Structure and Uses of Ibuprofen

Structure and Uses of Ibuprofen Abstract The Controlled-release dosage forms are formulated to release the drugs active ingredient gradually and predictably over an extended period of time that is something like 12 to 24 hour period. â€Å"These formulations potentially provide for greater effectiveness in the treatment of chronic conditions through more consistent delivery of the medication; reduced side effects; greater convenience; and higher levels of patient compliance due to a simplified dosage schedule, compared with those of immediate-release drugs†. Ibuprofen is a colourless, crystalline solid which is having a low soluble limits in water but it is having a better solublity in most organic solvents. â€Å"The main aim of this work is control the release of drug by encapsulating it in to coating materials like fattyacids (palmiticacid and pluronic F-127). Encapsulating of ibuprofen by using freeze drying technique in this technique Ibuprofen is encapsulated in to the fattyacid and pluronic (F127), these coating materials have the property of controlling the release of drug when the coated drug is entered in to the body the coating materials which surrounded to the drug is control the release of drug†. The release of encapsulated ibuprofen is determined by Flow through dissolution and UV- visible spectroscopy. INTRODUCTION 1. IBUPROFEN Ibuprofen is a colourless, crystalline solid which is having a very very low solubility limits I case of water but it is having comparabelly better soluble limits in case of organic solvents. The synthesis of ibuprofen was originally reported in 1964 from Ï -isobutyl- lacetophen but the drug was not marketed in the United States until 1974 despite the fact that it had been available for several years in Europe. â€Å"It was the indomethacin and was immediately accepted in therapy. Its success was a factor in the introduction of many new agents in the 1970s. Ibuprofen was the first aryl propionic acid derivative to be marketed in the United States†. This chemical class currently comprises of the largest group of NSAIDs under investigation with as many as 25 derivatives in various stages of development. â€Å"It recently became the first prescription NSAIA to become available as an over the counter analgesic in almost 30 years and is avialble under a number of trade names, It is also sometimes known as: Advil, Anadin Ibuprofen, Arthrofen, Brufen, Retard, Cuprofen, Fenbid; Galprofen, Hedex Ibuprofen, Ibufem; Librofem; Mandafen; Manorfen; Migrafen; Motrin; Nurofen; Obifen; Relcofen perhaps being among the more widely used. The continuing popularity of ibuprofen is evidenced by the appearance 200 prescription drugs in the United States†. IUPAC name : 2-[4-(2-methylpropyl) phenyl] propanoacid, Formula : C13H18O2, Molecular mass : 206.28, Melting point : 76  °C (1. 69  °F) Bioavailability : 49-73, Protein binding : 99%, Metabolism : Hepatic, Half life : 1.8-2 hours, Excretion : Renal. 1.1 Structure of Ibuprofen Structure of IBUPROFEN Ibuprofen is a white powder belonging to the propionic acid derivatives, with a melting point of 74 77 ° C. It is only slightly soluble in water but readily soluble in organic solvents such as ethanol. It is a chiral compound; racemic Ibuprofen is usually used, although only one form is active medicinally. â€Å"Ibuprofen is made up of covalently-bonded carbon, hydrogen, and oxygen atoms. 2 CH3 molecules are single-bonded to a CH molecule The CH molecule is bonded to a carbon atom that forms a 6-sided ring of carbon atoms†. Another CH molecule is single-bonded to a carbon atom on the other side of the ring. Inside the ring there are 3 double bonds between carbon atoms. Then another CH3 molecule and a COOH molecule are both single bonded to the CH molecule on the right. Because it is nonsteroidal, it is widely used as it does not upset the hormonal balance in the body. Its anti-inflammatory, analgesic (pain relieving) and antipyretic (fever reducing) actions are co moderate pain such as headache, toothache, and migraine as well as symptoms of fever. 1.2 Stereochemistry Ibuprofen contains a chiral carbon in the ∞ position of the propionate moiety. As such, there are two possible enantiomers of ibuprofen, with the potential for different biological effects and metabolism for each enantiomer. Indeed it was found that (S)(+)- ibuprofen (dexibuprofen) was the active form both in vitro and in vivo, because of this reason the ibuprofen is marketed as a single enantiomer as occurs with naproxen and other NSAIDs. And the in vivo experiments revealed the existence of an Isomerase (2-arylpropionylco-A epimerase) which converted (R) -ibuprofen to the active (S)-enantiomer .Most of the ibuprofen formulations are marketed as racemic mixtures. Racemic ibuprofen is an important NSAID used in the treatment of pain and inflammation in a variety of musculoskeletal rheumatic disorders. 1.3 Synthesis â€Å"There have been many commercial and laboratory publications for the synthesis of Ibuprofen. Two of the most popular ways to obtain Ibuprofen are the Boot process and the Hoechst process. The Boot process is an older commercial process developed by the Boot Pure Drug Company, and the Hoechst process is a newer process developed by the Hoechst Company. Most of these routes to Ibuprofen begin with isobutyl benzene and use Friedel-Crafts acylation. The Boot process requires six steps, while the Hoechst process, with the assistance of catalysts, is completed in only three steps†. Cheminor Drugs have developed a process for an improved version of ibuprofen based on chiral synthesis. The move is significant given that pure S-Ibuprofen (the active form of ibuprofen) could near halve the regular ibuprofen dosage, besides improving the side-effect profile. However the human body can convert the inactive (R) form into the (S) form, so eventually 100% of the ibuprofen taken becomes active. The process discovered by Cheminor is therefore unlikely to have commercial significance. [6] 1.4 Mechanism of action: â€Å"Ibuprofen is an NSAID which is believed to work through inhibition of cyclooxygenase (COX), thus inhibiting prostaglandin synthesis. There are at least 2 variants of cyclooxygenase (COX-1 and COX-2). Ibuprofen inhibits both COX-1 and COX-2. It appears that its analgesic, antipyretic, and anti-inflammatory activity is achieved principally through COX-2 inhibition; whereas COX-1 inhibition is responsible for its unwanted effects on platelet aggregation and the GI mucosa†. The role of the individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of NSAIDs is uncertain and different compounds cause different degrees of analgesia and gastric damage. 1.5 Absorption and metabolism: Ibuprofen is quite rapidly absorbed when it is admistered orally we can witness the peak plasma levels are obtained withan 2hours time.† As with most of these acidic NSAIDs , ibuprofen(pka=4.43) is extensively bound to the plasma proteins(99%) and will interact with other acidic drugs which are protein bound. Metabolism occur rapidly and the drug is nearly completely excreted in the urine as UN changed drug and oxidative metabolites with in 24 hrs following administration†. Metabolism involves primarily ω-1and ω-2 oxidation of the Ï -iso butyl side chain, followed by alcohol oxidation of the primary alcohol resulting from the ω-oxidation to the corresponding carboxylic acid. All metabolites are essentially in active. When Ibuprofen id administered as the individual enantiomers, the major metabolites isolated are the (+)-isomers regardless of the configuration of the administered enantiomer.intrestingley, the (R)(-)-enantiomer is inverted to the (S)-(+)-enant iomer in vivo, accounting for the observation that the two enantiomers are bioequivalent In vivo. 1.6 Ibuprofen uses: Ibuprofen is used to relief the symptoms of a wide range of illnesses such as headaches, backache, period pain, dental pain, neuralgia, rheumatic pain, muscular pain, migraine, cold and flu symptoms and arthritis. Recently evidence has emerged suggesting that ibuprofen is effective in the treatment of Alzheimers disease. 1.7 Ibuprofen side effects Ibuprofen is regarded as the first choice drug in its class due to the low number of side effects and complications associated with it. The most frequent type of adverse reaction occurring with ibuprofen is gastrointestinal. In clinical trials, the percentage of patients reporting one or more gastrointestinal complaints ranged from 4% to 16%. Common Side Effects: stomach upset or irritation Infrequent Side Effects: nausea and/or vomiting, constipation, diarrhoea Rare Side Effects: skin irritations, drowsiness, gastrointestinal bleeding Ibuprofen has the lowest incidence of gastrointestinal adverse effects, reactions of all the non selective NSAIDS. However this only holds true in case of lower doses of ibuprofen, so over the counter preparation of ibuprofen are generally labelled to advise a maximum daily dose of 1,200 mg. 1.8 Risks involved 1.8.1 Cardiovascular Risk: Along with several other NSAIDs, ibuprofen has been implicated in elevating the risk of myocardial infarction, particularly among those chronically using high doses. 1.8.2 Risks in Pregnancy: Ibuprofen consumption should be avoided in late pregnancy due to risk of premature closure of the ducts arteries in the fetal heart. 1.8.3 Risks in Inflammatory Bowel Disease â€Å"Ibuprofen should not be used regularly in individuals with Inflammatory Bowel Diseas (IBD-Crohns Disease and Ulcerative Colitis)due to its ability to cause gastric bleeding and form ulceration in the gastric lining. Drugs such as Advil should be avoided in persons afflicted with IBD. Pain relievers such as Tylenol (containing acetaminophen) or drugs containing Codeine (which slows down bowel activity) are safer methods than Ibuprofen for pain relief in IBD†. Ibuprofen is also known to cause worsening of IBD during times of a flare-up, thus should be avoided completely. 1.8.4Drug-Drug Interactions Ibuprofen is associated with several suspected or other probable interactions that can affect the action of other drugs .Ibuprofen leads to the increased levels of lithium leading to the reduction of lithium excretion from the kidneys, and this may lead to lithium toxicity. Ibuprofen may lead to the lowering of blood pressure because prostaglandins play an important role in reducing the blood pressure. Ibuprofen is used in combination with amino glycosides for e.g.: The blood levels of gentamycin may increase presumably because the elimination of amino glycosides from the body is reduced and may lead to amino glycoside side effect. 1.9. Absorption and Metabolism Ibuprofen is rapidly absorbed on oral administration with peak plasma levels being generally attained with in 2hrs. As with most of these acidic NSAIDs , ibuprofen(pka=4.43) is extensively bound to the plasma proteins(99%) and will interact with other acidic drugs which are protein bound. Metabolism involves primarily ω-1and ω-2 oxidation of the Ï -iso butyl side chain, followed by alcohol oxidation of the primary alcohol resulting from the ω-oxidation to the corresponding carboxylic acid. All the metabolites are essentially inactive. The (R)(-)-enantiomer is inverted to the (S)-(+)-enantiomer in vivo, accounting for the observation that the two enantiomers are bioequivalent In vivo. 1.9 Mechanism of Action Ibuprofen is an NSAID which is believed to work through inhibition of cyclooxygenase (COX), thus inhibiting prostaglandin synthesis. Prostaglandins are produced in response to injury or certain diseases 2 variants of cyclooxygenase (COX-1 and COX-2). Ibuprofen inhibits both COX-1 and COX-2. It appears that its analgesic, antipyretic, and anti-inflammatory activity is achieved principally through COX-2 inhibition; whereas COX-1 inhibition is responsible for its unwanted effects on platelet aggregation and the GI mucosa. The role of the individual COX Isoforms in the Analgesic, Antiinflammatory, and the Gastric damage and affects of NSAIDs is uncertain and different degrees of Analgesia and Gastric damage occur. 1.10 Controlled Release Mechanisms Controlled release implies regulation of the delivery of a a drug by a device the control is aimed at delivering the drug at a specific rate for a definite period of time independent of the local environments. Controlled release may also incorporate methods of promote localization of drug at an active site. Site specific and targeted delivery systems are the descriptive term used to denote this type of control. The periods of delivery are much longer than in case of sustained release and may vary from days to years. Controlled release mechanism is designed to release the drug in vivo according to predictable rates that can be verified by in-vitro measurements. Controlled release technology implies a quantities understanding of the physic chemical mechanism of drug availability to the extent that the dosage form release rate can be specified. Potential development s and new approaches to oral controlled release drug delivery systems, intragastric floating tablets, Trans mucosal tablets and micro porous membrane coated tablets . An example of application to the controlled release technology to dosage form design consists of a polymer matrix in which a drug containing solution is dispersed in the form of micro cells. The barrier permeability and the drug solubility in the dispersed solution are variables that can be adjusted to provide predictable drug release rates. All pharmaceutical dosage forms should be controlled release formulations -with rate specified and bioavailability assured by the drug delivery design. There are three types of controlled release mechanisms: Ø Diffusion Ø Swelling Ø Degradation 2 .Palmitic acid Palmitic acid,CH3(CH2)14COOH or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants. As its name indicates, it is a major component of the oil from palm trees (palm oil and palm kernel oil). Palmitate is a term for the salts or esters of palmitic acid. The palmitate anion is the observed form of palmitic acid at physiological pH. CAS number 57-10-3 Molecular formula C16H32O2 Molar mass 256.42 g/mol Appearance White crystals Density 0.853 g/cm3 at 62  °C Melting point 63-64  °C Boiling point 351-352  °C[2] 215  °C at 15 mmHg Solubility in water Insoluble 2.1 Biochemistry â€Å"Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl- CoA carboxyl(ACC) which is responsible for converting acetyl-CoA to malonyl-CoA which is used to add to the growing acyl chain, thus preventing further palmitate generation. Reduction of palmitic acid yields cetyl alcohol†. 2.2 Uses Derivatives of palmitic acid were used in combination with naphtha during World War II to produce napalm (aluminum naphthenate and aluminum palmitate). [6] â€Å"The World Health Organization claims there is convincing evidence that dietary intake of palmitic acid increases risk of developing cardiovascular diseases. However, possibly less-disinterested studies have shown no ill effect, or even a favorable effect, of dietary consumption of palmitic acid on blood lipids and cardiovascular disease, so that the WHO finding may be deemed controversial.[8] However, another study showed that palmitic acid has no hypercholesterolaemic effect if intake of linoleic acid is greater than 4.5% of energy. On the other hand, it was shown that, if the diet contains trans fatty acids, the health effects are negative, causing an LDL cholesterol increase and HDL cholesterol decrease†. â€Å"Recently, a long-acting anti-psychotic medication, paliperidone palmitate (marketed as INVEGA Sustenna), used in the treatment of schizophrenia, has been synthesized using the oily palmitate ester as a long-acting release carrier medium when injected intramuscularly. The underlying method of drug delivery is similar to that used with decanoic acid to deliver long-acting depot medication, in particular, neuroleptics such as haloperidol decanoate†. 3 .Pluronic F-127 Pluronic F127 is a difunctional block copolymer surfactant terminating in primary hydroxyl groups. A non-ionic surfactant that is 100% active and relatively nontoxic. 3.1 Specifications Cloud point (10% aqueous)†¦.. >100 °C Color, APHA †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦ 120 max. Water, weight %†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦. Cast Solid-0.4 max. Prill/Micropastille-0.75 max. pH (2.5% aqueous)†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦ 6.0 7.0 3.2 Typical physical properties Form†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. Cast solid /Prill /Micropastille Average molecular weight†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.†¦ 12600 Specific gravity, 77 °/25 °C†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. 1.05 Viscosity, cps at 77 °C †¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. 3100 Melt Point†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦. 56 °C Cloud point (1% aqueous)†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.†¦ >100 °C Foam height (Ross Miles, 0.1% aqueous at 50 °C)†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. 40 mm Surface tension (0.1% aqueous)†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦.. 41 dynes/cm at25 °C HLB†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦ 18 − 23 Solubility in water at 25 °C†¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦Ã¢â‚¬ ¦. >10% Wetting, Draves Sink Time (3-gm hook, 0.1% aqueous at 25 °C)†¦.. >360 seconds â€Å"Pluronicf-127 is polymer with an additional property in aqueous solution which will covert from its liquid state to that of a non fluid hydrogel, which is a main characteristic of the protein drug delivery system†.Pluronic-f127 is also considered as an Thermo Reversible Gelatine of the co-polymer f127 whose generic name is 407 in water makes it an unique candidate for Microencapsulaton application â€Å"Pluronic-f127 is a surfactant molecule with highly beneficial characteristics that makes it a strong candidate for protein drug delivery system. Its interaction with the polypeptides is most likely of minimisation of potential energy by mutual exclusion of hydrophobic residues from the aqueous medium as was predicted by computer probing and verified by fluorescent probing†. 4. Microencapsulation This is a process by which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. These micro-capsules have a number of benefits such as converting liquids to solids, separating reactive compounds, providing environmental protection, improved material handling properties. Active materials are then encapsulated in micron-sized capsules of barrier polymers (gelatin, plastic, wax, ). â€Å"The reasons for micro encapsulation are countless. In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen, retarding evaporation of a volatile core, improving the handling properties of a sticky material, or isolating a reactive core from chemical attack. In other cases, the objective is not to isolate the core completely but to control the rate at which it leaves the microcapsule, as in the controlled release of drugs or pesticides†. The problem may be as simple as masking the taste or odour of the core, or as complex as increasing the selectivity of an adsorption or extraction. 4.1 Micro encapsulation techniques: *Physical methods of encapsulation > Rotary disk atomization > Fluid bed coating > Stationary nozzle co extrusion > Centrifugal head co extrusion > Submerged nozzle co extrusion > Spray drying > Pan coating * Chemical methods of encapsulation > Phase separation > Solvent evaporation > Solvent extraction > Interfacial polymerization > Simple and complex coacervation > In-situ polymerization > Liposome technology * Shell materials used for en capsulation > Proteins > Polysaccharides > Starches > waxes > Fats > Natural and synthetic polymers > Resins 4.2 Chemicals used in this experiment: Drug: IBUPROFEN Coating polymer: pvp and pluronic (f77) Phosphate buffer (7.4) Composition of phosphate buffer Ø Potassium chloride Ø Sodium chloride Ø Potassium di hydro ortho phosphate Sodium di hydro ortho phosphate 6. Freeze Drying: Freeze-drying (also known as lyophilisation or cry desiccation) is a dehydration process typically used to preserve a perishable material or make the material more convenient for transport. Freeze-drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to gas. There are several stages involved in the freeze drying process 6.1 Freezing stage: â€Å" The freezing process consists of freezing the material. In a lab, this is often done by placing the material in a freeze-drying flask and rotating the flask in a bath, called a shell freezer, which is cooled by mechanical refrigeration, dry ice and methanol, or liquid nitrogen. On a larger-scale, freezing is usually done using a freeze-drying machine. In this step, it is important to cool the material below its eutectic point, the lowest temperature at which the solid and liquid phases of the material can coexist. This ensures that sublimation rather than melting will occur in the following steps. Larger crystals are easier to freeze-dry. To produce larger crystals, the product should be frozen slowly or can be cycled up and down in temperature. This cycling process is called annealing. However, in the case of food, or objects with formerly-living cells, large ice crystals will break the cell walls (discovered byClarence Birdseye)†. Usually, the freezing temperatures ar e between -50  °C and -80  °C. The freezing phase is the most critical in the whole freeze-drying process, because the product can be spoiled if badly done. Amorphous (glassy) materials do not have an eutectic point, but do have a critical point, below which the product must be maintained to prevent melt-back or collapse during primary and secondary drying. 6.2 Primary drying: â€Å" Primary drying can reduce the moisture content of a freeze dried solid to around 0.5%. Further reduction can be effected by secondary drying. During the primary drying, the latent heat of sublimation must be provided and the vapour removed. enough heat is supplied to the material for the water to sublimate In this initial drying phase, about 95% of the water in the material is sublimated. This phase may be slow (can be several days in the industry), because, if too much heat is added, the materials structure could be altered†. 6.3 Secondary drying: The removal of residual moisture at the end o primary drying is performed by raising the temperature of the solid to as high as 50 °C or 60 °C. A high temperature is permissible for many materials because the small amount of moisture remaining is not sufficient to cause spoilage 6.4 Freeze drying advantages: Drying takes place at very low temperatures, so that enzyme action is inhibited and chemical decomposition, particularly hydrolysis, is minimised. The solution is frozen such that the final dry product is a net work of solid occupying the same volume as the original solution. Thus the product is light and porous. The porous form of the product gives ready solubility. There is no concentration of the solution prior to drying. Hence, salts do not concentrate and denature proteins, as occurs with other drying methods. As the process takes place under high vacuum there is little contact with air, and oxidation is minimized. 6.5 Freeze drying disadvantages: The porosity, ready solubility and complete dryness yield a very hygroscopic product. Unless products are dried in their final container and sealed in situ, packaging requires special conditions. The process is very slow and uses complicated plant, which is very expensive. It is not a general method of drying, therefore, but is limited to certain types of valuable products which, because of their heat sensitivity, cannot be dried by any other means. 7 Apparatus used for the experiment : 7.1 Uv_visible spectroscopy: â€Å" A diagram of the components of a typical spectrometer is shown in the following diagram. The functioning of this instrument is relatively straightforward. A beam of light from a visible and/or UV light source (colored red) is separated into its component wavelengths by a prism or diffraction grating. Each monochromatic (single wavelength) beam in turn is split into two equal intensity beams by a half-mirrored device†. One beam, the sample beam (colored magenta), passes through a small transparent container (cuvette) containing a solution of the compound being studied in a transparent solvent. The other beam, the reference (colored blue), passes through an identical cuvette containing only the solvent. The intensities of these light beams are then measured by electronic detectors and compared. The intensity of the reference beam, which should have suffered little or no light absorption, is defined as I0. The intensity ofthe sample beam is defined as I. Over a short perio d of time, the spectrometer automatically scans all the component wavelengths in the manner described. The ultraviolet (UV) region scanned is normally from 200 to 400 nm, and the visible portion is from 400 to 800 nm. [11] Components of UV_ visible spectroscopy 7.2 Instrumentation: Source of light: The best source of light that which is more stable more intense and which gives range of spectrum from 180-360nm.The different sources available are: Hydrogen discharge lamp:It is more stable robust and widely used.It gives radiation from 120-350nm.The lamp consist of hydrogen under pressure. Deuterium lamp: It is similar to hydrogen discharge lamp, but filled with deuterium in the place of hydrogen.It offers 3-5 times more intensity than other types.This is most widely used but expensive. Xenon discharge lamp: In this lamp, xenon at 10-30 atmospheric pressure is filled in and has two tungsten electrodes. The intensity is greater than hydrogen discharge lamp. Mercury arc: This contains mercury vapour and offers bands which are sharp.The spectrum is not continuous. Monochromaters: â€Å"Grating monochromaters are used, filters and prism monochromaters are not used because of low resolution.On the other hand gratings provide a band pass of 0.4 to 2nm.Hence they are more widely used incase of expensive spectrophotometers.The mirrors ,gratings are made up of quartz since glass absorbs uv radiation from 200-300nm.Mirrors are front surfaced to prevent absorption of radiation†. Sample Cells: â€Å"The design of sample cells used is similar to that used in colorimetry expect that it is made up of quartz. Quartz cells only must be used in uv spectroscopy since glass cells will absorb uv radiation.The pathlength of the cells are 10mm or 1cm†. Solvents: â€Å"solvent plays an important role in uv spectra, since compound peak could be obscured by solvent peak.Hence the solvent for a sample is selected in such a way that solvent neither absorbs in the region of measurement nor affects the absorption of the sample†. Detectors: Although any one of the detectors used in colorimetry can be used, photomultiplier tubes are mainly used, since the cost of such UV spectrophotometers are high and more accurate measurements are to be made. Single beam and double beam UV spectrophotometers are used. 7.3.Beers law (related to concentration of absorbing species): Beers law states that the intensity of beam of monochromatic light decreases exponentially with increase in the concentration of absorbing species arithmetically. Lamberts law (related to thickness/ path length of absorbing species): Lamberts law states that the rate of decrease of intensity (monochromatic light) with the thickness of the medium is directly proportional to the intensity of incident light. Beer-Lambert Law: The beer lamberts law states that absorbance of a solution is directly proportionally to the concentration of the solution. A = −log_{10}(I/I_0) = epsiloncdot ccdot L, The beer-lambert law is useful for characterizing of the compounds but does not hold as a universal relationship for the concentration and absorption of all species. Applications: It is mainly used in the detection of impurities. It is used in the structure elucidation of organic compounds. And also used in the analysis of organic compounds. Detrmination of molecular weight. Determination of dissociation constant of acids and bases. 7.4 Flow through dissolution apparatus: â€Å"The flow-through cell is a suitable method for dissolution studies of poorly soluble drugs. The dissolution can be influenced by changing parameters in the apparatus and by changing the physical properties of the drug and the medium used. In this study the dissolution of ibuprofen was examined†. Results showed that a smaller particle size gave a higher dissolution rate. With a dose of 50mg a higher percent dissolved was obtained compared to a dose of 100mg. However, a larger mass (mg) was dissolved when the dose of 100mg was used. When using a cell diameter of 12mm instead of a cell diameter of 22.6mm the dissolution rate increased. A larger dissolution rate was also obtained when the flow of the medium was increased. Finally the effect of changing medium was examined. Results showed that by including a surfactant to the medium a drastic increase of the dissolution rate was obtained. The flow-through cell has since the 90s been used as an alternative method for dissolution studies . It has some advantages over previous dissolution methods. It is easier to retain sink condition, i.e. to keep a sufficiently low concentration in the remaining solution. This makes it possible to keep a constant diving force (=concentration difference) the whole time during the release experiment. The concentration should not exceed one third of the saturated. The medium can be changed automatically during the study which is very useful in in vitro in vivo studies . Previous studies have showed the importance of deaeration of the dissolution medium, how the packing of the cell can influence the dissolution and that the results obtained with the flow-through cell are more reproducible than obtained with previous methods as dissolution baths In this study the dissolution of ibuprofen was examined in the flow-through cell. Six parameters were of interest: The packing of the cell The particle size of the drug The dose The volume flow of the medium through the cell The cell diameter The medium Desirable results were good reproducibility, i.e. small standard deviation between tests and cells, and to maintain sink condition during the experiment. Advantages : Laminar flow characteristics over a wide range of solvent flow rates Infinite sink ideal for low solubility drugs Differential rather than cumulative time profile o