: (Palakodaty 1983)
Short elimination half-life(t1/2) and minimum effective concentration(MEC) required for the therapy. Shorter the half life of a drug, larger will be the fluctuations between the maximum steady state concentration (Cssmax) and the minimum steady state concentration (Cssmin) upon multiple dosing. If MEC is therapeutically required, either frequent dosing of a conventional drug product or development of a CR product is necessary.
Similarly the drugs having reasonably long elimination half life and either wide or narrow therapeutic range may also need to be formulated as CR products mainly for :
Two to three day extension and
Minimize the fluctuations between Cssmax and Cssmin with narrow therapeutic range drugs.
2.3.1 Classification of controlled drug delivery systems
Continuous release drug delivery systems
Dissolution controlled drug systems
Matrix type b) Reservoir type
Diffusion controlled release systems
Matrix type b) Reservoir type
Dissolution and diffusion controlled release drug delivery systems
Ion exchange resin drug complexes
Slow dissolving salts and complexes
PH reliant formulations
Osmotic pressure controlled systems
Hydro-dynamic pressure controlled drug delivery systems
Deferred transit and constant/continuous release drug delivery systems
Altered density systems
High density
Low density
II Mucoadhesive systems
III Size dependent systems
Deferred release systems
Intestinal release drug delivery systems
Colonic release drug delivery systems
2.3.2 Mechanism of drug release
Sustained release tablets are often classified according to the mechanism of drug release. The following are the most common means used to achieve a slow controlled release of the drug from tablets (Aulton ME 2002; Robinson JR 1987 and Gwen MJ 1996).
Dissolution control
Drug transport control by diffusion
Dissolution and diffusion controlled
Erosion control
Drug transport control by convective flow
Ion-Exchange control
A) Dissolution controlled release system
Dissolution controlled extended release system can also be obtained by covering drug particles with a slowly dissolving coating. The release of the drug from such units occurs in two steps, (Lachman L 1996).
The liquid that surrounded the release unit dissolves the coating (rate liming dissolution step )
The solid drug is exposed to the liquid and subsequently dissolves.
The basic principle of dissolution control is as follows. If the dissolution process is diffusion layer controlled, where the rate of diffusion from the solid surface through an unstirred liquid film to the bulk solution is rate limiting, the flux J is given by:
J= -D (dc/dx)
Where D is the diffusion coefficient and dc/dx is the concentration gradient from the solid surface to the bulk solution. The flow rate of material is given by
Dm/dt = - (DA/h) (Cb-Cs) = KA (Cs-Cb)
Where K is the intrinsic dissolution rate constant.
Fig.2: Dissolution controlled release system (a) reservoir and (b) matrix swelling-controlled release systems
Diffusion controlled release systems
Drug release from a diffusion controlled unit mainly comprises of two steps:
The liquid that surrounds the dosage form penetrates the release unit and dissolves the drug, a concentration gradient of dissolved drug is thus established between the interior and the exterior of the release unit
The dissolved drug will diffuse in the pores of the release unit or the surrounding membrane and thus be released, or alternatively, the dissolved drug will partition into the membrane surrounding the dose unit and diffuse in the membrane.
A dissolution step is thus normally involved in the release process but the diffusion step is the rate controlling step (fig.3)
C) Bioerodible and combination of diffusion and dissolution systems
A simple expression describing release from all three of the erodible matrices can be given by
= 1- ( 1- )n
Where n=3 for a sphere, n=2 for a cylinder
Fig 3: Drug release form matrix diffusion controlled-release drug delivery systems with the drug homogenously dispersed in: (a) an erodible polymer matrix; and (b) a hydrophilic, swellable polymer matrix.
Erosion controlled release system
Drug release from an erosion system can thus be described in two steps:
Matrix material, in which the drug is dissolved or dispersed, is liberated from the surface of the tablet.
The drug is subsequently exposed to the gastrointestinal fluids and mixed with (if the drug is dissolved in the matrix) or dissolved in (if the drug is suspending in the matrix) the fluid.
Fig.4: Schematic illustration of the mechanism of drug release from an erosion based matrix tablet
E) Osmotically controlled release systems
Controlled delivery of active agents occurs by with the utilization of osmotic pressure. This system is mainly independent of the physiological factors of gastrointestinal tract and hence can be used for systemic as well as targeted drug delivery of drugs. (Bhosle VA 2002).
Fig.5: Schematic illustration of the mechanism of drug release from an Osmotically controlled release system
F) Ion-exchange systems
Ion-exchange systems generally use resins composed of water-insoluble cross-linked polymers. The drug diffusing rate from the resin is controlled by the rigidity of the resin, diffusional path length and area of diffusion. This system is advantageous for drugs that are highly susceptible to degradation by enzymatic processes.
Now-a-days compressed hydrophilic matrices have become most popular as modified release dosage forms for oral administration. Mainly the hydrophilic swellable polymers used to prolong the drug release, cellulose ethers in particular hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose provoked considerable interest because of its good compression characteristics, including when directly compressed, and have adequate swelling properties that allow rapid formation of an external gel layer controlling drug release. The polymers that have been used widely used for matrix tablets are xanthan gum, guar gum, ethyl cellulose(semi inert), polyethylene oxide(PEO), polyvinyl alcohol(PVA), eudragit RS 100, eudragit RL 100. Rarely used materials are polystyrene, polyvinyl acetate, cellulose acetate, fat compounds like carnuba wax, hydrogenated castor oil etc (Carmen FR 2008).
2.4.1 Functions of polymers in Oral controlled release
For the most part, oral controlled release system utilizes principle such as diffusion, dissolution, and permeation for achieving a constant rate of drug delivery. Polymers are uniquely suited as materials of construction for oral delivery systems.
2.4.2 Polymer properties that affect the release of active substances
A good understanding of polymer properties such as diffusion, solubility and structural considerations is important is important in the selection of materials to be used as system components to regulate the fluxes of active ingredients (Berner B 1991).
The flux of a species migrating through a polymeric given in the following equation.
Flux = Ã- permeability Ã- concentration difference
Diffusivity is the component of permeability that accounts for the geometrical constraints encountered by the diffusing species in weaving across the polymeric film. (Jacobs 1993).
Solubility parameters
In reservoir- type systems, for both monolithic and reservoir-type systems, the addition of a second component, such as a drug solvent, to a polymer can change the strength of polymer intermolecular forces and therefore the physical properties of the polymer. The strength of the intermolecular forces of a polymer is measured by its cohesive energy density (CED). The solubility parameter of a polymer also describes intermolecular forces (Burell H 1975).The relationship between the solubility parameter δ and CED is shown in equation:
Compressed tablets can be prepared mainly by using following methods (The Remington 2000)
Wet granulation method
Dry granulation method
Direct compression
2.5.1 Wet granulation
The active ingredients, diluents and disintegrant are blended well sifted through a screen of suitable fines to remove or break up lumps. The prepared binding agent solution was added with slow stirring, to the powder till the mass gets the dampness or wet mass consistency and is allowed to pass through a 6 or 8 mesh screen.
Moist materials from the wet milling step is placed on large sheets of paper on shallow wire trays and placed in drying cabinets with a circulating air current and thermostat heat control. The dried granules size is further reduced by passing them through a smaller mesh screen (no: 22/44) which gives more uniform granules. The lubricants are added as fine powders after dry granulation. It is usually screened through 60 or 100 mesh nylon cloth to eliminate lumps as well as to increase the covering power of the lubricants. The lubricants are blended with granules very gently, preferably in a blender and weighed quantities were compressed into tablets with the help of a tableting machine or tablet press.
2.5.2 Dry granulation
The active ingredients, diluents (if required) and part of lubricants are blended. One of the constituents must have cohesive property. The powdered material is then "slugged" or compressed into large flat tablets or pellets of about 1 inch diameter. The slugs are then comminuted through suitable mesh screen with the help of hand and by mills for larger quantities. The lubricants remaining is added to the granulation and blended gently and the material is compressed into tablets.
2.5.3 Direct compression
Direct compression involves compression of the tablets directly from powdered material without altering the physical nature of the material itself. It involves only two operations, in sequence, powder mixing and tableting. (James ; Swabick 1994; Wardnop J 1998)
( Mathew 2007, Raghuram Reddy K 2003)
2.6.1 Angle of Repose
It can be done by using funnel method. A funnel is attached to a stand and tip of the funnel is adjusted to a height of 2cm from the ground. Weighed amount of granules were taken and made to pass through the funnel slowly until the heap of granules touches the tip of the funnel. A powdered cone is formed whose diameter is measured and angle of repose is calculated by using the following formula:
Where h = height and r= radius of the powder cone.
2.6.2 Bulk Density
In this both loose bulk density (LBD) and tapped bulk density (TBD) were determined. A specified quantity of granules were taken from each formula and shaken slightly to break the agglomerates if present. Then the granules are transferred into a 10ml measuring cylinder and initial volume is noted. Then the cylinder is tapped for atleast 50times from a height of 2.5 cm with 2 seconds interval and it was continued until no further change in the volume was noted.
2.6.3 Compressibility Index
It can be determined by Carr's Compressibility index.
Carr's index (%) =
2.6.4 Hausner's ratio
It is the ratio of tapped density to bulk density.
Hausner's ratio =
In the evaluation of tablets the physical, chemical and bioavailability properties of tablets should be evaluated. The following are the different properties, which are to be evaluated. (As per USP-2000, IP and BP)
2.7.1 Weight variation
The weight variation test would be satisfactory method for determining drug content uniformity of drug distribution. In practice this test is performed by taking 20tablets, from a batch, weighed at a time and the average weight is calculated. Then the tablet is weighed individually. The percentage deviation can be determined by using the following formula.
% deviation =
2.7.2 Hardness test/ crushing strength
The hardness of tablets from each batch can be tested by using monsanto hardness tester. The tester consists of barrel containing a compressible spring held between two plungers. The upper plunger was then forced against a spring by tuning the thread bolt until the tablet fractures. The force (or) load of fracture was recorded the zero force reading was deducted from it. Oral tablets have a hardness of 4 to 10 kg/cm2 and sustained release tablets have about 10-20 kg/cm2.
It is a measure of tablet strength. The friability is determined by using Roche friabilator. The normal revolution of this friabilator is 25rpm. The friability is determined by:
F = 100Ã- (1-w/w0)
Where w0 = weight of tablets before friability
w = weight of tablets after friability
For conventionally compressed tablets, the limit is 0.5% to 1% of their weight.
2.7.4 Swelling Studies
The drug release mechanism from hydrophilic polymeric matrices involves solvent penetration, hydration and swelling of the polymer, diffusion of the dissolved drug in the matrix and erosion of the gel layer. The diffusion coefficient of drug in the dehydrated polymer matrix is low initially but increases considerably as the polymer matrix imbibes more and more water and forms a gel, as time progresses. The hydration rate of the polymer matrix, and thereby the gel formation depends considerably on viscosity, polymer proportion and to a lesser degree on polymer particle size. (Goyal A, 2009)
2.7.5 Dissolution
In-vitro tablet dissolution is found to be a standardized technique for measuring the drug release rate from a dosage form. The main role of the dissolution test could be summarized as follows
Therapeutic effectiveness is optimized at the time of product development and stability measurement.
To maintain the uniformity among the production lots, regular assessment of production quality is performed.
2.7.6 Dissolution kinetics
Three categories of dissolution test specifications for drug products are described in the guidance. Single point specifications are recommended as a routine quality control test for highly soluble and rapidly dissolving drug products. This comparison method can be employed in evaluating scale-up and post-approval changes such as manufacturing site changes, component and composition changes, equipment changes and process changes. Two-point specifications are suggested for characterizing the quality of drug product and for accepting product sameness under SUPAC-related changes.
Method used to compare dissolution data is :
Model dependent methods (zero order, first order, Higuchi's, Korsmeyer's)
2.8 FACTORS AFFECTING THE ORAL SUSTAINED-RELEASE DOSAGE FORM DESIGN (Gwen JM 1996; Vincent 1996)
2.8.1 Biological Factors
Biological half life and duration of Action
These play a vital role in the consideration of drug for controlled release. The half life (t1/2) of a drug quantitatively describes the elimination rate. Each drug has its own distinctive elimination rate, which is the sum of all elimintion processes, including metabolsm, urinary excrtion, and all other that removes drug permanently from the bloodstream. Compounds with short half lives and shows good activity are excellent candidates for sustained-release preparations, there by the dosing frequency of the drug can be reduced. But, this is limited, in that drugs which have very short half lives and may require excessively large amounts of drug in each dosage unit to maintain sustained effects, forcing the dosage form itself to becom limitingly large.
The absorption characteristics of a drug can significantly affect its suitability as a sustained release product. The compounds that have low absorption rate constants will probably be poor candidates for sustaining systems.
An important factor in the overall drug elimination kinetics is the distribution of drugs into tissues, because it not only lowers the concentration of circulating drug but it also can be rate limiting in its equilibration with blood and extracellular fluid.
Side effects
Margin of safety
Role of Diseased state
Role of circadian Rhythm
2.8.2 Physicochemical Factors
a. Dose size
For orally administered systems, there is an upper limit to the bulk size of the dose to be administered. In general a single dose of 0.5-1.0g is considered maximal for a conventional and sustained release dosage forms.
b. Ionization, PKa and aqueous Solubility
Most drugs are weak acids or bases. Since the unchanged form of a drug preferentially permeates across lipid membranes, it is important to note that the relationship between the PKa of the compound and the absorptive environment. Drugs with uncharged form are advantageous for drug permeation. For many compounds, the site of maximum absorption will also be the area in which the drug is the least soluble.
c. Partition Coefficient
Partition coefficient is generally defined as the ratio of the fraction of drug in an oil phase to that of an adjacent aqueous phase. The partition coefficient of oil-soluble drugs becomes important in determining the effectiveness of membrane barrier penetration.
2.8.3 Factors influencing drug release from matrix systems
The feasibility of formulating a drug into a controlled release drug delivery is dictated by the biopharmaceutical and pharmacokinetic aspects of drug absorption and disposition, which is a composite processes, described by the LADMER (Liberation, Absorption, Distribution, Metabolism, Elimination, and Response) system (Mathena 2004).
Fig.6: Variables influencing the kinetics and mechanism of drug release from matrix tablets
Drug Related Factors
Drug solubility
A drug with high solubility shows faster release, while poorly water soluble (< 0.01 mg/ml) often result in incomplete release because of their poor solubility and dissolution rate in the matrix. Drugs which exhibiting PH-dependent solubility, particularly in the gastrointestinal PH range are poor candidates for matrix-based oral controlled release drug delivery.
Dose/Drug content
Drug with a large dose size (>500mg) are difficult to design into a matrix-based controlled release drug delivery system because of the requirement of high amount of polymers or other matrix formers, along with general excipients.
Molecular weight and size
According to classical Higuchi's model the release rate from a matrix- based controlled release drug delivery is proportional to the square root of the diffusion coefficient, which, in turn, depends on molecular weight and diameter of the solute molecule and the viscosity of the diffusion medium. Drugs with a M.W. >500Da are thought to have poor diffusivity in hydrophilic matrices due to the constrain imposed by the aqueous gel structure.
Particle size and shape
Particle size and shape of the soluble drugs, also influences drug release, mainly because of the difference in effective surface area and thus, the intrinsic dissolution rate.
Polymer related factors
Drug release from the matrix-based controlled release drug delivery depends on drug diffusion through polymers and/or erosion of polymers.
Polymer type
Primarily silicon derivatives have been used for preparation of CR matrix systems, but now the trend has been shifted to use water-soluble or bio-erodible polymers. Drug will be released from a hydrophobic matrix through aqueous pores formed in the drug depletion zone, while drug diffuses across the hydrated gel layer in the case of hydrophilic matrix.
Formulation variables Major variables include are
Formulation Geometry
Geometric factors play an important role in regulating the drug dissolution from matrices for a fixed formulation composition. An eluting medium penetrates at the same rate to a certain depth of tablet, regardless of tablet size, where hydration, polymer relaxation, and molecular rearrangement occur, allowing the formation of gel.
From fig.10 below it can be observed that modulation of the effective surface area gives a scope to achieve the desired rates.
Fig.10: Schematic diagram showing the effect of tablet size on drug release from a hydrophilic matrix; h and H are thickness of small and large tablets, h1 and H1 are thickness after hydration, r and R are radius of small and large tablets.
Processing technique
Binding solvents can significantly influence the drug release from hydrophilic matrices. The degree of swelling and gel forming ability of a polymer changes in the presence of a solvent, however the changes in characteristics of a polymer depend on the type of solvent used during wet granulation process.
Formulation Excipients
Studies of possible interaction between excipients in the solid dosage forms are necessary because these interactions can affect the drug release and bioavailability. The presence of hydrophobic diluents can result in a more resistant gel layer, which reduces the infiltration of aqueous mediums an drug diffusion. The addition of soluble fillers enhances the dissolution of soluble drugs by decreasing the tortusity and, thus, the diffusional path length, while insoluble fillers affect the diffusion rate by blocking the surface pores of the tablet. Incorporating a surfactant may result in an increase in drug release rate through improved wetting or solubilization. Binding agents used during the granulation process coat drug particles and also changes the rheology of the gel layer, leading to retardation in release rates; however the degree of retardation is determined by the swelling and hydrating capacities of the binding agent, amount of binder added and the method of addition
Other excipients such as plasticizers may enhance drug-release rates, which may be due to increased dissolution rate of the plasticized polymer, while generally used lubricants will retard drug release rates because of their hydrophobic nature.
One of the least complicated approaches to the manufacture of sustained release dosage forms involves the direct compression or granulation of blends of drug, retardant material, and additives to form a tablet in which drug is embedded in a matrix core of retardant. (Lachman L 1996; Robinson JR 1996)
Materials used as retardants in matrix tablets
Insoluble inert polymers
Tablets prepared from these materials are designed to be ingested intact and not break a part in GI tract. Eg: polyethylene, poly vinyl chloride, ethyl cellulose, methyl acrylate - methacrylate copolymer.
b) Insoluble, erodable polymers
These form matrices that control release through both pore diffusion and erosion. Release characteristics are therefore more sensitive to digestive fluid composition than to the totally insoluble polymer matrix. Total release of drug from wax-lipid matrices is not possible , since a certain fraction of the dose is coated with impermeable wax films. Eg: carnuba wax in combination with stearic acid, stearyl alcohol, castor wax and triglycerides.
c) Hydrophilic polymers
This group represents non-digestible materials that form gels in situ. Drug release is controlled by penetration of water through a gel layer produced by hydration of the polymer and diffusion of drug through the swollen, hydrated matrix, in addition to erosion of the gelled layer. Eg: methyl cellulose, hydroxyl ethyl cellulose, HPMC, sodium alginate, xanthan gum, guar gum etc.
2.9.1 Types of matrix tablet
Hydrophilic Matrix Tablet
For example sodium carboxymethyl cellulose, methylcellulose, HPMC, hydroxyethylcellulose, polyethylene oxide, polyvinyl pyrrolidine, poly vinyl acetate, gelatin, natural gums etc. several commercial patented hydrophilic matrix systems are currently in use, such as synchron technology and hydro dynamically balanced system. Main advantages of hydrophilic matrix systems are ease of manufacture and excellent uniformity of matrix tablet.
Fat wax matrix tablet
The drug can be incorporated into fat wax granulations by spray congealing in air, blend congealing in an aqueous media with or without the aid of surfactants and spray drying techniques. Eg: polyethylene, ethyl cellulose, glyceryl esters of hydrogenated resins has been added to modify the drug release pattern.
c) Plastic matrix tablets
For example polyvinyl chloride, polyethylene, polyvinyl acetate, vinyl chloride copolymer, vinyllidine chloride, acrylate or methyl methacrylate polymer, ethyl cellulose, cellulose acetate, polystyrene.With plastic material(s) tablets can be easily prepared by direct compression of drug provided the plastic material can be comminuted or granulated to desired particle size to facilitate mixing with drug particles.


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Last month I helped Greyfriars Kirk in central Edinburgh produce a brochure about their successes and future plans. It helped they had access to excellent, high resolution photos of their projects, people and events, so I was able to orchestrate an impactful brochure full of colour and modernity.
Greyfriars Kirk Brochure
Last month saw Clyne Heritage Society take over the running of the Brora Heritage Centre from the Highland Council. As part of this there was some rebranding and publicity required – which TGIADD helped out. An A4 trifold leaflet was given a professional treatment, and a couple of banners designed to help passing cars locate the centre, as it's located off the main road (A9 and part of the North Coast 500 tourist route) near the site of the old colliery.
In January I worked on some large scale illustrations for Helixion Limited, as they needed some banners while attending a conference in Sweden. Keying in with previous materials created by myself for Helixion, the illustrations were created with vector drawing technique. Using vectors to represent the phone, icons and hands, meant the illustrations could be scaled well up beyond the 0.8 m required for use in the banners – without any loss of crispness.
Helixion conference banners


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Multitech Isi4608 Driver Download
Multitech Isi4608 Driver Details:
Multitech Isi4608 File Name: multitech_isi4608.zip
Multitech Isi4608 Driver Version: 7260/sN
Multitech Isi4608 ZIP Size: 120.kb
Manufacturer: Multitech
Scan Status: OK
Multitech Isi4608 special revision for: Windows 7 Ultimate 32 bit, Windows XP Starter Edition 32 bit, Windows 8 Enterprise 64 bit, Windows XP Tablet PC Edition 32 bit, Windows Vista Home Basic 32 bit, Windows Vista Starter 64 bit, Windows XP Tablet PC Edition 32 bit, Windows 8 Pro 64 bit, Windows XP Professional N 64 bit, Windows XP Professional 32 bit, Windows 7 Home Basic 64 bit, Windows XP Media Center Edition 2004 32 bit, Windows 7 Starter 32 bit, Windows 7 Professional 64 bit
Multitech Isi4608 Download Stats:
Direct Downloads: 451
Most Recent Download: 4/23/2017
Managed Downloads: 1840
Most Recent Download: 4/22/2017
Download Mirrors: 5
Current Delay: 22 Seconds
Driver License: General Public License
Direct Download Success Stats:
Reports Issued By 381/451 Users
Success Reported By 77/381 Users
Driver Download Score63/100
Driver Installation Score64/100
Overall preformance Score62/100
Installation Manager Success Stats:
Reports Issued By 1647/1840 Users
Success Reported By 1419/1647 Users
Driver Download Score93/100
Driver Installation Score97/100
Overall preformance Score88/100
1. Direct DownloadSelect your OS and press "Download".
This option requires basic OS understanding.
Select Your Operating System, download zipped files, and then proceed to
manually install them.
Recommended if Multitech Isi4608 is the only driver on your PC you wish to update.
2. Driver Installation Manager
This option requires no OS understanding.
Automatically scans your PC for the specific required version of Multitech Isi4608 + all other outdated drivers, and installs them all at once.
After downloading and installing Multitech Isi4608, or the driver installation manager, take a few minutes to send us a report:
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1270 Eagan Industrial Road
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Dec 20, 2016: With demand for fine pixel pitch LED displays rising in the global as well as China market, several China-based and Taiwan-based LED packaging service providers are expanding their production capacities to meet the rising demand.
The global fine pixel pitch LED display market is expected to generate revenue of $3.1 billion by 2024, increasing from $677.1 million in 2015. This means that the market will hit 15.8% CAGR from 2014 to 2024.
On the other hand, China's market value for fine pixel pitch LED displays grew from CNY1.55 billion (US$247 million) in 2015 to CNY4.65 billion in 2020.
Also Read: Global fine pixel pitch LED display market to grow at 15.8% CAGR
China-based LED packaging service providers are focus on 1010 and 0808 packaging for fine pixel pitch LED displays. In 2016, Foshan Nationstar Optoelectronics, a China-based LED packaging service provider, expanded 0808 and 1010 packaging capacity for LED displays with fine pixel pitches of 1.5-2.0mm. In 2017, it will start using 0606 packaging in LED displays with smaller pitches between LED chips.
In 2017, MLS will expand its LED packaging capacity by 50%. The rest of the 50% capacity will be used to manufacture fine pixel pitch LED displays. In the third quarter of 2016, MLS had expanded monthly capacity from packaging 50 billion LED chips to 60-70 billion units at the end 2016.
Also Read: Shuji Nakamura to help make China a global laser hub
Taiwan-based vendors are also not far behind. Taiwan-based leading manufacturer Everlight Electronics is capable of 0606 or 0505 packaging for high-end LED displays with pixel pitches of below 1mm.
In 2017, China-based LED epitaxial wafer and chip makers will have about 230 MOCVDs, and their combined LED chip production capacity will account for over 50% of global total.


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Back issues
Click here to view this and all previous issues on-line.
Quote of the month
Coming together is a beginning.
Keeping together is progress.
Working together is success.
- Henry Ford
Next month's feature:
10 Tips for Being a Great Leader
In this issue:
Welcome to Living the dream, Blue Sky Coaching's monthly e-zine, written for small business owners, young entrepreneurs and service industry professionals and filled with cutting edge success tips to help you skyrocket your income, enjoy more personal time off and be known as a star in your field.
If you enjoy receiving Living the dream e-zine, please pass it on to anyone else you think might like to receive it too. Every 50th subscriber will receive a $50 Myer gift card and so will you, if you were responsible for referring them.
You can read all previous issues of Living the dream e-zine any time at: www.blueskycoaching.com.au/ezine.
Hi! from Tania
Hi there,
Guess what? No, our renovations aren't done yet. Don't be ridiculous! I knew 2 weeks was a long shot, given tradesmen were involved - don't get me started about tradesmen! They've given me lots of ideas for a future Top 10 Tips for Tradesmen article though, like: Tip one - buy a watch; and Tip two - don't park your truck directly behind our driveway. At least Jake's enjoyed playing on the back of their work vehicles.
My big news is I now own my dream oven! That might not sound like a big deal if you're not a 'foodie' like me, but I'm very excited. It's meant some delays to our renovation project (OK, it's my fault), but they've been worth it to have my dream oven.
I also received a beautiful Dura coffee machine for Mothers' Day. Spoilt aren't I? Not that we can use it yet until the tradesmen put our benchtops back on. I'm sure that will happen some day soon, just no idea when.
Warm wishes,
Tania Basheer - Publisher
Living the dream e-zine
Feature: 10 Things to Delegate to Your Team
So many business entrepreneurs and managers are really busy because they're failing to delegate effectively to their team members. I've also found business owners and executives to be reluctant to delegate because they think this means letting go of control (yes, some of them are control freaks) over what happens.
Not so! By delegating effectively to your staff, you'll be able to let go of the burden of doing everything yourself and gain more control over how you spend your time to get the best results for your business.
What does effective delegation mean? It's giving your team the freedom to get a job done without breathing down their necks; providing them with the right level of support to get the job done well (including the resources, information and training they need); clearly communicating expected results to them and holding your team members accountable for producing those results.
Note: To delegate effectively, it's also important to know what not to delegate. Here's a simple question to ask yourself before you delegate anything: If I delegate this activity, duty, item, project or task to one of my team, will the time spent in providing them with the guidance and support they need to do it pay off later/over time in increased productivity, in how the business functions, or in a better use of my time? If yes, delegate it. If no, don't!
Here are 10 things related to the day-to-day operations of your business that I recommend you start delegating to your team (in-house or virtual) as soon as possible:
What will you gain in return for your investment in delegating? Increased productivity, staff development and increased engagement, more assistance and coverage, new creativity and solutions, and better use of your time so you can be the great leader your team needs you to be.
If you'd like some assistance in developing your delegation muscles and in successfully building a coaching culture in your business or organisation, please call me on (08) 8338 3134 or 0411 471 941 or email me at email@example.com. I'd love to help you do that!
For more business, executive or life coaching tips and strategies to help you achieve your goals and create and live the life you've always wanted, visit: www.blueskycoaching.com.au/ezine/index.php. To find out more about how you can work with me personally, visit: www.blueskycoaching.com.au, or call me on (08) 8338 3134 or e-mail me on firstname.lastname@example.com.
Hire the Right Team Members
Would you like easy access to an inexpensive, but highly effective and simple-to-use tool to help you hire the right team members?
A few years ago I discovered a great online Australian behavioural assessment tool called MyProfile. See www.myprofile.com.au
I've used it with many of my business and executive coaching clients for the past five years to help them identify their own strengths and weaknesses and to select the best people for their teams. It can also be used to help with writing effective employment ads and job descriptions that ensure you attract the right kind of applicants.
MyProfile is also a great tool to use to improve communication within a workplace.
Call me on 0411 471 941 or (08) 8338 3134 if you'd like to discuss how I can assist you personally with MyProfile, including conducting an in-house workshop for your organisation or team.
Cut Your Stress Levels in Half in Less Than 5 Minutes with EFT!
Don't believe that's possible? Well it is! I've proved it on many occasions, from a telecall of 10 people, through to conference groups of over 100 and 200 participants. And, best of all, EFT takes just a few minutes to do and is a technique that you can have at your fingertips to use anywhere, anytime that you need it.
I love this breakthrough technique because it's a painless way to address the causes of stress, without going into the details, and it eliminates the associated emotional charge, fast.
Visit www.blueskycoaching.com.au/energytapping.php to find out how you can learn EFT any time through one of my DVD or downloadable EFT packages, or call me on (08) 8338 3134 or 0411 471 941 to arrange a one-to-one session with me or a workshop session for your group or team.
Autumn Special Competition - Be Quick! Drawn 31 May
To enter my Autumn website competition, simply click on the competition image, or visit: http://www.blueskycoaching.com.au/special.php for your chance to WIN a 90-minute business coaching session with me plus a copy of Secrets of Entrepreneurs Under 40 Exposed! by Dale Beaumont, together valued at over $250!????
In Secrets of Entrepreneurs Under 40 Exposed! you'll discover the amazing stories of fourteen dynamic entrepreneurs, how they think, and their unique insights into what it takes to succeed in business.
Next Month: 10 Tips for Being a Great Leader
Great leaders bring out the best in others. They also improve the thinking of the people around them without telling anyone what to do.
Next month, we'll look at ten tips for being a great leader, to help you improve your own as well as your team's performance.
Sponsors and Advertisements
The Savings and Loans Ecoliving Expo is the best place to start for sustainable living ideas and information.
There are ideas, displays and four speaker areas.
Find out about:
Special guest presenter Kim Syrus from Channel Nine's Garden Gurus will be speaking on Saturday and on Sunday, see Brendan Moar from the Lifestyle Channel's Dry Spell Gardening.
When: Saturday 31 May and Sunday 1 June
From: 10 am - 5 pm daily
Entry: Adults $10, Concessions $8, children free!
To WIN your tickets, email Tania on email@example.com by 2 pm on Wednesday 28 May with 'expo tickets please' as your subject and how many tickets you'd like to WIN.
Where: Ridley Centre, Adelaide Showground
For the full program visit www.ecolivingexpo.com.au.
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For more information call Mark Abraham at Crackerjack Computing on 0417 414 363 and visit us at www.crackerjack.net.au.
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Reading this ad? Then why not place yours here. Do you have a product, service or special offer that you'd like to let hundreds of entrepreneurs, SOHO business owners, busy professionals and business executives know about? To find out more about advertising in this e-zine and to reserve your spot for next month, e-mail Tania your details today at firstname.lastname@example.com and include 'e-zine ad' in the subject line.
Advertising Disclaimer: Blue Sky Coaching does not endorse or represent the accuracy or reliability of any of the advertisements included above or the quality of goods, services or information obtained by you in connection with engaging the services of or purchasing goods from the above suppliers.


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Janine Ellenbeck's Profile
Torn West is a culmination of my personal views on color, print, and design.
This self venture serves the simple purpose of bringing timeless, beautiful, and well crafted clothing at an affordable price.
"Fashion fades, style is eternal" YSL
- Female
- Born on January 9
- Joined July 7, 2010
Favorite materials
Cotton, Silk, Wool, Boucle, Denim, Knit, Bamboo, Waxed Canvas, Leather, Metal, Watercolors, Ink
- Janine Ellenbeck
Portland, Oregon,
United States


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Sermon Complete the Test / Become a Member of Christ's Army Neal Parker
Basic Underwater Demolition Course Seeds Planted Seeds Planted –Already among those in top physical condition and highly qualified –Among the annual 650 volunteers from 650 volunteers from Allied navies, Allied navies, only ¼ complete only ¼ complete the course the course
Endurance & Motivation Ultimate Test Ultimate Test –Training is the some of the most inconvenient and unconventional manners –Successful students pace themselves and stay focused on their purpose or become "drop outs" like ¾ of their follow students
Weakness & Strength Brings out unsuspected Weakness & Hidden Strength Brings out unsuspected Weakness & Hidden Strength –Upon success completion of the course, SEALS feel an unbroken bond that past warriors
Final Lesson "You Push Yourself To What You Once Thought Were Your Limits, Then You Keep On Pushing – And You Never Quit"
Leviticus 23:23-25 Leviticus 23:23-25 –Numbers 10 – God prescribes the use of trumpets for Ancient Israel Spiritual Similarities?
Revelation 11:15; Zechariah 14:9 Revelation 11:15; Zechariah 14:9 –Signifies A Time of Change End Time Trumpets Revelation 19:11-21 Revelation 19:11-21 –God's Justice & Liberation
Matthew 13:18-23; 37-43 Matthew 13:18-23; 37-43 –Seeds planted –Successful Seeds – Good Ground –Endurance & Motivation –Weakness & Strengths What Does This Have To Do With Us? Mark 13:13 Mark 13:13 II Timothy 4:6-8 II Timothy 4:6-8 I Corinthians 15:51-52 I Corinthians 15:51-52
Stay The Course / Continue The Fight Hebrews 5:9 Hebrews 5:9 Philippians 4:7 Philippians 4:7 Philippians 3:9 Philippians 3:9 Hebrews 12:2 Hebrews 12:2 John 14:6; 6:63 John 14:6; 6:63 Galatians 5:16 Galatians 5:16
Isaiah 27:13 Isaiah 27:13 Focus On The Truth Of The Future
Final Lesson "You Push Yourself To What You Once Thought Were Your Limits, Then You Keep On Pushing – And You Never Quit"
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A lot of us in Oregon waking up to snow on the ground this morning. A couple flurries have blown through here but most of the inch or so w
Savage Farming
Located in Rogue River
Last update: February 27th, 2017 at 09:28 am
ping: http://ignoregon.com/ping/1262
10 post clicks in the past 90 days
Wild-eyed agriculture in the mighty Rogue Valley
Settling in for a lazy Sunday morning nap. Oatmeal & toast for breakfast w/ Ayurvedic Roast coffee substitute & hazelnut creamer,
Tomato plants are a couple inches tall in the sprout room and the small greenhouse is prepared to receive them tho I still have some clean-up to do in there. Gotta get the seed order out this week, it's getting late with less than a month of winter left. There's been some snow in the hills but we're short of water. Nothing
It's still above 95 out there so I've taken a little time after dinner to flop down in the dark, cool basement. The season is finally starting to shape up. All the crops are dialed in so we'll have at least a little of all of our mainline products with at least 2 plantings of each variety. A few weeks ago I was on the verge
Donate Bitcoins Setting up my accounts and stuff to accept bitcoins. If I can talk mom into it we might be accepting these at the stand this year.
Every few years I like to try a new endeavor on the farm. Last year it was beneficial herbs and teas. I even managed to get a tea Camilla which is still doing well. But last year was a pretty tough solo mission for the Guyman and I just barely managed to end up harvesting some miserly little piles and bags of leaf and flowe
Having such a great day. Started out kinda down but once the fog blew off and the sun warmed things up I really started going. Pruned a bunch on the apple trees and worked on cleaning out the pond. If the rain doesn't come too soon I might just get it lined in time to have some water put away for the dry part of spring. Hop
We've had a bit over a week of hard frost now. Great for killing garden insects but not great for outdoor activity. Our highest daytime temps have been around 36°F. Low nighttime temps have been 20-26. Sadly I've also hit a patch of 'writers block' with my software design work. So turning my mind
Gotta love it! Been inside so much I've finally had time to write something on here. Fall cleanup is still majorly under way. Turning to the dusty confines of the basement and the winter greenhouse for places to put stuff as revamping the house for Xmas continues. Will post some pics when we're done decorating
teetering on the top of the orchard ladder as the last rays of twilight silhouette branches of the yellow delicious apple tree. Picking apples by feel from the spindly, gnarly, gnobby branches. Yes, autumn is upon us. We'll be out of sweet corn for about a week, until the weekend or
We'll be laboring on this fine Labor Day.Corn, melon, tomatoes, squash, cukes, grapes, apples, plums, peaches, potatoes, onions and maybe even some green beans in stock today.I should be out picking corn already but the puppy sleeping on my lap is slowing me down.Y'all take care and have
My poor, sad, ol' blog has all but withered under Ra's Blazing Eye. Like one of my pumpkins being sucked dry by Coreidae. Well, your loss has been the cantaloupe's gain. We've begun to harvest some really great melons and this evening I [fina
My mom's 75th birthday is today and she'll be celebrating it in Kansas with her brothers and sister. Hope you have a super great time, Mom. You deserve it.
A movement is afoot to return control to the American people.
2nd planting of corn put in today. Boy was it hot! Being a miser with an inflatable swimming pool (thanks Todd & Robin!) full of water for my little lettuce and cabbage plants. I sure hope I don't use it all up before the polywogs get their legs. The big greenhouse has some great looking bean, tomato, cuke, squash, cant
what a delightful morning. Rotten night's sleep but a delightful morning. Sparky's asleep in my lap, warm cup of tea at my elbow. I can hear mom snoring and a few roosters still crowing. There's some lovely sunshine out there but even though I've got so much
Just filled the bird feeders and we have quite a flock in the yard.The greenhouse is filling up quickly with lots of little plants. Hundreds of tomatoes already putting on dark green growth and a big flush of new herbs and interesting flowers. Still waiting on a bundle of new plants to come in; they won't ship u
Rototilled our 1st two late winter/early spring garden plots this afternoon. Hoozah! Really nice to get the tractor out under the open sky and a bright yellow sun. Mom and I also managed a supply run to Medford this morning. Lunch at Tintin buffet. Just all around a great day. All is lined up to start planting lettuce,
25°F out there this morning. 42 in the greenhouse with 2 heaters running. Have reached about 1000 plants in there, another 400+ seeded in and kept warm in the sprouting room downstairs. I'm planning on trying to inflate the big greenhouse in the next 10 days, start getting it ready for more transplants plus early tomatoes,
Well, my cold decided to hang around some more & I didn't get the floating row cover down, darn it. Did manage a few baby steps on my job scheduling app though, that was nice. Hope you had a good Tuesday.
I've been having a challenging morning but making a little progress despite the struggle. Alas not on the greenhouse, that'll wait until this afternoon. But cleanup is going well now that equipment is cooperating. A tiny bit of sun is showing through the winter haze.
Sending us all a fine & fortuitous 2012.
My friend Terrie's sister lost their home & possessions in a house fire Christmas evening. We're all pulling together trying to help them out, if you'd like to participate in the helping, here's a place for coordinating contributio
Got the 1st leg and rafter of the small greenhouse put up on the back of our house yesterday. 9 more to go plus 2 pieces of polyethylene to top it and 2 ends to cover plus a smattering of slats, stakes and gussets. Tomatoes are growing great in the basement along with some super happy looking cukes and zukes so the greenhou
At 3:45pm today our father Johnny Giesbrecht at last set down the burdens of this world and went on to that great adventure which awaits us all. He was surrounded by his loving wife and children and was in no pain. We're all grieving here but you needed to know Johnny to understand why that grief comes with a silver lining.
another foggy Oregon morning. Aunt Anna & I are enjoying a nice pizza breakfast with hot tea.Uncle Leo, aunt Margret & uncle Ben left a little early yesterday, uncle Ben wasn't feeling good so they made sure he had plenty of time to rest at the hotel before their flight left this morning.Dad


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This is the full research report for 18.104.22.168, which is an IP address.
Administered by ARIN
Windstream Communications Inc
4001 Rodney Parham Rd
Little Rock, AR 72212
Windstream Abuse
Telephone: 18882923827
McGuire, William Windstream Communications Inc Grady, Bill
Telephone: 18882923827 18882923827 18664455
220.127.116.11 is the IP address you have a ran a report for on April, 30, 2017.
If you meant to use another IP other than 18.104.22.168, then enter above and try again.
It is 3:49 AM CEST when you ran this report for 18.104.22.168 here on our website, IP-Adress.com. When it comes to 188.8.131.52, you can trust that if we have IP Whois information available for it, we will display it further below to assist in your research of this IP address. Feel free to run another search for 220.127.116.11 or a different search.
Timestamp Confirmation:
The IP Whois report for 126.96.36.199 was ran at 3:49 AM CEST on April 30, 2017 and the information is provided below if available.
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|Hello guest sign up now!
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My IP is: 126.96.36.199


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Last night, Conan O'Brien stopped by the Daily Show, and showed off some segments and stories from his upcoming Conan in Cuba special. The comedian ventured far from his Burbank studio to film the first US program there in 50 years, and exercised the friendlier US-Cuba relations by rolling cigars with some locals. If we need a new ambassador to Cuba, Conan is certainly perfect for the job – he would also make a great travel show host.
Look how well he fits into Havana:


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Using this ISP site, locating a quality area code 817 Texas Internet service provider is a breeze. Compare popular Internet access services in Texas area code 817 and choose the TX ISP that is right for you. This comparison of the prices, tech support, customer ratings and important features of leading internet services in TX makes it simple to find the right Texas ISP.
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The following chart compares important features of texas internet access providers that have access numbers for area code 817. Click on the links for more information or to join the ISP.
†Juno Limited Time Offer: First 12 months for $6.95/month.
Cost is the per month price of the Internet service provider. In the High Speed field, we display the additional price for accelerated internet service, if it is available. Phone Support lists the availablity and cost of telephone technical support. Web Space shows the amount of webspace included with an dial up account, and Emails is how many email accounts are provided. In the Vote colum, you can click on the appropriate face to vote on whether you like or don't like each ISP. The Rating column shows the results of user voting showing the percentage of dial up subscribers that like the ISP. Use the link in the GO field to visit any texas dial up provider.
It is your exclusive responsibility to select an internet provider and access number that is in your free calling area. A listing of your city on this page doesn't guarantee the access number is a local call for your phone company.
ArcZip has Texas area code 817 access numbers in Cleburne, Dallas, Fort Worth and Granbury. Area code 817 ISP service numbers from ArcZip are also available for Reno and Weatherford.
Juno has Texas area code 817 dialup connections in Fort Worth, Arlington, Cleburne and Dallas. Atlas, Denton, Euless, Glendale, Granbury, Irving and Kennedale are different towns where Juno provides dialup access in Texas. Area code 817 internet service numbers from Juno are also available for Lake Worth, North Richland Hills, Reno and Weatherford.
NetZero has Texas area code 817 access numbers in Fort Worth, Arlington, Cleburne and Dallas. Atlas, Denton, Euless, Glendale, Granbury and Irving are different places where they provide dialup access in Texas. Area code 817 ISP access service numbers from NetZero are also available for Kennedale, Lake Worth, North Richland Hills, Reno and Weatherford.
It's your sole responsibility to select an Internet service provider and access number that's in your free calling area. Internet providers and phone numbers change often and our information can become outdated. It is your responsibility to verify all information directly before you subscribe to an ISP.
More Texas Internet access:
On EZ ISP, our internet access comparison service makes it a no-brainer to locate ISPs in Texas like in Fort Worth, Arlington, Dallas, Glendale and Frisco. We compile the locations around the USA and Canada that correspond to the dial up access numbers of each company in our ISP data base, so that you can find the internet providers with service in your location, including area code 817 and throughout Texas. In addition, we compare the important characteristics of each Texas ISP so that you can find the most favorable combination of price, customer support and features for your desires.


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Napa Valley Expo Tickets
If you have found our site, you have found an exciting way to enjoy all the events you have been waiting to see without paying hefty prices. At our site, we make do without conventional marketing, thus running the risk of being inaccessible to potential customers. But cutting down on advertising is precisely what helps us to offer the cheapest tickets for Napa Valley Expo and other exciting events. You can now enjoy Napa Valley Expo and other popular shows and events even with a tight budget! Its the word-of-mouth advertizing that keeps us going, so do tell your friends about us! No more delaying the excitement!
Latest Events
Date & Time
- BottleRock Music Festival - Saturday, Napa Valley Expo tickets for 05/27 11:30 AM at Napa Valley Expo ,Napa ,CA
- Sat May 27 2017
- BottleRock Music Festival - Friday, Napa Valley Expo tickets for 05/26 11:30 AM at Napa Valley Expo ,Napa ,CA
- Fri May 26 2017


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Meet Hines Ward — Rachael vs. Guy: Celebrity Cook-Offby Joseph Erdos in Shows, December 30th, 2012
FN Dish is counting down to the season 2 premiere of Rachael vs. Guy: Celebrity Cook-Off by introducing a new celebrity contestant every day. The competition tests the celebrities to see who has the culinary chops to win the title of champion and guarantees a $50,000 donation to the winner's charity of choice. Watch the premiere on Sunday, January 6, at 9pm/8c and keep coming back to FN Dish for exclusive interviews and behind-the-scenes previews.
Former NFL player Hines Ward is a two-time Super Bowl champion, MVP of Super Bowl XL and four-time Pro Bowler. But this athlete isn't embarrassed to get in the kitchen; in fact at 6 years old, he was a fan of the Easy-Bake Oven. Get to know Hines better from his Q&A with FN Dish.
The two words that best describe your cooking style are…
Hines Ward: Spontaneous and fun
What's your earliest food memory?
HW: At 6 years old I remember that little toy cooking set, the Easy-Bake Oven.
What's the best meal you ever ate?
HW: My mom's Korean barbecue ribs
Going into Rachael vs. Guy, who did you think was going to be your biggest competition?
HW: Dean McDermott — he went to culinary school
Favorite pizza topping?
HW: Pepperoni
Who is your favorite food TV personality, past or present?
HW: Paula Deen
What food will we never catch you eating?
HW: Liver
What's your signature party dish?
HW: My Asian persuasion wings
Sweet tooth, salt tooth or both?
HW: Both
What kitchen tool can't you live without?
HW: Tongs
What's the most surprising thing we'd find in your fridge?
HW: Chocolate milk
What music do you like to listen to in the kitchen?
Meet the rest of the celebrities:
Cornelia Guest
Gilbert Gottfried
Dean McDermott
Kathy Najimy
Carnie Wilson
Johnny Weir
Similar Posts
What to Watch: Wine-Infused Recipes and a Tropical Ingredient Showdown on Iron Chef GauntletGet all the details on the upcoming premieres this weekend on Food Network....
- Chopped Star Power: Exclusive Interview with the Part 4, Screen Stars Winner
- Exclusive: Chatting with the First Iron Chef Gauntlet Challenger to Go Home
- What to Watch: Lots of Chicken on The Kitchen and the Premieres of Iron Chef Gauntlet and Iron Chef Eats
- Chatting with Iron Chef Gauntlet Judges Geoffrey Zakarian and Donatella Arpaia


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Paul, Billups, Griffin back vs. Heat
Associated Press | Last updated February 08, 2013
The Los Angeles Clippers are getting healthier. The Miami Heat are fighting the flu. Chauncey Billups, Chris Paul and Blake Griffin returned to the Clippers' lineup on Friday night, when the Pacific Division leaders visited the reigning NBA champion Heat - who were without Ray Allen and Chris Bosh, both sidelined by an illness that has been going around the team. Miami did have Dwyane Wade in the lineup, after he wasn't feeling well earlier Friday and missed the team's morning shootaround. ''We're trying to get our team back together,'' Clippers coach Vinny Del Negro said. ''Right now it's just about trying to manage through the injuries, trying to see if we can become whole as we move through this long road trip.'' Del Negro said he would manage the minutes of those players who are coming back from injuries, a list that also includes Jamal Crawford, who has been bothered by a sore right shoulder. Billups has appeared in only three games this season and has most recently been bothered by left foot tendinitis. Paul missed the Clippers' last nine games before Friday with a bruised right kneecap, and Griffin sat out two games with a strained left hamstring. For as strong as the Clippers have been at times this season - including a 17-game winning streak from Nov. 28 through Dec. 30 - Thursday marked the first time Del Negro had all 15 players available for practice. Even that was limited, since Griffin's leg kept him from participating in any full-court portion of that workout. ''We've got to get our rotations down, figure out who's healthy and what we can go to at certain times,'' Del Negro said. ''And that's going to take a little more concentration on our guys' part and understanding what we can do out there on a consistent basis.'' To say the Clippers were thrilled to have their full complement of players back was a bit of an understatement. ''The urgency and also the basketball IQ and disposition, everything, just went to a whole `nother level,'' Clippers forward Caron Butler said. For the Heat, the flu has been a bit of an issue of late. Heat President Pat Riley missed the team's recent visit to the White House because of the illness, and Bosh has been fighting it for much of this week. Allen was not at the shootaround, and it was clear then that he wouldn't be available for the Clippers game. Miami next plays on Sunday, home again against the Los Angeles Lakers. ''I feel different each day,'' said Heat forward LeBron James, who has battled congestion this week. ''Just try to get as much Vitamin C, just try to take your vitamins, just try to stay on course and not let it affect you.'' Heat coach Erik Spoelstra said he wasn't caught off guard by the Clippers having their full roster back, and that Miami prepared for that likelihood. There was one roster move the Heat made on Friday that wasn't illness-related: They signed forward-center Chris Andersen for the remainder of the season, as has been expected since they brought him into the organization three weeks ago.
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The late summer border is a riot of colour, but I think echinacea with their vibrant pink daisy-like flowers and orange centres are stars of the show! This is a loose, painterly impression of those flowers on a hot summers' day.Watercolour paper has two usable sides, and occasionally I use both if an experiment doesn't work. This painting has some marks on the reverse but this in no way affects the artwork.
Artist's quality watercolour paints on 300gsm Fabriano Artistico watercolour paper
Painting by Ruth Harris
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Myanmar Will not Meet Annual Fisheries Export Target08 March 2013
MYANMAR - Myanmar will not meet its marine-products export target of US$700 million for this fiscal year, the fish and fisheries products federation said, pointing to official figures for the first 11 months of the fiscal year.
The figures from the Fishery Department show that export of marine products totaled $581.819 million from the beginning of the fiscal year last April to 24 February this year, reports ElevenMyanmar.
Exports of crab and eel have exceeded their targets, but exports of freshwater shrimp and other fish have fallen short of target, official figures show.
TheFishSite News Desk
Markets and Economics, Eels, Government and Regulatory, General, Aquaculture, Crabs and Lobsters, Sustainable Fishing


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Chris Larson 10/14..."I just thought I'd post these photos as some who trawl eBay will have seen them but others haven't.
The story started with Peter Tristram & I importing some plants of Guatemalan origin out of Europe. We both got a couple of T. capitata var guzmanoides which were a nice darker clone with scarlet bracts – and definitely not var guzmanoides. These flowered at a smaller size, at least mine did, at around 12" tall. It also self set seed.
Then I got offered some more expensive Guatemalan plants (than our usual lines) as a one off – which included this var guzmanoides again. I only got a few. Some flowered at around 45cm tall with scarlet bracts – and are just starting to pup. Monster capitatas – as those that have seen them will attest. A few nutters have them now. I thought I'd better put this info out as these plants will be appearing around.
I'm still not sure whether to register it as T. capitata 'Scarlet' as I'm not sure that the 2 clones I have are not the same or what will happen with the pups."
Derek Butcher 11/14...."The only ones really interested in blatant wrong names seems to be we Antipodeans! Bromeliads in Australia has the problem partly solved because the right detail are under T. lautneri. Feldhoff started off this misnaming. The use of Scarlet is a nurseryman's solution but is frowned upon by Registrars. Why not call this 'Feldhoff'? It identifies the source AND that it is different."


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Thanks for helping!
Stunningly well preserved Bronze Age well north of Olbia center. You need to go via the zone industriale to get access and parking as the old sign by the national road is...
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Stunningly well preserved Bronze Age well north of Olbia center. You need to go via the zone industriale to get access and parking as the old sign by the national road is completely closed off. Impressive construction with clear waters filling the well.
A great place to get some insight in religious customs way back when... Water has always been important, source of life and here you can actually feel just that, you can only imagine how thousands of years ago people gathered at this spot. I could not believe how much is actually preserved. Loved visiting this well!
A remarkable site, not only for its archaeological significance, but for the palpable air of otherness within it.
I was not expecting it to be so well preserved and set in a beautiful natural place filled with native plants (which are labelled - a great touch), especially considering its proximity to an industrial estate. The myrtle was in full bloom,...
I think the signposting says it all really! Make the place difficult to find because at least you will have spent as many minutes finding the place as you are likely to spend actually at this place.
In fairness the Sards have tried to make the actual site a bit more interesting once you arrive, by placing useful plaques and...
First off, this place is slightly tricky to find - the key is to take the small road that is immediately behind the supermarket, which can be difficult to access when you come off the crazy Italian roundabout.
Anyway, we arrived expecting to just spend a few minutes walking around, but for reasons that were never fully explained there was...
It is a bit difficult to find this site, even with a GPS. So follow the street that goes to the mall. I was lucky to be there and be guided by three very charming and adorable high school students trying to practice their English. The trip was worth only because of them! If you don't have a guide, read...
To find the Pozzo Sacro is not so easy as the road signs are difficult to see. Easiest is to go by car in the direction to Pittulongo, and turn right when the Pozzo Sacro hotel appears on left side of the road. Pass the entrance to the supermarket, and find a small signposted road to the left. This site...
It is a very interesting place although there is no one there to offer answers for questions and little literature to read on the place
pozzo sacro sa testa it is the most important ritual space in Sardinia. not only the native of the island have worshiped their gods there, but also the conqueror of the island and even at last the romans. a lot of stories are told about the place, but no one knows exactly which of the many handed down legends are...


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I have to start by saying that I have purchased several wool rugs from Overstock and have never been disappointed with the quality. I am a bargain shopper and have yet to find anyone that can beat O's quality and prices on rugs. The downfall to shopping for a rug online is that the descriptions and pictures are not always true to the actual item. This rug is beautiful in design and quality; however the colors are different than what you see in the picture. Hopefully I can save other buyers the hassle of rolling the dice on whether this rug will match their color scheme. First, the red on this rug is a blood red and is not as bright as you see in the pic. It's not maroon or burgandy, it's a deep blood red. The border is definitely black but what appear to be gold accents, are actually more of a dull tan leaning toward a muddy green. There are no real gold tones in this rug. The main colors on this rug are sage and red. There is a LOT of sage, which unfortunately was not what I expected. Bottom line, if you're looking for a rug with deep red and sage that has some black in it, this is the rug for you! A very thick rug with no shedding and crisp detailing. Looks a lot more expensive than the $**** you're paying for it. Worth your money, especially if these are the colors that you need. I only gave it 4 out of 5 stars because the description and pictures are not true to the actual item. I am very happy with the quality. I'm not returning it because for the money, this is a great deal even if the colors are a little off from what I was expecting.Read More
The rug is absolutely gorgeous. I bought it for my breakfast area. However, it is now placed in my foyer. The colors are brillant. First, I thought the gold color was deceiving. However, when I moved it to a different lighting, it is a true gold. I enjoy standing on the rug with my bare feet. It is quite thick. I read the reviews about packaging. Apparently, Overstock took the comments into consideration. My rug was rolled into a thick pull on bag. I had no damage. If the size is correct and you are looking for a red/gold/black wool rug, this one is for you.Read More
This was my first purchase on overstock.com. I had been looking for nice area rugs for my hardwood floors. I couldn't find any wool rugs in this size, thickness, and quality for under $650. The rug is plush, thick, and soft to the touch. The red in this rug is a true dark red (not orangy like the picture looks). I have received many compliments and when people hear what I paid for the rug they are very surprised.Read More
I was trying to find a rug with reds or burgandies. The picture looked like a perfect match. It arrived very quickly, packaged perfectly. As I opened the rug up..I was very impressed with the quality. It feels very thick when you walk on it. My only disappointment was the color was more grape than it appeared in the picture. It didn't go in the room I had intended, but I liked it so much I found another place for it. And now it looks perfect!Read More
purchased this rug to "match" an existing round we have in the same room, as if that was possible. So pleased to say this exceeded our expectations and matched perfectly with the burgendy and black rug we had. the design is pleasing and rich looking. you can't go wrong with this purchase for a cozy, rich room.Read More
Great deal...good colors, great qualityRead More
The rug sets on a hardwood floor in the entry of our house; first thing you see when you open the door; great eye catcher; love it. Color is excellent and price is better than any one on the internet sales. great rug, great price; you will like it.Read More
I am very satisfied with this rug - it is better quality than I expected.Read More
I have this as my living room rug and I still love it now as much as when I first purchased it.Read More
Love the rug but it is smaller than 5 x 8. More like 4.8 x 8. You would not think 2 inches is a big deal but I noticed it right away. Other than the size disappointment, the rug is well made, plush and worth the money.Read More
I have a large foyer and wanted a larger rug. This one did the trick. I wish I'd bought one of these for every room in my house! The color? Gorgeous and rich although I will say the description reads "burgundy" but I find it to be a deep rich shade of true red and not what IMO is "burgundy" which would have more of a purplish lean. This is just like the picture - I'm glad I used that as a guide and not the description. The color has held fast and true with no fading, and I've had it a year and a half. I also had a dog since passed with bowel cancer and can't tell you the gross things that have been deposited on this carpet- and have cleaned up with a regular household carpet cleaner, with no damage to the rug, no permanent stains, etc. This rug is THICK, woven so tightly it's a joy on bare feet. It has held up like a champ to heavy foot traffic not only from humans but from three giant dogs with big feet and sharp nails. Nary a pull on it. I have to say I am truly amazed. I can't recall the last time I spent so little on a rug and had it hold up like this. I actually came back to buy more and they're out of stock. I want one for my informal dining area, one for my morning room, one for my bedroom and anywhere else I have hard surface flooring. It's no exaggeration to say I'd like to carpet my whole house with this type of rug. You will NOT be disappointed.Read More
We are very pleased with this rug: colors are vibrant and true and it is very plush.Read More
Absolutely thrilled with this purchase. Extremely high quality, and visually appealing. A great carpet to walk on in your bare feet.Read More
This rug is very well made. There is a brighter green in it that doesn't show up in the picture. The green goes well in the rug but take note - this rug is NOT 5x8. It is about 3 to 4 inches shorter in width and length. Because of this, it did not fit under my kitchen table. The rug also arrived a little damp and musty smelling. It seemed like it was sitting in a warehouse for a long time. A much better choice is the Heritage Kashan red and black rug. It is similar but much more elegant.Read More
Great rug for a great price! The color is very different from the color shown in the picture...but still looks great and is great quality for the price.Read More
fast shipping, great quality, good color, much more than expected, love this carpet!!Read More
This is my third Agra Wool rug purchase . I am thrilled with the look, the price & of course the cost of shipping. Keep up the good work overstock!Read More
I bought two of these rugs. They are SO THICK and cushy it's hard to believe the price. The red is a darker red but in daylight in my house it IS red and not merlot etc. the workmanship is EXCELLENT I wish I had other places to put more of these rugs.Read More
This rug has rich colors and is very thick. No shedding. It exceeded my expectations. If anything I would have gotten it a little bigger.Read More
i love the rug it match my one in the dinning and it was purchased 3 yrs ago however this rug seem to have a few snags in the tuft put for the price it is greatRead More
Hand-tufted Agra Burgundy and Black Indian Wool Rug (5' x 8')
Today: $157.99


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on Feb 08, 2011 @ 10:10 am
Let's face it, the Razzies are probably more entertaining to watch than most awards shows. There is a lengthy list of nominees some of which include Sarah J Parker for worst actress in Sex and The City 2, Cher for worst supporting actress in Burlesque, and Twilight's hunks for worst actors. Check out full list here. at CTV.com
Ali de Bold
|Funny on Feb 08, 2011 @ 08:39 pm
I think the whole concept of Razzies is hilarious, though it must be embarrassing to be nominated!
|This is great but.. on Feb 11, 2011 @ 02:02 pm
...I liked Burlesque, and I liked Cher.


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Enter keywords or a search phrase below:
I haven't been building any models for a long time due to my health but i can now I have bought me a mini airbrush & compressor kit & 3 Master Air brushes i know that these are more than likely junk to most of you modlers but i have to buy what i can afford I bought a 15 Camel Hair paint brush set i bought 30 bottles of Testors Acrylic model paint New I am very excited to be a member
Welcome to the Forums Trapper! Glad to have you aboard!
You've come to the right place. The members are very knowledgeable and ready to help out with any questions or problems that you might have. We've all started somewhere sometime. The object here is to relax and enjoy the hobby. We're here to help you do this. Don't be afraid to ask questions.
Sooooooo, sit back, have a few sips of your favorite brew whether it be , , , or my favorite and build away.
Main WIP: Rebuild of Monogram 1/8 "Big Deuce" with 1/8 Pocher V-12 in rear - 10%
On the Bench: Revell 1/48 Ju 52/3m - 50%; Revell 1/96 USS Kearsarge - 20%
I keep hitting "escape", but I'm still here.
Welcome and enjoy!
Rich - "And when the Band you're in starts playing different tunes, I'll see you on the Dark Side of the Moon" - Pink Floyd
We all start somewhere, with practice and patience you may become the best "crappy airbush" user around. Do not sell yourself short and never be afraid to ask for help. WELCOME ABOARD
we're modelers it's what we do
Welcome aboard. Don't be afraid to ask for help. Let us see how you are doing when you get a model in process. I look forward to seeing what you come up with.
Our community is FREE to join. To participate you must either login or register for an account.


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Portuguese translation of 'reiterate'
Word Frequency
reiterate [riːˈɪtəreɪt]
transitive verb
Copyright © 2014 by HarperCollins Publishers. All rights reserved.
Example Sentences Including 'reiterate'
But I do reiterate , anyone caught acting in breach of a prohibition order is liable to two years ' imprisonment.TEN STEPS TO HAPPINESS (2003)
I reiterate , sirrah...' Alpiew had no desire for a kiss from Mr Pepys.THE RIVAL QUEENS: A Countess Ashby de la Zouche Mystery (2002)
The lawyer, however, could only reiterate what he had said before.Unto The Grave
Trends of 'reiterate'
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'reiterate' in Other Languages
Translation of reiterate from the Collins English to Portuguese Dictionary
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Simeonie Keenainak
From Wikipedia, the free encyclopedia
Simeonie Keenainak is an Inuit accordionist and retired RCMP officer from Pangnirtung, Nunavut, Canada. He is also a photographer and hunter. He has performed at the Pangnirtung Music Festival and was featured in regional and national media for his musicianship and cultural community efforts.
Simeonie and Daisy Keenainak have been married since 1967.
External links[edit]
- CBC Radio One Hotsheet (21 July 2004, item 5. Outfront)
- Canadian Folk Music Bulletin: Inuit Accordion Music-A Better Kept Secret (PDF format, March–June 2000, by Jim Hiscott, accessed 20 May 2006)
- Nunatsiaq News: "Selected music from Pang festival now on CD"
- Legislative Assembly of Nunavut: comments by Hon. Jack Anawak (PDF format, 1 November 2002, p1507)
|This article about a Canadian musician is a stub. You can help Wikipedia by expanding it.


text: The owner of the house met us on arrival and guided us to the house. He also showed us all the facilities and around the garden. The house is very beautiful and suitable for a large family. The bedrooms are excellent, plenty of room and nice furniture. The garden is beautiful and well taken care of. The swimming pool is fenced off which is very good when travelling with young children.The caretaker of the house and garden is very helpful and nice.The house is a few kilometers away from the nearest town so all service has to be reached by car. Over all an excellent house for large groups or families, a bit remote in beautiful surrounding.


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Foreign Affairs
Love in the Time of Bollywood
Foreign Affairs
November 14, 2013. A couple stands near the seafront during heavy rains in India's financial capital Mumbai June 7, 2008. (Punit Paranjpe / Courtesy Reuters). At nine every morning, Sana dons her burqa and rides pillion on her father's scooter. He …


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Treatment Guide/ECS Consultant -Franklin, TN
Entry Level Qualifications
HSD/GED required; college helpful. Knowledge of chemical dependency is desired. Knowledge of and experience in marketing desired. A knowledge/skill of computer data entry is strongly preferred. Must be able to interact with the professional community. Must have reliable transportation. Must be able to do 24 hour a day on call schedule. Must be self-motivated and able to work under minimal supervision.
Interested applicants please email resumes to: firstname.lastname@example.com or fax resumes attn: Bev Fulkerson to: 615-595-8842.
Learn more about the location: Franklin, TN