Nebivolol

A rapid and sensitive LC-MS/MS method for the quantification of nebivolol using d4- nebivolol as internal standard has been developed and validated. The nebivolol and d4- nebivolol were extracted by liquid- liquid extraction using tert-butyl ethyl ether and separated on Kromasil 100-5C 4.6x100mm column using a mixture of 0.1% formic acid in 5 mM ammonium acetate, methanol and acetonitrile at composition of (20:20:60 v/v) at a flow rate of 0.5 mL/min. Detection involved an API-4000 LC-MS/MS with electrospray ionization in the positive mode.  The method was validated as per the FDA guidelines and shown to provide an intra and inter day precision and accuracy within the acceptable limit with in a run time of 3.0 min. The proposed method can adopt for the regular bioequivalence study analysis and also can easily adoptable for clinical drug monitoring due to its simplicity and ruggedness.

An attempt was made to formulate and evaluate the Nebivolol HCl transdermal drug delivery system. The matrix type films were prepared by using solvent casting technique with polymers HPMC 15cps,PVP K-30,Eudragit RL100 and Methyl cellulose 15cps.Propylene glycol was used as plasticizer. The prepared films were evaluated for physicochemical characteristics such as thickness, weight variation, folding endurance, % moisture uptake and % moisture loss. The drug excipient compatibility was determined by Fourier Transform Infra red Spectroscopy. The results revealed that there were no interaction between drug and selected polymers. In vitro permeation studies were performed in Franz diffusion cell using commercial semi permeable membrane. Ex vivo studies were performed using skin of albino rats. Biological studies such as skin irritation test and % drug diffusion studies were carried out by using rabbits. Drug content varied from 73.72 ± 0.1to 95.4±0.15%. Moisture content and moisture uptake were increased for patches containing higher amount of HPMC due to its hydrophilic nature. The batch F4 (HPMC 1.5%, PVP 0.5%) had shown drug release for 24 h to the extent of 86.87% and drug release followed zero order release kinetics which was of non-Fickaian type of diffusion. The results of ex vivo and in vivo studies were well correlated with in vitro diffusion studies

The present manuscript describe simple, sensitive, rapid, accurate, precise and economical first derivative spectrophotometric method for the simultaneous determination of nebivolol and hydrochlorothiazide in combined tablet dosage form. The derivative spectrophotometric method was based on the determination of both the drugs at their respective zero crossing point (ZCP). The first order derivative spectra were obtained in methanol and the determinations were made at 270.5 nm (ZCP of hydrochlorothiazide) for nebivolol and 282.5 nm (ZCP of nebivolol) for hydrochlorothiazide. The linearity was obtained in the concentration range of 5-100 μg/ml for nebivolol and 2-14 μg/ml for hydrochlorothiazide. The mean recovery was 100.04 + 0.93 and 99.87 + 1.16 for nebivolol and hydrochlorothiazide, respectively. The method was found to be simple, sensitive, accurate and precise and was applicable for the simultaneous determination of nebivolol and hydrochlorothiazide in pharmaceutical tablet dosage form. The results of analysis have been validated statistically and by recovery studies. Key words: Nebivolol, hydrochlorothiazide, recovery, first order derivative spectrophotometric method, tablet, validation.

  The present manuscript describe simple, sensitive, rapid, accurate, precise and economical first derivative spectrophotometric method for the simultaneous determination of nebivolol and hydrochlorothiazide in combined tablet dosage form. The derivative spectrophotometric method was based on the determination of both the drugs at their respective zero crossing point (ZCP). The first order derivative spectra were obtained in methanol and the determinations were made at 270.5 nm (ZCP of hydrochlorothiazide) for nebivolol and 282.5 nm (ZCP of nebivolol) for hydrochlorothiazide. The linearity was obtained in the concentration range of 5-100 μg/ml for nebivolol and 2-14 μg/ml for hydrochlorothiazide. The mean recovery was 100.04 + 0.93 and 99.87 + 1.16 for nebivolol and hydrochlorothiazide, respectively. The method was found to be simple, sensitive, accurate and precise and was applicable for the simultaneous determination of nebivolol and hydrochlorothiazide in pharmaceutical tablet dosage form. The results of analysis have been validated statistically and by recovery studies.     Key words: Nebivolol, hydrochlorothiazide, recovery, first order derivative spectrophotometric method, tablet, validation.