Alfuzosin Hydrochloride and Dutasteride In Tablets

Alfuzosin Hydrochloride and Dutasteride In diggingssABSTRACTThis chapter describes method development and governance of UV outgrowth derivative instrument null overlap method for synchronic determination of Alfuzosin Hydrochloride and Dutasteride in oral contraceptive social disease embodiments.AIMThe main aim of the present study is to develope a simple, sensitive and cost good UV spectroscopic method for the synchronic estimation of Alfuzosin Hydrochloride and Dutasteride in tablets, on the behind of slide fastener Crossing measurement. Validation of the developed method for routine analysis of Alfuzosin Hydrochloride and Dutasteride in tablets for quality control laboratories.RATIONALEAlfuzosin Hydrochloride is an alpha-adrenergic blocking agent apply to finesse benign prostate hyperplasia (BPH). It performances by relaxing the musclebuilders in the prostate and vesica neck, making it easier to urinate Dutasteride belongs to a class of doses called 5-alpha-red uctase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Recently both the drugs abide been marketed in combination (Alfusin D acts on both the dynamic and the static functions of BPH) in tablet dosage forms combined oral administration has been found to be more effective than either single drug. To the best(p) of knowledge, no derivative spectroscopic method available for simultaneous determination. Derivative spectroscopy provides a greater selectivity than common spectroscopy.RESULT AND CONCLUSIONA simple, accurate and precise spectroscopic method was developed forsimultaneous determination of LER and take in tablets using first derivative zero in crossing method. LER shows ZCP at 231 nm while ATE shows ZCP at250 nm. The 1D amplitude was measured at 250 nm for LER and 231 nm ForATE and normalisation curves were plotted as 1D amplitude versus tightfistedness,respectively. The method was found to be linear from 4-28 g/mL for LER(r2=0.9967) at 250 nm and 5-30 g/mL for ATE (r2=0.9996) at 231 nm. Thewithin day and amidst day adaptations showed coefficient of variation (%CV) observes 1.2 LITERATURE REVIEW1.2.1 BENIGN PROSTATIC HYPERPLASIA (BPH)It is characterized by hyperplasia of prostatic stromal and epithelial cells, resulting in the physical composition of large, fairly discrete nodules in the periurethral region of the prostate. When sufficiently large, the nodules compress the urethral canal to cause partial, or virtuallytimes virtually complete, obstruction of the urethra, which interferes the normal flow of pee. It leads to symptoms of urinary hesitancy, frequent urination, dysuria (painful urination), increased risk of urinary tract infections, and urinary retention. Although prostate specific antigen levels may be elevated in these patients because of increased organ volume and inflammation due to urinary tract infections, BPH is not considered to be a premalignant lesion.Adenomatous prostatic conjureth is believed to begin at approximately age 30 years. An estimated 50% of men bewilder histologic evidence of BPH by age 50 years and 75% by age 80 years. In 40-50% of these patients, BPH becomes clinically significant.How does BPH occur?The prostate goes through two main periods of growth. In early puberty, the prostate doubles in size. Then, around age 25, the prostate begins to grow again and continues to grow throughout most of a mans life.The continuing enlargement of the prostate does not usually cause problems until afterward in life. However, the second period of growth may, many years later, result in BPH. According to the topic Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)BPH rarely causes symptoms before age 40.More than half of men in their 60s hurl close to symptoms of BPH.As many as 90 percent of men in their 70s and 80s have some symptoms of BPHSYMPTOMSDifficulty in starting to pass urine ( hesitancy)A wa shy current of urineDribbling after urinatingThe need to strain to pass urineIncomplete emptying of vesicaDifficulty to control the urination urgeHaving to get up several times in the iniquity to pass urineFeeling a burning sensation when passing urinePassing urine mixed with blood (indication of infection)Treatment of BPHBPH may not require any form of treatment and may just be monitored for any changes or early signs of any problems. In the cause that BPH has caused a urinary tract infection, the infection will be treated first with antibiotic medications and then the BPH may be treated.There are several forms of treatment that can be used for benign prostatic hyperplasia that include medications, minimally invasive therapies, and surgery. The two types of medications currently used to treat BPH are alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors. These medications can prevent the prostrate gland from growing larger and may shrink the prostrate gland in som e patients.How do Alpha blockers run shortAlpha blockers roleplay by relaxing the smooth muscle tissue in your prostate and at the opening to your bladder. When this muscle tissue relaxes, it is easier for your urine to flow. This may help if you have difficulty starting to urinate and a weak urine stream.Alpha blockers can start working within two to three days, and may placate your urinary symptoms in about two to three weeks. However, these medications do not stop your prostate gland from continuing to enlarge.Available alpha blockers includeCardura (doxazosin)Flomax (tamsulosin)Hytrin (terazosin)Uroxatral(alfuzosin)How do 5 alpha reductase inhibitors workThe 5-alpha reductase inhibitors work by interfering with the effect of specific male hormones (androgens) on your prostate. This may slow the growth of your prostate and can even cause your prostate to get smaller, which may help improve BPH symptoms. men with larger prostates may have a greater benefit from these medication s than do men with smaller prostates. But, for some men, size (of the prostate that is) does not matter, and the 5-alpha reductase inhibitors may not give satisfactory results even if your prostate gets smaller.The 5-alpha reductase inhibitors work slowly, and they may take up to six months before you notice any improvement.Available 5-alpha reductase inhibitors includeAvodart (dutasteride)Proscar (finasteride) some(pre titular) an Alpha Blocker and 5-alpha Reductase InhibitorDepending on symptoms and the size of your prostate, your doctor may recommend a combination of an alpha-adrenergic blocker with a 5-alpha reductase inhibitor. The combination of the two types of medications may help more than either medicine alone.1.2.2 DRUG visibilityAlfuzosin hydrochloride It is an alpha-adrenergic blockerStructureFileAlfuzosin.svgN-3-(4-amino-6,7-dimethoxy-quinazolin-2-yl)-methyl-aminopropyl tetrahydrofuran- 2-carboxamideDutasteride It is a 5-alpha-reductase inhibitor.StructureFileDutaster ide.svg(5,17)-N-2,5bis(trifluoromethyl) phenyl-3-oxo-4-azaandrost-1-ene-17-carboxamidePharmacodynamicAlfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the humane prostate, alfuzosin antagonizes phenylephrine (alpha(1) agonist)-induced contractionsPharmacokineticsand MetabolismAbsorption is 50% lower under fasting conditions account book of distribution 3.2 L/kg healthy male middle-aged volunteers Protein binding 82%-90% Metabolism Hepatic. Alfuzosin undergoes extensive metabolism by the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized by three metabolic pathways oxidation, O-demethylations, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the corpus hepatic enzyme isoform involved in its metabolism.1.2.3 REPORTE D UV SPECTROPHOTOMETRIC METHODS1.2.4 Aim and Objective of the present workDerivative spectroscopic methods are more sensitive than other spectroscopic method according to literature there is no derivative spectroscopic method reported so there is need to develop a sensitive derivative spectroscopic method which is more sensitive than simultaneous equation method so aim is to develop and validate the first derivative Zero-Crossing UV spectrophotometric method and apply that method to simultaneous determination of these drug in marketed formulation.1.3 EXPERIMENTAL WORK1.3.1 Chemicals and ReagentsAlfuzosin HCl and Dutasteride ALFUSIN D (CIPLA Ltd.) containing 10 mg of Alfuzosin HCl 0.5 mg of Dutasteride were purchased from local anesthetic market. Methanol of HPLC grade was purchased from Merck Ltd. (Mumbai, India). Purified Water was lively using a Millipore Milli-Q system (Bedford, MA, USA).1.3.2 InstrumentSpectroscopic abridgment was carried out on a JascoV-650 double beam UV-V isiblespectrophotometer with software of Spectra Manager. The zero gild denseness spectra were put down over the wavelength crease of 200-400 nm, against solvent blank, in quartz cuvetts with 1 cm diameter with scan fixity of 100 nm/min and fixed value of slit width is 1 nm The invest maximum minimum were adjusted according to derivative determine.1.3.3 Development of UV first derivative Zero crossing methodAs the Dutasteride is Insoluble in Water 8020 V/V Mixture of Methanol and Water were used for method development First of all, Individual Zero orders absorption Spectra of both the drugs were recorded by scanning 10 g/ml issue. The max of Alfuzosin HCl and Dutasteride was found to be 240 nm 225.5 nm respectively. We have chosen derivative spectroscopy which is based on mathematical mutation of spectra zero order curves in to derivative spectra, which allows a fast sensitive and precise resolution of a multicomponent categorisation and overcomes the problem of overlapp ing of a multi component system. Derivative Spectroscopy on the basis of zero crossing measurement involves measurement of absolute value of total derivative spectrum at an abscissa value jibe to the Zero Crossing wavelength of the derivative spectra of individual components, which should be only the function of the dousing of the other component. Zero crossing blots of Alfuzosin HCl and Dutasteride were identified in first derivative spectra. the measurement debunked the best linear response and have given a near zero intercept on the coordinate of the calibration graph, and is less abnormal by the concentration ofany other component. Alfuzosin HCl was heady by measurement of its 1D amplitude at the zero-crossing point of Dutasteride was determined by measurement of its1 D at the zero-crossing point of Alfuzosin HCl .1.3.4 Preparation of stock solution radical standard stock solution of Alfuzosin HCl and Dutasteride were prepared separately by dissolving accurately weighed am ount (10 mg) of drug in 10 ml 8020 V/V (MeOHH2O) to produce a concentration of 1.00mg/mL Working standard solution of each analyte were prepared by appropriate dilution of stock solution to get 100 g/mL The further concentration required for constructing calibration curve were prepared daily by dilution of 100 g/mL working standard. Stock solution of binary kind was prepared by dissolving accurately weighed quantities of both drugs in solvent. Further dilutions of binary mixture were make to restrain QC savours.1.3.5 Calibration standard quality control (QC) samplesThe standard calibration sample were prepared by diluting working standard solution of each analyte to yield seven different concentration over the range of3-24 g/mL for Alfuzosin HCl 3-30 g/mL for Dutasteride . Linearity was evaluated separately for each drug using the delimitate analytical amplitudes (1D), with appropriate seven standard solutions. The QC sample were prepared from stock solution containing binary mixture to yield the low, medium high concentration (4,5 6g/ml for Alfuzosin HCl) (20 ,25 30 g/mLfor Dutasteride).1.3.6 mental process for calibration curveAbsorption derivative spectra were recorded over the range of the wavelength range 200-400 nm. Zero order spectra of standard calibration sample of 10 g/ml of each drug were recorded against blank. First order spectra were recorded with in concentration range, the value of analytical amplitude 1D231 and 1D250 for ATE LER respectively were recorded. The calibration curve for derivative spectrophotometry were constructed by plotting the drug concentration versus the absorbance values of the first derivative spectrum 1D at 1D 231 and 1D250 for ATE LER, respectively.1.3.7 Inter-day Intra-day accuracy precisionA QC standard prepared binary mixture was evaluated for Inter-day Intradayaccuracy precision. Accuracy was determined as the absolute value of the ratio of the back calculated mean values of QC to their respective n ominalvalues was expressed as percentage. Precision of assay was expressed aspercentage coefficient of variation (% CV) for QC sample Binary Mixture1.3.8 Assay of pharmaceutical dosage formA total number of 20 tablets (Alfusin D) accurately weighed andpowdered in a mortar. Quantities of the powdered tablets equivalent to 10 mg of Alfuzosin HCl 0.5 mg of Dutasteride were accurately weighed and transferred in to 100 ml volumetric flask. Weighed powder was dissolved in 8020 V/V (MeOHH2O) mixed thoroughly and kept under mechanical shaking for 15 minutes. Solution obtain was filtered through filter paper and diluted with same solvent to get the concentration within linearity and used for the measurement of derivative spectra. The concentration of Alfuzosin HCl and Dutasteride in tablet were calculated from corresponding calibration curve.1.4 RESULTS AND intelligence1.4.1 Development of First derivative zero crossing methodDerivative spectroscopy on the basis of zero crossing measure ment involves measurement of absolute value of total derivative spectrum at an abscissavalue corresponding to the zero crossing wavelengths of the derivative spectraof individual components. Which should be the function of the concentration ofother component Zero crossing points for ATE LER were found to be 211.9,225.4, 250, 275.2, 292.2 218.4, 231, 240.7, 310.9, 362.7 nm respectively themeasurement at 250 231 exhibit best linear response. So ATE wasdetermined by measurement of its 1D amplitude at ZCP of LER (at 231 nm ).LER was determined by measurement of its 1D amplitude at ZCP of ATE (at250 nm).1.4.2 Validation23-251.4.2.1 LinearitySince beer law obeys between absorbance values 0.1-1, the linearity isestablished by plotting points between these two readings in reproduce. forLercanidipine HCl linearity found to be between 3 g/mL to 24 g/mL withtypical retroflection equation of 0.0015x-0.0003 with regression coefficient of0.9967 for Atenolol Linearity found to be between 3 g /ml to 30 g/ml withregression equation 0.0025x+0.0005 with regression coefficient of 0.9996.1.4.2.2 AccuracyThe accuracy of method was established in triplicate in three consecutive days. At 80%, 100% 120% of the expected sample concentration in synthetic binary mixture, the method found to be very accurate with recoveryReferencesM. VAMSI KRISHNA* and D. GOWRI SANKAR optimisation and Validation of Quantitative Spectrophotometric Methods for the mark of Alfuzosin in Pharmaceutical Formulations ISSN 0973-4945 CODEN ECJHAO E-Journal of ChemistrySafwan Ashour, M. Fawaz Chehna, Roula Bayram Spectrophotometric Determination of Alfuzosin HCl in Pharmaceutical Formulations with some Sulphonephthalein Dyes International journal of Biomedical scienceM. SUGUMARAN Extractive Spectrophotometric Determination of Alfuzosin from Its Bulk and Pharmaceutical Dosage Form J. Ind. Council Chem. Vol. 26, nary(prenominal) 1, 2009, pp. 47-49SYEDA HUMAIRA, AKALANKA DEY1, S APPALA RAJU, SYED SANAULLAH A pplications Of Colorimetric Methods For The Determination Of Cinitapride Hydrogen Tartarate In Drug Formulations International Journal of Pharmacy and Pharmaceutical Sciences Vol 2, Suppl 1, 2010Md Ruhul Amin, Moynul Hasan, Abdullah Al Masud, Md Hanif uddin,Md Hasanuzzaman and Mohammad Kaisarul Islam Validated Uv Spectrophotometric Method For Estimation Of Dutasteride In Tablet Dosage Form Islam M K et al. / Pharmacie Globale (IJCP) 2011, 4 (04)Kamila M. M., Mondal N Ghosh L.K A Validated Spectrophotometric Method ForDetermination Of Dutasteride In Bulk Drug And Pharmaceutical Formulations International Journal of PharmTech Research CODEN (USA) IJPRIF ISSN 0974-4304Vishnu P. Choudhari*, Sacchidanand R. Gite, Rahul P. Raut, Asawaree A. Hable, Sanket R. Parekar, Bhanudas S. Kuchekar Spectrophotometric Simultaneous Determination Of Dutasteride And Tamsulosin In Combined Tablet Dosage Form By First Order Derivative Spectroscopy And neighborhood Under Curve (Auc) Spectrophotometric Met hods And Its Application To Uniformity Of Content In Tablet And Capsule ISSN 0976 -044 x Volume 2, Issue 2, May June 2010 Article 013