Stability Indicating Method for the Determination of Related Substances in Felodipine Solid Dosage Form and in the Drug Substance by RP-HPLC

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Background: Methods were not available in the monographs like United States Pharmacopeia, British pharmacopeia and European pharmacopeia and also in the literature for the determination of three related impurities namely Impurity A, B and C in Felodipine solid dosage form with a shorter runtime using RP-HPLC. Method: A simple RP- HPLC method was developed and validated for the quantification of Felodipine Impurity A, B and C in Felodipine solid dosage form and in drug substance. This method was developed on waters alliance using Phenomenex Gemini column C18 5 μm,150 × 2.0 mm i.d, using the isocratic program with the mobile phase ratio of 0.02 mM ammonium acetate adjusted to pH 5 and acetonitrile (55:45,v/v) with a flow rate of 0.7 mL/min. The λmax is at 240 nm. Results: Forced degradation was performed as per ICH guidelines and no interference of the impurities with the known peaks was found. Precision was found between 0.1 and 0.2%. The Limit of detection and quantification for Felodipine and impurity A; Impurity B and C were 0.05 and 0.15 μg/mL respectively. The linearity correlation coefficient was found to be >0.999 for Impurity A and Felodipine; Impurity B and C of concentration range 0.2-30.0 μg/mL and 0.2-8.0 μg/mL respectively. The method accuracy was assessed for Felodipine and its impurities at four levels (LOQ, 50%, 100% and 150%) and the recovery ranged from 95% to 106%. Conclusion: The method was found to be precise, reliable, accurate and robust.

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... [2][3][4][5][6] There is a need for a simple, rapid, cost effective and reproducible method for assay of FEP in its dosage forms. A literature survey revealed that several HPLC [7][8][9][10][11][12][13][14][15] , SFC. [16] References [17][18] are helpful in performing validation properly and HPTLC in combination reported [19][20] but no HPTLC method reported for stability study of FEP. Therefore, it was thought of interest to develop simple, rapid, accurate, specific and precise HPTLC method for the analysis of felodipine (FEP) in its tablet formulation. ...
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A simple and sensitive, HPTLC method has been developed for the quantitative estimation of felodipine in it’s single component tablet formulation. The separation was carried out on Merck aluminium plates precoated with silica Gel 60 F254 using n -hexane: ethyl acetate in the ratio of 6:4 (v/v) as mobile phase. Felodipine showed Rf value of 0.53 ± 0.027 and was scanned at 366 nm using Camag TLC Scanner 3. The linear regression data for the calibration plot showed a good relationship with r=0.9792. The method was validated for precision and recovery. The limits of detection and quantification were 23.54 and 71.33 ng/spot respectively. The developed method was successfully used for the assay of felodipine tablet formulations. The method is simple, sensitive and precise; it can be used for the routine quality control testing of marketed formulations.
... This technique is a variation of conventional wet granulation technique. This technology is widely used in granulation of moisture sensitive active pharmaceutical ingredients 37 . This process involves the utilization of very little granulating fluid, to activate granule formation and it also eliminates the drying steps by using moisture absorbing materials like microcrystalline cellulose, potato starch, a mixture of MCC and potato starch (50% w/w to remove excess of moisture present in the granulate. ...
Granulation is a size enlargement process, in fine or coarse particles converted into physically stronger and larger agglomer ates having good flow property, better compression characteristics and uniformity, prevent segregation of the blend components, improve content uniformity, and eliminate excessive amounts of fine particles. Size of granules has a size range of 0.2 to 4. 0 mm, depending on their subsequent use. Size of the granules depends on the quantity and feeding rate of granulating liquid. The selection of process to prepare granules requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. At current scenario available technologies includes, spray drying, roller compaction, high shear mixing, and fluid bed granulation etc. The objective of present work is to focus on the commonly used and novel granulation technologies like such as pneumatic dry
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A rapid, simple and sensitive synchronous specrtofluorimetric method has been developed for the simultaneous analysis of binary mixture of metoprolol (MTP) and felodipine (FDP). The method is based upon measurement of the synchronous fluorescence intensity of the two drugs at Δλ of 70 nm in aqueous solution. The different experimental parameters affecting the synchronous fluorescence intensities of the two drugs were carefully studied and optimized. The fluorescence intensity-concentration plots were rectilinear over the ranges of 0.5-10 μg/mL and 0.2-2 μg/mL for MTP and FDP, respectively. The limits of detection were 0.11 and 0.02 μg/mL and quantification limits were 0.32 and 0.06 μg/mL for MTP and FDP, respectively. The proposed method was successfully applied for the determination of the two compounds in their commercial tablets and the results obtained were favorably compared to those obtained with a comparison method.
In this study, felodipine was incorporated into microparticles prepared with Eudragit® E and it blended with poly(3-hydroxybutyrate) (PHB) using the emulsion-solvent evaporation technique, with the aim of improving the dissolution rate of the drug. The formulation prepared with Eudragit® E showed irregular and fragmented microparticles, with a loading efficiency (LE) of 82.6%. When the microparticles were prepared with a blend of Eudragit® E and PHB, they had a spherical form with a LE of 103.9%. X-ray diffraction and differential thermal analysis indicated a reduction in the crystallinity of felodipine after its incorporation into the microparticles, which caused a significant increase in the felodipine dissolution rate. An investigation into the absorption in rats was carried out using high-performance liquid chromatography analysis of the blood collected 20 and 60 min after the animals were administered felodipine [30 mg/Kg, orally (p.o.)] or felodipine microparticles (30 mg/Kg, p.o.). Animals that were given felodipine showed mean plasmatic levels of 0.0125 (±0.00156) and 0.0240 (±0.0069) μg mL(-1) after 20 and 60 min, respectively, whereas animals that received microparticles containing felodipine showed respective mean plasmatic levels of 0.0651 (±0.0120) and 0.0369 (±0.0145) μg mL(-1) . Our data suggest that the incorporation into microparticles significantly enhanced the release of felodipine, improving its absorption in rats.
The most important steps in the validation of high-performance liquid chromatographic (HPLC) methods are discussed. The establishment of system suitability data and the assessment of peak purity are demonstrated on the example of bisquaternary amino steroids. For the recognition of incomplete resolution of adjacent peak pairs, the absorbance-ratio method in which the ratio of absorbances at two preselected wavelengths are plotted as a function of time in combination with the separation of sample components subjected to various chemical and physico-chemical treatments (stress conditions) is applied. The separation power and performance of the HPLC systems are characterized by the system resolution (SR) and system selectivity (SS). The special demands of stability-indicating methods are summarized.
The effect of felodipine [4-(2,3-dichloro-phenyl)-1,4-dihydro-2,6-dimethyl-3-ethoxycarbonyl-5- methoxycarbonylpyridine on the contractile responses of mesenteric resistance vessels denervated in vitro was investigated. Sustained contractions of this vessel type were totally dependent on extracellular calcium. Felodipine (10-(15)-10-(9)M) had a concentration-dependent inhibitory action on contraction induced by maximal potassium (125 mM) and noradrenaline (10-(5)M) stimulation. Felodipine was more potent and more selective than D600 and nifedipine. Potassium and noradrenaline concentration-response characteristics were insurmountably antagonized by felodipine, the potassium sensitivity of vessels being unaffected while noradrenaline sensitivity was decreased. In calcium-depleted vessels, felodipine in all concentrations tested produced insurmountable antagonism of the potassium-activated calcium concentration-response characteristics, whereas the antagonism in low concentrations (10-(15)-10-(11)M) was surmountable in noradrenaline-activated vessels. Felodipine 10-(9) M blocked the response of potassium-activated vessels almost completely, whereas approximately 50% of the response of noradrenaline-activated vessels persisted. The results of this investigation indicate that the effect of felodipine may be caused primarily by selective inhibiton of responses evoked by membrane depolarization.
JBB, an open access journal
J Bioequiv Availab ISSN: 0975-0851 JBB, an open access journal Volume 8(4): 153-166 (2016)-166
A validated, stability-indicating HPLC method for the determination of Felodipine and its related substances
  • L Hu
  • Q Hu
  • G Na
Hu L, Hu Q, Na G (2013) A validated, stability-indicating HPLC method for the determination of Felodipine and its related substances. International Journal of Pharmaceutical Sciences and Research 4:3369-3374.