Levocetirizine Research Articles

Formulation and Evaluation of Levocetirizine Gastro-Retentive Floating Tablets

Formulation and Evaluation of Levocetirizine Gastro-Retentive Floating Tablets

Simultaneous bioanalysis and pharmacokinetic interaction study of acebrophylline, levocetirizine and pranlukast in Sprague–Dawley rats

The combination of acebrophylline (ABP), levocetirizine (LCZ) and pranlukast (PRN) is used to treat allergic rhinitis, asthma, hay-fever and other conditions where patients experience difficulty in breathing. This study was carried out with the aim of developing and validating a reverse-phase high-performance liquid chromatographic bioanalytical method to simultaneously quantitate ABP, LCZ and PRN in rat plasma. The objective also includes determination of the pharmacokinetic interaction of these three drugs after administration via the oral route after individual and combination treatment in rat. Optimum resolution between the analytes was observed with a C18 Kinetex column (250 mm × 4.6 mm × 5 μm). The chromatography was performed in a gradient elution mode with a 1 mL/min flow rate. The calibration curves were linear over the concentration range of 100-1600 ng/mL. The intra- and inter-day precision and accuracy were found to be within acceptable limits as specified in US Food and Drug Administration guideline for bioanalytical method validation. The analytes were stable on the bench-top (8 h), after three freeze-thaw cycles, in the autosampler (8 h) and as a dry extract (-80°C for 48 h). The statistical results of the pharmacokinetic study in Sprague-Dawley rats showed a significant change in pharmacokinetic parameters for PRN upon co-administration of the three drugs.

Simultaneous determination of levocetirizine dihydrochloride and montelukast sodium in human plasma by LC–MS/MS: development, validation, and application to a human pharmacokinetic study

Objectives A simple, rapid, selective, and sensitive high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of levocetirizine dihydrochloride and montelukast sodium in human plasma using fexofenadine hydrochloride as an internal standard. Method Liquid–liquid extraction of both drugs and internal standard from plasma into ethyl acetate was used for sample preparation and analysis. Separation of both drugs and internal standard was achieved on an Inertsil ODS-3 (4.6 mm × 50 cm, dp 5 μm, particle size) column using an isocratic mobile phase of acetonitrile and 10 mM ammonium formate adjusted to pH 8 with 50 μL ammonium hydroxide in composition of 73:27 (v/v) at a flow rate of 0.7 mL/min. The LC–MS/MS was operated under the multiple reaction monitoring mode (MRM) using an electrospray ionization technique. Mass parameters were optimized to monitor transitions at m/z [M + H]+ 389.0 → 200.8 for levocetirizine dihydrochloride, m/z [M + H]+ 586.2 → 422.2 for montelukast sodium, and m/z [M + H]+ 502.2 → 466.0 for fexofenadine hydrochloride. Results The method was found to be linear in the range of 1–500 ng/mL for both drugs. The intra-day and inter-day precision were in the range of 0.96–1.92% and 1.03–1.55%, respectively. Matrix effect was acceptable with %RSD < 15. Conclusion The proposed method was validated and successfully applied for a pharmacokinetic study of both drugs in human plasma after oral administration of their pharmaceutical preparation.

Effect of levocetirizine hydrochloride on the growth of human dermal papilla cells: a preliminary study

Objective To preliminarily evaluate the effect of levocetirizine hydrochloride at different concentrations on the growth of in vitro cultured human dermal papilla cells, and to explore its mechanism. Methods Human dermal papilla cells were divided into several groups to be cultured with Dulbecco′s modified eagle medium (DMEM) containing 0 (control group) , 1, 10, 100, 1 000, 10 000 μg/L levocetirizine hydrochloride respectively for 48 hours. Immunofluorescence staining was performed to observe the growth of the dermal papilla cells, and methyl thiazolyl tetrazolium (MTT) assay to evaluate the proliferative activity of the dermal papilla cells. Real-time fluorescence-based quantitative PCR was conducted to measure the mRNA expression of cyclooxygenase 2 (COX-2) , prostaglandin D2 synthase (PTGDS) , prostaglandin E2 (PGE2) , prostaglandin F2alpha (PGF2α) , G protein-coupled receptor 44 (GPR44) , protein kinase B (AKT) and glycogen synthase kinase 3β (GSK3β) , and Western blot analysis to determine the protein expression of PTGDS. After 24-hour culture with DMEM containing levocetirizine hydrochloride at different concentrations, enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of prostaglandin D2 (PGD2) and PGD2R receptor in the culture supernatant of the human dermal papilla cells. Statistical analysis was carried out with SPSS17.0 software using one-way analysis of variance for the comparison of the above indices among the groups, and least significant difference (LSD) -t test for multiple comparisons. Results Immunofluorescence staining showed that human dermal papilla cells grew well and reached over 90% confluence in the 100 μg/L levocetirizine hydrochloride group. MTT assay revealed that there were significant differences in the proliferation rate among all the groups (F=42.22, P 0.05) . The 100 μg/L levocetirizine hydrochloride group showed significantly decreased mRNA expression of COX-2, PTGDS and GPR44 (0.84 ± 0.08, 0.81 ± 0.10 and 0.85 ± 0.09 respectively) compared with the control group (t=1.97, 2.17 and 2.66 respectively, all P < 0.05) , but significantly increased mRNA expression of PGF2α and AKT (1.96 ± 0.25 and 1.74 ± 0.32 respectively) compared with the control group (t=3.66, 7.32 respectively, both P < 0.05) . Moreover, the protein expression of PTGDS, PGD2 and PGD2R significantly differed among these groups (all P < 0.05) , and was significantly lower in the 100 μg/L levocetirizine hydrochloride group than in the control group (P < 0.05) . Conclusion Levocetirizine hydrochloride can promote the in vitro growth of human dermal papilla cells, likely by inhibiting the PGD2-GPR44 pathway and activating the AKT signal pathway. Key words: Cetirizine; Prostaglandins; Alopecia; Receptors, G-protein-coupled; Dermal papilla cells

Prediction of drug-polymer interactions in binary mixtures using energy balance supported by inverse gas chromatography

Surface energy is extensively adopted to predict the surface properties of materials nowadays. Our study was aimed at utilizing the surface free energy measured by inverse gas chromatography to determine inter-particle interactions and to describe the overall behaviour of mixtures. The model drugs of different solubility (tadalafil, levocetirizine dihydrochloride, vardenafil hydrochloride, and amlodipine besylate) and two grades of polyvinylpyrrolidone (Kollidon® 12 PF, Kollidon® VA 64) were mixed in various ratios. Investigated components were characterized using inverse gas chromatography, particle size distribution and specific surface area. We also determined the work of adhesion and cohesion between the components in the binary mixtures. Due to the formation of levocetirizine agglomerates, the effect of mixing time on both components of the surface free energy was also studied for the binary mixture with Kollidon® VA 64. The results based on the energy analysis, especially positive or negative excess surface energies in theoretical and real binary mixtures, indicate that we can predict whether the components can form the desired ordered (interactive) mixture. For this reason, we have proposed, to the best of our knowledge, different approach to predict the interactions between components and their behaviour in the binary mixtures using inverse gas chromatography in terms of the energy balance based only on the surface parameters (surface free energy, dispersive and specific surface energy). Therefore, the approach of energy balance is an innovative and comparatively simple tool for analysis and identification of interactions between components in particulate systems, which can also predict the quality of the mixing.

Comparison of therapeutic efficacy of antihistaminics and combinations of montelukast with allergic rhinitis

Allergic Rhinitis is basically a chronic disease that decreases quality of life. Antihistaminics have been used for the first time in allergic rhinitis. In the search for an alternative treatment in resistant allergic rhinitis, Montelukasts and their combinations have been used. Randomized double-blind controlled study. In our study, the effect on the quality of life of the compounds used recently be compared after 3 months of treatment. In this study, 7 groups of 40 patients, 18-65 years old were planned for each group. The number of females and males was equal in each group (20). The patients in group A and group B will be called for checks after 3 months of medical treatment in the C-D-E-F-G-H group without treatment for 3 months. The patients in Group C received 10 mg Rupatadin Fumarate tablets orally (1 * 1 single dose) before bedtime, 5 mg Levosetirizine Dihydrochloride tablets in the patients in Group D orally (1 * 1 single dose) before bedtime, 10 mg Montelukast Sodium tablets in patients in Group E Before oral (1 * 1 single dose), patients in Group F 5 mg Desloratadin + 10 mg Montelukast Sodium tablets orally (1 * 1 single dose) before bedtime, and patients in Group G Levocetirizine Dihydrochloride + 10 mg Montelukast Sodium tablet orally before bedtime (1 * 1 single dose) will be given. These treatments will continue for 3 months without interruption. The Rinokonjucivations Quality of Life Questionnaire (RQLQ) will be completed with a total of 28 questions. No significant superiority of the Rupatadine molecule to levocetirizine was detected. The score of the Montelukast areas was significantly low when compared to the Rupatadine and Levosetirizine groups. Combined Montelukastes were found to be much more effective than single antihistaminics and single montelukast. There was no difference in quality of life between the combined Montelukast. Antihistaminics are the first treatment option in patients with allergic rhinitis,In resistant cases, combinations with montelukast should be used.

Validated Derivative Spectrophotometric method for simultaneous estimation of Levocetirizine Dihydrochloride and Phenylephrine Hydrochloride from tablet formulations

Validated Derivative Spectrophotometric method for simultaneous estimation of Levocetirizine Dihydrochloride and Phenylephrine Hydrochloride from tablet formulations

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF LEVOCETIRIZINE IN BLOOD PLASMA BY USING RP-HPLC

A rapid, selective, precise and sensitive reverse phase high-performance liquid chromatography method was developed for the quantitative estimation of Levocetirizine Dihydrochloride (LD) in human plasma and pharmaceutical dosage form. Extraction of drug from plasma was done by employing optimized liquid-liquid extraction procedure. The sample was analyzed using acetonitrile: methanol: 20mM ammonium acetate buffer pH-5 (25:55:20 % v/v/v) as mobile phase. Chromatographic separation was achieved on Thermo C-18 column (4.6 x 250mm, 5μ particle size) as stationary phase using isocratic elution (at a flow rate of 1 ml/min). The peak was detected using UV-PDA detector set at 232 nm and the total time for a chromatographic separation was 8 min. The calibration curve obtained was linear (r2= 0.9998) over the concentration range of 2-10 μg/ml. Method was validated for precision, robustness and recovery. The limit of detection and limit of quantitation was 0.0057 and 0.174 µg/ml respectively. There was no significant difference between the amount of drug spiked in plasma and the amount recovered and plasma did not interfere in estimation. Thus, the proposed method is suitable for the analysis of LD in tablet dosage forms and human plasma.&#x0D; Keywords: RP-HPLC, Levocetirizine Dihydrochloride, Human plasma, Liquid-liquid extraction

Formulation and evaluation of Taste Masked Mouth Dissolving Tablet of Levocetrizine dihydrochloride by using Ion-Exchange Resin

Formulation and evaluation of Taste Masked Mouth Dissolving Tablet of Levocetrizine dihydrochloride by using Ion-Exchange Resin

Levocetirizine Dihydrochloride Loaded Chitosan Nanoparticles: Formulation and In Vitro Evaluation

Levocetirizine Dihydrochloride Loaded Chitosan Nanoparticles: Formulation and In Vitro Evaluation

Stability Indicating Hplc Method using Core Shell Stationary Phase for the Determination of Related Substances in Levocetirizine Dihydrochloride Oral Solution

Stability Indicating Hplc Method using Core Shell Stationary Phase for the Determination of Related Substances in Levocetirizine Dihydrochloride Oral Solution

RP-HPLC and UV Method Development for Simultaneous Estimation of Doxofylline, Montelukast and Levocetirizine Dihydrochloride in Pharmaceutical Dosages Form

Method has been developed and validated by using spectrophotometric and chromatographic hyphenated techniques for the simultaneous estimation of Doxofylline (DOXO), Montelukast (MONT) and Levocetirizine Dihydrochloride (LEVO) in bulk powder and in pharmaceutical formulations with a high degree of specificity, selectivity and assurances. The first Vierordt’s method was performed and absorption maxima of DOXO, MONT and LEVO at 273.3, 283.1 and 231.05 nm, respectively. The second method employs a first order derivative spectrophotometry (1D) using a crossing technique of measurement at the data point 49, where the measurement was taken at 287.93, 292.57 and 242.45 for DOXO, MONT and LEVO, respectively. Calibration graphs were established in the range of 4-24 μg/mL. RPHPLC method developed by using a C18 (150 x 250 x 4.6 mm) Agilent column and a mobile phase (Ammonia acetate Buffer: ACN) pH 3.5. The retention time of DOXO, MONT and LEVO were found to be 4.425, 7.409 and 8.558 min., respectively. Results of all three methods were found good correlation coefficients. The developed methods have been successfully applied for the determination of ternary or more bulk mixture and formulations dosages forms.

SOLID STATE COMPATIBILITY STUDIES BETWEEN MONTELUKAST SODIUM AND LEVOCETIRIZINE

Objective: The aim of this research is to evaluate montelukast (MNT)-levocetirizine (LVZ) incompatibility when they gather in one solid dosage form.Methods: Both drugs and their binary mixture (2:1) (MNT-LVZ) were subjected to the following condition: 25°C/60% RH and 40°C/75% RH for 14 weeks. Samples were withdrawn and analyzed using stability-indicating high-performance liquid chromatography (HPLC) method at time intervals (0, 1, 4, 14 weeks). Further investigations were carried out using differential scanning calorimeter (DSC), Fourier transform infrared (FTIR), and X-ray powder diffraction (XRPD)Result: On the basis of HPLC results, the degradation percentage of both drugs in binary mixtures was &lt;10% indicating no chemical interaction; this was confirmed by all FTIR results except new band 668 cm−1 appeared in the spectrum of the mixture after storing 14 weeks at 40°C/75% RH, revealing possible hydrogen bond formed in the mixture. DSC and XRPD revealed possible physical interaction including phase transformation (release the acid form of montelukast and basic form of levocetirizine and sodium chloride in the medium); this may affect dissolution rate and bioavailability.Conclusion: The results obtained from this research gave an evidence to formulate MNT and LVZ in stable fixed-dose combination for the effective treatment of allergic diseases

Design and characterization of quick dissolving film for simultaneous delivery of montelukast sodium and levocetirizine dihydrochloride

The main objective of the present investigation was to develop fast dissolving films of montelukast sodium and levocetirizine dihydrochloride using sodium starch glycolate as disintegrating agent to achieve better drug bio-availability and patient’s compliance. This combination is the most effective in the management of allergic rhinitis and asthma. The results of preformulation study indicated that drug and excipients are compatible with each other with its purest forms. The solvent casting method was used to prepare different batches of films. The prepared fast dissolving films were evaluated for physical appearance, weight uniformity, uniformity of thickness, folding endurance, surface pH, tensile strength, moisture content, disintegration time, % drug content, in-vitro dissolution studies. From the study it was found that F8 has showed maximum release of 94.40±0.48% for montelukast sodium and 95.66±0.24% for levocetirizinedihydrochloride within 225sec. Based on the results such as drug content, disintegrating time and drug release it was concluded that fast dissolving films are suitable for oral administration of montelukast sodium and levocetirizine dihydrochloride.

Stability Indicating HPLC Method Using Core Shell Stationary Phase for the Determination of Related Substances in Levocetirizine Dihydrochloride Oral Solution

Abstract: Rationale: Levocetirizine (LCZ) is a new generation antihistamine drug used for the allergic symptoms resulting from various diseases. The present research work focuses on the development of a simple and precise HPLC method for the effective separation and quantitative determination of LCZ and its impurities. Experimental: Eight potential related impurities of LCZ were separated and identified in the bulk drug as well as oral solution dosage form. The separation was achieved on a core shell stationary phase Kinetex bipheyl (250, 4.6×5 μm) column with mobile phase of sodium perchlorate in water and acetonitrile in a gradient elution. Results:The results were monitored and analytes were quantified at 230 nm. The method was validated as per ICH guidelines for specificity, linearity, precision, accuracy and robustness. The proposed method finds its application in the routine analysis of LCZ in bulk drug and various dosage forms. Key words: HPLC, Core shell, Related Substances, Levocetirizine dihydrochloride.

Observation of the effect of Bupiyichang pills combined with levocetirizine in the treatment of 56 patients with chronic urticaria

Objective To observe the effect of Bupiyichang pills combined with levocetirizine in the treatment of 56 patients with chronic urticaria, so as to provide clinical guidance and basis. Methods 118 patients with chronic urticaria were selected for our study, and after informed consent they were randomly divided into observation group and control group.The observation group were was treated by Bupiyichang pills combined with levocetirizine, and the control group were was treated by levocetirizine.When they were curingAfter treatment for 10, 20, and 30 days, the effective rates in the two groups were calculated and compared with each other.And at the day before treating and the day after treating for 20 days, the serum IgE levels in each group was detected and compared.The falling ranges between the two groups were calculated and compared. Results When they were curing treated for 10, 20, and 30 days, the effective rates in the observation group were 76.79%, 94.64%, 85.71%, respectively, which in those of the control group were 59.68%, 74.19%, 64.52%, respectively, the differences between the two groups were statistically significance significant (χ2=3.94, 9.11, 6.97, all P<0.05). At the day before treating and the day after treating for 20 days, the serum IgE levels in the observation group were (384.71±65.62)U/mL and (214.59±40.71)U/mL respectively, the difference was statistically significance significant (t=10.93, P<0.05); and the serum IgE levels in the control group were (380.25±67.81)U/mL and (256.99±53.21)U/mL respectively, the difference was statistically significancesignificant(t=9.37, P<0.05). The falling ranges in the observation group and the control group were (170.12±35.59)U/mL and (123.26±53.31)U/mL respectively, the difference was statistically significance significant between the two groups(t=7.82, P<0.05). Conclusion Bupiyichang pills combined with levocetirizine is more effective than single medication of levocetirizine. Key words: Urticaria; Reinforcing the pleen and bowel pills; Levocetirizine hydrochloride

In vitro drug interaction of levocetirizine and diclofenac: Theoretical and spectroscopic studies

Levocetirizine dihydrochloride is known to interact with some anti–inflammatory drugs. We report here a comprehensive integrated theoretical and experimental study for the in vitro drug interaction between levocetirizine dihydrochloride (LEV) and diclofenac sodium (DIC). The interaction of the two drugs was confirmed by the molecular ion peak obtained from the mass spectrum of the product. Moreover, FTIR and 1HNMR spectra of the individual drugs and their interaction product were inspected to allocate the possible sites of interaction. In addition, quantum mechanical DFT calculations were performed to search for the interaction sites and to verify the types of interactions deduced from the spectroscopic studies such as charge–transfer and non–bonding π–π interactions. It was found that the studied drugs interact with each other in aqueous solution via four types of interactions, namely, ion–pair formation, three weak hydrogen bonds, non–bonding π–π interactions and charge–transfer from DIC to LEV.

Fexofenadine and levocetirizine have equivalent effectiveness for persistent allergic rhinitis

Background: Antihistamines are used to treat allergic rhinitis. Whether better pharmacokinetic and pharmacodynamic properties confer higher clinical effectiveness is not known. Objectives: To compare the effectiveness of original fexofenadine, original levocetirizine, and locally-manufactured fexofenadine for treating persistent allergic rhinitis. Methods: Patients with persistent allergic rhinitis were enrolled during June 2010 to December 2013. Patients were allocated to receive original fexofenadine, original levocetirizine, or locally-manufactured fexofenadine forone week. Daily symptoms were self-assessed. Disease specific quality of life, allergen induced wheal and flare size, peak nasal inspiratory flow, and any adverse events were reported at one week. Results: We enrolled 69 patients. There was no significant difference in reduction of mean total symptom score between original fexofenadine, original levocetirizine, and locally manufactured fexofenadine (mean (95% CI);5.52 (3.98, 7.06), 4.32 (2.43, 6.21), 4.45 (2.51, 6.40)) respectively. Improvement in otolaryngic symptoms (P = 0.51),nonotolaryngic symptoms (P = 0.59), work and study performance (P = 0.42), exertion (P = 0.81), sleep disturbance(P = 0.76), social disturbance (P = 0.16), emotional disturbance (P = 0.66), overall general health (P = 0.55),allergen induced wheal (P = 0.44) and flare suppression (P = 0.90), and peak nasal inspiratory flow (P = 0.85)were not significantly different between the 3 groups. All groups similarly reported minor adverse events. Conclusions: There is no difference in effectiveness between fexofenadine and levocetirizine in treating persistent allergic rhinitis. Locally-manufactured and original fexofenadine similarly improve symptoms, nasal air flow, and quality of life. No major drug-related adverse events were reported. Keywords: allergic rhinitis, H1 antagonists, antihistamines, fexofenadine, levocetirizine, local-manufactured drugs,generic

Influence of Histamine H1 Receptor Antagonists on Thioredoxin Production In vitro and In vivo

Background: Thioredoxin (TRX), a 12-kDa oxidoreductase enzyme, is well known to be a redox-active protein that regulates reactive oxidative metabolism. TRX is also accepted to be a protein with anti-inflammatory effects and reported to attenuate the development of allergic airway inflammatory diseases such as allergic rhinitis (AR) and asthma. Although histamine H1 receptor antagonists are frequently used for the treatment of AR, the influence of the agents on TRX production is not well understood. In the present study, we examined the influence of fexofenadine (FEX), cetirizine (CT), and levocetirizine (LCT), which are classified into histamine H1 receptor antagonists, on TRX production in vitro and in vivo. Methods: Macrophages derived from THP-1 cells (1 × 105 cells/ml) were cultured with 50 μM H2O2 in combination with/without the agents for 24 h. Nasal secretions were obtained from patients with Japanese cedar pollen-sensitized rhinitis, who were treated with FEX or LCT for four weeks during pollen season. TRX contents in both culture supernatants and nasal secretions were examined by ELISA. Results: Addition of FEX, CT and LCT into macrophage cultures increased TRX levels in supernatants. The minimum concentration of the agents that caused significant increase was 0.3 μM for FEX, 0.4 μM for CT and LCT. Treatment of patients with FEX and LCT also caused increase in TRX levels in nasal secretions along with attenuation of clinical symptoms. Conclusion: Histamine H1 receptor antagonists may increase the ability of macrophages to produce TRX, and results in favorable modification of clinical conditions of AR.

Suppressive Activity of Histamine H1 Receptor Antagonists, Desloratadine and Levocetirizine, on the Production of Periostin from Nasal Epithelial Cells In vitro

Background: Periostin, a 90-kDa endogenous extracellular matrix protein, is well known to be involved in the development and persistence of allergic rhinitis. Although histamine H1 receptor antagonists are recommended as first choice of agents in the treatment of allergic rhinitis, the influence of the agents on periostin production is not well understood. The present study was undertaken to examine the influence of histamine H1 receptor antagonists on periostin production from nasal epithelial cells after IL-4 stimulation in vitro. Methods: Human nasal epithelial cells (HNEpC) at a concentration of 1 × 105 cells/ml were stimulated with 10.0 ng/ml IL-4 in combination with either desloratadine (DLT), loratadine (LT), levocetirizine (LCT) or cetirizine (CT). After 48 h, culture supernatants were collected and assayed for periostin levels by ELISA. The influence of LCT on transcription factor, STAT6, activation and periostin mRNA expression were also examined by ELISA and real-time RT-PCR, respectively. Results: Treatment of cells with DLT, LT, LCT and CT suppressed the ability of HNEpC to produce periostin in response to IL-4 stimulation in dose-dependent manner. The minimum concentration that caused significant suppression is 0.01 mM for DLT, 0.05 mM for LT, 0.05 mM for LCT and 0.1 mM for CT. Treatment of HNEpC with LCT at more than 0.05 mM also suppressed STAT6 activation and periostin mRNA expression induced by IL-4 stimulation. Conclusion: The present results strongly suggest that histamine H1 receptor antagonists favorably modify the clinical conditions of allergic rhinitis through the suppression of periostin production from nasal epithelial cells after IL-4 stimulation.