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pharmaceutical surfactants on Cytochrome (CYP P450) Assignment

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Added on  2019-12-04

pharmaceutical surfactants on Cytochrome (CYP P450) Assignment

   Added on 2019-12-04

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Influence of pharmaceutical surfactants onCytochrome (CYP P450) enzymes
pharmaceutical surfactants on Cytochrome (CYP P450) Assignment_1
Table of ContentsBACKGROUND..................................................................................................................................4AIMS, OBJECTIVES AND RESEARCH QUESTION ....................................................................6RATIONALE .......................................................................................................................................6MATERIAL AND METHODS ...........................................................................................................7DISSEMINATION STRATEGY..........................................................................................................9RESOURCES AND BUDGETS .......................................................................................................10PROPOSED TIME SCALE FOR THE COMPLETION OF THE PROJECT .................................10REFERENCES...................................................................................................................................12
pharmaceutical surfactants on Cytochrome (CYP P450) Assignment_2
ABSTRACTThe aim of the study is to examine the capability of these non-ionic surfactants such aPolyoxyethylene glycolalkyl ethers: CH3–(CH2)10–16–(O-C2H4)1–25–OH:Octaethylene glycolmonododecyl etherPentaethylene glycol monododecyl ethePolyoxyethylene glycolalkyl ethers (: CH3–(CH2)10–16–(O-C2H4)1–25–OH:Octaethylene glycolmonododecyl etherPentaethylene glycol monododecylenzymes of the cytochrome P450 superfamily in vitro. To meet the objectives of the study human liver microsomes will be utilized whichwill examine their inhibitory effects on the isoenzymes cytochrome P450 3A4 (CYP3A4) and 2C9(CYP2C9). This is considered to be one of the most important enzyme that is used for themetabolism of all almost all the drugs in the liver and intestine. In previous studies that have beenconducted on impact of pharmaceutical surfactants on cytochrome P450 it was noticed thatsequences of intestinal and hepatic cytochrome P450 3A4 cDNAs (complementarydeoxyribonucleic acids) were identical. Testosterone and diclofenac will be the specific substratesthat will be used in this experiment. The overall study will be based on HPLC analysis which willutilise hydroxylation of radio-labelled testosterone into 6b- hydroxytestosterone in HPLC machine. A Hypersil Gold (5 l m; 125 # 3.0 mm) C18 column from Ercatech (Bern, Switzerland) willbe used.Further the eluent used in experiment will be acetonitrile and water with 0.2%trifluoroacetic acid/acetonitrile 95:5. Gradient analysis will also be conducted and the ratio ofdifferent mobile phases that will be used in the study will be 3:97, 50:50, 95:5 (staying isocratic for1 min) and 30:70 at 0, 20, 21, and 23 min. For the process of data analysis software Chromeleon6.5.0 (Dionex; Sunny-vale, USA) will be used. To determine the metabolite 4-hydroxydiclofenac,HPLC-MS (API3000 from Applied Biosystems; Foster City, USA) will be used. A Synergi Polar-RP (4 l m; 75 # 2.0 mm) from Phenomenex (Aschaffenburg, Germany) and an Atlantis dC18 (3 l m;2.1 # 10 mm) from Waters (Milford, USA) as pre-column will be applied for analysis so that moreaccurate results are produced. In the overall procedure the mobile and the stationary phase will be constant so thatchemical and physical variations do not takes place in the HPLC analysis. Mobile phase for thisexperiment will be acetonitrile with 0.1% formic acid and water with 0.1% formic acid. Forgradient analysis, the ratios of the mobile phases were varied to 3:97, 50:50, 70:30 (remainingisocratic for 0.7 min), and 3:97 at 0, 1.8, 1.9, and 2.9 min. or data analysis, the software Analyst1.4.1 (Applied Biosystems; Foster City, USA) will be utilized. Interactions of cytochrome P450enzymes with common formulation ingredients like non-ionic surfactants will be estimated so thatimpact can be concluded. From the experiment it can evaluated that it is very necessary to actcautiously when applying all the solubilizing agents in the pharmaceutical industry. If these cautionsare not maintained that it will lead to rise in absorption rate and may also increase the risk of
pharmaceutical surfactants on Cytochrome (CYP P450) Assignment_3
assessing incorrect pharmacokinetic parameters for new drug entities. This can also be used in orderto increase the bio availability of orally administered drugs that are reported to be the substrates ofcytochrome P450 enzymes. Drug products are mainly composed of two types of substances namelythe active pharmaceutical ingredient and the excipients. Depending upon the functionalclassification and roles in the resultant formulation they can be categorized as diluent, disintegrants,binders, lubricants and glidants. Lactose is the finest examples of binder excipients that is used inwet granulation so that it allows better mixing and granule quality. Pregelatinised starch and crosslinked PVP are also some common excipients that play a role in granulation process so that moreeffective granules are formed.BACKGROUNDPharmaceutical excipients can be broadly defined as substances other thanpharmacologically active drugs or pro-drugs that are used in manufacturing process of various soliddosage forms (Martin and et.al, 2013). They play a major role in modulating the solubility and bio-availability of active pharmaceutical ingredients in the drugs. Stability of active ingredients is alsoincreased due to the pharmaceutical excipients used in designing different dosage forms. They arealso designed so that they are able to maintain polymorphic forms and conformations of the drug inpreferred manner. They are also helpful in maintaining the pH and osmolarity of liquid formulationsso that the amount of water retained in the drug is to a desired level. One of the major role ofpharmaceutical excipients is that they act as antioxidants, emulsifiers, aerosol propellants, bindersfor the tablets and as a disintegrant (Zhang and et.al, 2016). Preventing aggregation and dissociationis also one of the major role. For example proteins and polysaccharides helps in preventingaggregation to a considerable level in solid dosage forms. Different types of excipients used inpreparation of pharmaceutical ingredients are anti adherents, binders, coatings, colours,disintegrants, flavours, glidants, lubricants, preservatives, sorbents sweeteners and vehicles. Anti adherents can be defined as those substances that are utilised in lowering down theadhesion rate between granules of the tablets that are being punched in the punching machine. It isusually done to minimise the sticking which can hamper the quality of tablets produced after theprocess of punching. Similarly, binders are also a class of excipients that are used in the preparationof pharmaceutical formulations. Its main purpose is to develop a holding capacity between tabletsso that they can be formulated easily. (Huang and et.al, 2014). It ensures that all the tablets andpowder forms are prepared with equal mechanical strength. It also provides volume and quantity todoses form which have low active doses in them. They can be derivatives of saccharides such asdisaccharides, lactose, sucrose, polysaccharides and their derivatives namely starch, cellulose andmicrocrystalline cellulose. Cellulose ethers such as hydroxypropyl cellulose is also commonly used
pharmaceutical surfactants on Cytochrome (CYP P450) Assignment_4

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