Levocetrizine Dihydrochloride and Ambroxol Hydrochloride

Levocetrizine Dihydrochloride and Ambroxol HydrochlorideSIMULTANEOUS ESTIMATION OF LEVOCETRIZINE DIHYDROCHLORIDE AND AMBROXOL HYDROCHLORIDE IN SYRUP DOSAGE FORM BY USING UV SPECTROPHOTOMETRIC METHODS. S. Pekamwar, Madhav ShelkeABSTRACT A sincere, economical, rapid, accurate and precise UV Spectrophotometric order was genuine for simultaneous estimation of Levocetrizine dihydrochloride and Ambroxol hydrochloride in bulk and in Syrup formulation. Determination of Levocetrizine dihydrochloride (LCTZ) and Ambroxol hydrochloride (AMB) in bulk and in sirup was conducted by using simultaneous equation mode based on measurement of absorbance at 246 nm and 231 nm, max of LCTZ and AMB, respectively. The solvent used for proposed method was methanol pee (5050). The linearity for LCTZ and AMB was in the range of 5-35 g/ml and 5-50 g/ml, respectively. The developed method was validated as per ICH guidelines. The % recovery was found to be in the range of 99.52- 99.82% and 100.37- 100.72% fo r LCTZ and AMB, respectively. Thus the proposed method was simple, rapid, reproducible and accurate and can be successfully utilize for simultaneous estimation of Levocetrizine dihydrochloride and Ambroxol hydrochloride in bulk and in Syrup formulation.KEYWORDS Levocetrizine dihydrochloride, Ambroxol hydrochloride, coinciding Equation system, UV Spectrophotometry, Syrup, Validation.INTRODUCTION Levocetirizine is a third generation non-sedative antihistamine. Chemically, levocetirizine is the active enantiomer of cetirizine. It is the L-enantiomer of the cetirizine racemate. Levocetirizine toys by blocking histamine receptors. Levocetrizine is chemically, (R)-2-2-4-(4- chlorophenyl)phenylmethyl piperazin-1-yl ethoxy acetic acid dihydrochloride.Chemical Structure of Levocetrizine dihydrochlorideAmbroxol is an active N-desmethyl metabolite of mucolytic bromhexine. Ambroxol is used as a bronchosecretolytic and expectorant drug. Ambroxol has been shown to increase the quantity and m itigate the viscosity of respiratory tract secretions. It enhances pulmonary surfactant production (surfactant activator) and stimulates ciliary motility. These actions result in improved mucus flow and transport (mucociliary clearance). Enhancement of quiet secretion and mucociliary clearance facilitates expectoration and eases cough. Ambroxol is chemically, trans-4-(2-Amino-3,5-dibromobenzyl)amino cyclohexanol hydrochloride.Chemical Structure of Ambroxol hydrochlorideLiterature survey revealed that various analytical methods involving UV Spectrophotometry, HPLC and HPTLC have been reported for LCTZ and AMB alone and in combining with other drugs. However there is no method developed for simultaneous estimation of Levocetrizine dihydrochloride and Ambroxol hydrochloride in liquid dosage form (Syrup). The objective of present work was to develop simple, rapid, economical accurate and precise analytical method for simultaneous estimation of Levocetrizine dihydrochloride and Ambroxol hydrochloride in bulk and in liquid dosage form (Syrup). The developed method was validated in accordance with ICH guidelines and successfully employed for the assay of LCTZ and AMB in combined liquid dosage form (Syrup).MATERIALS AND METHODSChemicals and Reagents Analytically, pure LCTZ and AMB were provided as bounty sample by Bidwai Chemicals Pvt. Ltd. Nanded and Glen hybridization Pharmaceuticals, Mumbai, Maharashtra, respectively. Syrup of LCTZ and AMB, Mzic D manufactured by Monad Pharmaceuticals, were purchased from local pharmacy. Methanol AR grade (Molychem) and Distilled water was used throughout the data-based work.Instruments A UV-Visible Spectrophotometer Shimadzu, Model UV-1800 with 1 cm matched quartz cell and UV Probe 2.33 software was used. Calibrated analytical balance Anamed was used for weighing purpose. digital Ultrasonic Cleaner (Sonicator) HMG India and Vaccum Pump Assembly Millipore was used for the experimental work. breeding Standard Stock SolutionAmbrox ol hydrochloridre well-worn stock solutionAccurately weighed point of reference standard of AMB (10mg) was transferred to 100ml volumetric flask and dissolved in 50 ml solvent (Water, methanol 11) and sonicate for 5 min. then volumes was make up to the mark with aforesaid(prenominal) solvent to obtain standard stock solution (100g/ml) of drug. For the preparation of working standards, suitable aliquots of stock solution were pipette out and volumes were made up to the mark with solvent (Water, methanol 11) so as to get required concentrations.Levocetrizine dihydrochloride standard stock solutionAccurately weighed reference standard of LCTZ (10mg) was transferred to 100ml volumetric flask and dissolved in 50 ml solvent (Water, methanol 11) and sonicated for 5 min. then volumes was made up to the mark with same solvent to obtain standard stock solution (100g/ml) of drug. For the preparation of working standards, suitable aliquots of stock solution were pipette out and volumes were made up to the mark with solvent (Water, methanol 11) so as to get required concentrations.Selection of analytical wavelengthSample solutions were scanned over the wavelength range of 200 nm to 400 nm, max for AMB and LCTZ were found at 231 nm and 246 nm. Representative absorption spectra of AMB and LCTZ are shown in fig. 1 2.Fig. 1 Absorption Spectra of LCTZFig. 2 Absorption spectra of AMBPreparation of calibration curve of AMB and LCTZBy appropriate dilution of standard stock solution, different dilutions were nimble ranging from 5g/ml to 35g/ml for LCTZ and 5 g/ml to 50 g/ml for AMB. Absorbance of all the dilutions was plotted against the respective concentrations to obtain the calibration curves. The absorption overlain spectrum of AMB and LCTZ is shown in fig. 3Fig. 3 cut across Spectra of LCTZ AMBFig. 4 Calibration Curve of LCTZFig. 5 Calibration Curve of AMBAnalysis of Marketed Syrup FormulationTen syrup bottles were weighed accurately, average weight was determined and poured in calibrated measuring cylinder to check extractable volume. As per label claim syrup contain LCTZ 5mg/5ml and AMB 30mg/5ml, so 5ml syrup was pipette out in 100 ml volumetric flask and dissolved in water methanol (11) solution, sonicated for 10 min and filtered. Then different concentrations of syrup sample were prepared by serial dilution method and used for analysis. Prepared syrup sample was analysed on UV spectrophotometer using Simultaneous Equation Method.Method ValidationThe method validation parameters linearity, precision, accuracy, repeatability, limit of detection and limit of quantitation were checked as per ICH guidelines. clearcutness Precision of the method was verified by using syrup stock solution, the repeatability indicates the cognitive process of the UV instrument. Inter sidereal day and intraday precision was determined by repeating the assay three times in same day for intraday precision and on different day for interday precision studies.Accuracy (Recovery Study) To check the accuracy of proposed method, recovery studies were carried out at 80%, 100% and 120% of the test conc. As per ICH guidelines.To perform recovery hold at 100%, 5ml syrup pipette out in volumetric flask and to this standard 30mg AMB and 5mg LCTZ was added. The volume as made up to the mark with water methanol (11) solution and further dilution with same solvent to obtain sample solution Similarly, for 80% recovery written report, 26mg AMB and 4mg LCTZ were added, and for 120% recovery study, 36mg AMB and 6mg LCTZ were added respectively.RESULTS AND DISCUSSIONPrecisionIntraday PrecisionSr. no.Interval ofConcentration (g/ml)% RecoveryTimeAMBLCTZI30.104.96100.3499.35IIIntra-day29.954.9599.8499.28III30.204.97100.6899.54Table 1 Intra-day Precision data of marketed formulationName of the drug regard as*SD%RSDAMB100.280.42250.4213LCTZ99.400.13450.1353* Indicates average of three determinationsTable No. 2 Statistical validation of intra-day precision dataIn ter-day PrecisionSr. No.Interval ofConcentration (g/ml)% RecoveryTimeAMBLCTZAMBLCTZI30.144.98100.4599.79IIInter-day30.094.98100.3299.72III29.964.9899.8799.63Table 3 Inter-day Precision DataName of the drugMean*SD%RSDAMB100.210.30430.3036LCTZ99.710.08020.0804* Indicates average of three determinationsTable 4 Statistical validation of inter-day precision dataAccuracy (Recovery study)Level of Recovery tot up present(mg/5ml)Added concentration (mg)Amount recovered(mg)% RecoveryAMBLCTZAMBLCTZAMBLCTZAMBLCTZ30524454.318.97100.5899.7480%30524454.208.95100.3899.5230524454.388.98100.7299.8230530560.289.96100.4799.68100%30530560.329.97100.5499.7030530560.229.95100.3899.5430536666.3110.96100.4899.69120%30536666.3610.96100.5699.7230536666.2410.95100.3799.58Table 5 Recovery study dataLevel ofrecovery% Mean recoveryS.D.% R.S.D.AMBLCTZAMBLCTZAMBLCTZ80%100.5699.700.17080.15530.16980.1557100%100.4699.640.08020.08710.07980.0874120%100.4799.670.09530.07370.09480.0951Table 6 Statistical validation o f recovery study dataLimit of Detection and Limit of QuantitationName of the drugLOD g/mlLOQ g/mlAMB3.16459.5896LCTZ3.08919.3611Table 7 LOD LOQCONCLUSIONThe method used is simple and rapid and does not involve the use of complex instrument, low value of Standard deviation showed that the method is precise and high percentage of recovery of as shown in table shows that the method is accurate. 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