Quetiapine Research Articles

Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment.

The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC) of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability. QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in bioavailability would result in minimization of side effects. The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential lymphatic uptake. Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables during optimization by Central Composite Design. The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of - 19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical, smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cycloheximide untreated rats' group of QF-NLC by 2.43 times as compared to cycloheximide treated group, confirmed lymphatic absorption of QF- NLC. The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.

Assessment of the biotic and abiotic elimination processes of five micropollutants during cultivation of the green microalgae Acutodesmus obliquus

The elimination by photolysis, microalgae and sorption of five persistent micropollutants Sulfamethoxazole (SMX), Ciprofloxacin (CIP), Quetiapine (QUT), Gabapentin (GAB) and 2-Phenyl-5-benzimidazolesulfonic acid (PBSA) was studied. Microalgae growth was not inhibited by the micropollutants. SMX, QUT, CIP were significantly eliminated during exposure with microalgae, while GAB and PBSA remained unaffected. SMX was eliminated by 43% only under optimal cultivation conditions at an elimination rate of 2.1 μg L−1 h−1. Sorption and photolysis were not involved in the elimination of SMX. QUT was eliminated by 99% with a rate of 4.6 μg L−1 h−1 during microalgae cultivation as a result of photolysis and microalgae activity. Microalgae cultivation produced a 52.8% higher elimination compared photolysis. CIP decreased by 86% at a rate of 1.78 μg L−1 h−1 which was mainly produced by photolysis with an impact of microalgae of 10%. Growth rates of the microalgae and elimination rates of the micropollutants were not correlating. While the underlying processes remained unclear, present study shows that biotic processes coupled to the growth of Acutodesmus obliquus removed most of the micropollutants under study at rates exceeding those of the abiotic removal processes.

Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats

Quercetin (QCN) is commonly used in high doses as a dietary supplement for weight loss. Psychotic patients are at greater risk of developing obesity than the general population. The present study was designed to understand the impact of QCN on the exposure of quetiapine (QTE), an anti-psychotic drug with narrow therapeutic index and brain penetrating capability. The content of QTE in rat plasma was analyzed through liquid chromatography–tandem mass spectrometry. The results showed a significant (p < 0.05) increase in exposure of QTE (peroral dosed) in the animals pre-treated with QCN as compared to the control group. All the animals pre-treated with QCN, succumbed to death within 3–5 min of intravenous dosing of QTE (1 mg/kg). The studies in rat liver S9 fraction indicated that QCN could increase the metabolic stability of QTE by inhibiting the activity of CYP enzymes. The brain to plasma ratio of QTE increased upon QCN pre-treatment (2.6 vs 7.7), which could be attributed to P-glycoprotein inhibition at the blood–brain barrier by QCN. The current set of studies indicated that serious herb–drug interaction between QCN and QTE might occur when they are co-administered. Caution is advised for concomitant use of QCN rich dietary supplements with QTE.

Successive Stability Indicating Spectrophotometric Technique for Simultaneous Determination of Quetiapine Fumarate and its Three Major Related Compounds

Background: Quetiapine Fumarate (QTF) is an atypical antipsychotic drug used to treat mental disorders as depression and schizophrenia. The analysis of the dug in the presence of its precursors, degradants and impurities without interference represents a challenge for the analysts. The regulatory requirements recommended by ICH stated that the impurities above or equal to 0.1% must be identified, characterized and determined. The aim of this work was to introduce three smart and selective spectrophotometric methods that could resolve the complete overlapping of QTF drug with its three related compounds; namely lactam (LAC), N-oxide (OXD) and des-ethanol (DES) without prior separation or extraction step. Methods: So far there is no spectrophotometric method reported in the literature for the analysis of QTF drug with its three related compounds without interference. The First derivative zero crossing (1D-ZC), Spectrum subtraction (SS), and Simultaneous derivative ratio (S1DD) are well-developed methods used for determination and resolution of multicomponent mixtures. While Ratio difference isosbestic point method is a new method that needs two isoabsorptive points for its application and was successfully adopted for simultaneous estimation of ternary mixtures. Results: The linearity range was found in the range of (6-50 μg/mL) for Quetiapine fumarate, (6-110 μg/mL) for lactam, (4-28 μg/mL) for N-oxide and (6-32 μg/mL) for Des-ethanol. The method validation was performed according to ICH guidelines. The results were statistically compared with a reported HPLC method and no significant difference was obtained. Conclusion: The presented spectrophotometric technique highlighted the significance of different tools such as normalized spectra and isoabsorptive points, especially when combined together for the determination and resolution of complex quaternary mixtures as that of QTF and its three major impurities. The proposed methods were smart, accurate and sensitive and were able to determine the four components showing sever overlap without prior separation. The proposed methods are rapid, cheap ecofriendly (green method) and didn’t require any sophisticated programs and could be easily adopted for the routine determination of complex multicomponent mixtures with minimum sample preparation.

Effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic supraoptic nucleus.

The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons. Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections. The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE). The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.

Changing the Drug Delivery System: Does It Add to Non-Compliance Ramifications Control? A Simulation Study on the Pharmacokinetics and Pharmacodynamics of Atypical Antipsychotic Drug.

This study investigates the pharmacokinetic (PK) and pharmacodynamic (PD) consequences of shifting from Quetiapine fumarate immediate-release (IR) to extended-release (XR) formulation in non-adherent schizophrenia patients. Monte-Carlo simulations using population PK and PD models were implemented to predict the time course of plasma concentration and Brief Psychiatric Rating Scale (BPRS) scores following the oral administration of 200 mg Seroquel® every 12 h and 400 mg Seroquel XR® every 24 h in patients experiencing dose delay, omission or doubling. Parameters were computed and their distributions were compared using the Kolmogorov–Smirnov test. Dose irregularities with both formulations had different effects on plasma concentration and %reduction in BPRS scores from baseline. However, the odds ratio of getting a %reduction in BPRS below 14%, or plasma concentration exceeding 500 µg/L, were comparable for adherent and non-adherent patients. Plasma therapeutic concentration after treatment cessation was maintained for <24 h in 48% and 29.6% of patients, and a steady state recovery time of <48 h was achieved in 51% and 13.4% of patients on the IR and XR formulations, respectively. Monte-Carlo simulations predict that the risks associated with the IR dose irregularities are not worsened when the XR formulation is used instead. Non-adherence events involving a single dose of either formulation do not require rescue doses.

Innovative spectrofluorometric protocol based on micro-environment improvement for determination of Quetiapine in dosage forms and rat plasma.

Quetiapine (QUT) is an atypical antipsychotic drug indicated for the treatment of schizophrenia and acute manic episodes associated with bipolar disorders. A simple, rapid, and highly sensitive micellar spectrofluorometric method has been developed and validated for quantitation of QUT in its pharmaceutical formulations with application to content uniformity test, in presence of its degradation product and in rat plasma. The proposed method was based on the enhancement of the fluorescence intensity of QUT in 2% v/v tween 80 micellar solution. The fluorescence intensity was measured at 372nm after excitation at 261nm. A linear relationship was achieved between the fluorescence intensity and the drug concentration in the range of 20-1000ng/mL with 18.5 and 6.3ng/mL as limits of quantitation and detection, respectively. The proposed method was extended to study the stability of QUT after its exposure to different forced degradation conditions such as; acidic, alkaline, oxidative, photolytic and thermal conditions according to ICH guidelines. The study revealed that QUT is stable under all the of these conditions except the oxidative one. Furthermore, the high sensitivity of the micellar method permits its application for determination of QUT in rat plasma with good percentage recovery as well as determination of Cmax.

Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate.

Background Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first-pass metabolism resulting in enhanced bioavailability.Objective The present work aimed at developing, and characterising potentially lymphatic absorbable Solid Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach.Methods Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively. A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months.Results The optimised formula derived for SLN had 270mg Precirol ATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetics (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for storage and preserving important characteristics within acceptable limits.Conclusion Development and optimisation by Quality by Design were justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

C-Fos and FosB/ΔFosB colocalizations in selected forebrain structures after olanzapine, amisulpride, aripiprazole, and quetiapine single administration in rats preconditioned by two different mild stressors sequences.

Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell). The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor - handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles. The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated. The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.

Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients

Background:Shared etiological pathways of dopamine and serotonin neurotransmission play a central role in heavy alcohol intake and exacerbation in the symptoms of depression.We investigated the treatment efficacy of Quetiapine fumarate extended release (XR) in lowering alcohol intake in alcohol use disorder (AUD) patients indicated by the shared alleviation of depression ratings and patterns of heavy drinking.Methods:Hundred and eight male and female heavy drinking AUD patients in the age range of 18 to 64 years. participated in a randomized clinical trial (RCT) to receive 12 weeks of quetiapine XR or placebo (N = 115). Participants were sub-grouped by the severity grading of depression using Montgomery-Asberg Depression Rating Scale (MADRS) (clinically relevant ⩾8 [CR], clinically non-relevant ⩽7 [CNR]) at baseline in both the groups. Drinking history and depression ratings were assessed at the patients’ visits.Results:Heavy drinking days (HDD) and total drinks (TD) were significantly fewer in CR patients at the treatment end. A true positive response in AUROC analysis supported the lowering of TD in CR patients. The number of drinking days (NDD) and average drinks per drinking day (AvgD) were lower in the CNR patients at treatment-end. Significant associations with increasing effect sizes were observed for all the heavy drinking measures (HDD, TD, NDD, and AvgD) and MADRS scores by the end of the treatment course.Conclusions:Baseline elevated depressive symptoms could likely predict the course of heavy alcohol drinking during the treatment, and efficacy outcome of a treatment. AUD patients with baseline clinically significant depression had a progressive lowering in heavy drinking markers significantly corresponding to the lowering of depression symptoms by the end of treatment with Quetiapine fumarate XR.ClinicalTrials.gov: NCT#0049862 (https://clinicaltrials.gov/ct2/show/NCT00498628?term=litten&draw=2&rank=3)

Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Selective Potentiometric Sensors for the Determination of Quetiapine Fumarate in Pharmaceuticals and Spiked Human Urine

Selective Potentiometric Sensors for the Determination of Quetiapine Fumarate in Pharmaceuticals and Spiked Human Urine

Formulation and Evaluation of Gastroretentive Drug Delivery Systems of Quetiapine Fumarate

Formulation and Evaluation of Gastroretentive Drug Delivery Systems of Quetiapine Fumarate

Development and Validation of an Analytical Method for the Identification of 2-Nitrophenyl (phenyl)sulfane as Potential Genotoxic Impurity of Quetiapine Fumarate at Trace Levels by High-Performance Thin-Layer Chromatography

Genotoxic impurities can be described as impurities that can induce genetic mutations and chromosomal breaks, or that damage the genetic information within a cell, which may lead to cancer. The European Medical Agency (EMA) and the United States Food and Drug Administration (US FDA) have set a threshold of toxicological concern (TTC) of genotoxic impurities 1.5 μg per day. In a continuous effort to develop an analytical method for the estimation of genotoxic impurities in quetiapine fumarate, a sensitive, simple, and precise high-performance thin-layer chromatography method has been developed and validated for the determination of 2-nitrophenyl( phenyl)sulfane as a genotoxic impurity at trace levels. The limits of detection (LOD) for quetiapine fumarate and 2-nitrophenyl( phenyl)sulfane were found to be 5.11 and 15.5 ng per band, whereas the limits of quantification (LOQ) were observed 0.09 and 0.3 ng per band, respectively. The calibration curve for 2-nitrophenyl( phenyl)sulfane was linear over the concentration range of 10 to 50 ng per band. The method was found to be specific, precise, linear, and accurate for the estimation of 2-nitrophenyl(phenyl)sulfane at trace levels in quetiapine fumarate.

Development and validation of stability indicating rp-uplc assay method for the determination of lacosamide and quetiapine fumarate in bulk and tablet dosage forms

Validation of stability indicating RP-UPLC assay method for the determination of Lacosamide and Quetiapine fumarate in pharmaceutical products. This method has showed a high degree performance in separation and quantification of Lacosamide and Quetiapine even in the presence of its impurities. The separation was quite efficient on waters acquity BEH C18 column (50 mm×2.1 mm, 1.7 μm) having used the phosphate buffer pH 2.5 and acetonitrile in the ratio of 75:25 v/v with a flow rate of 0.2 mL/min. The detection was carried out at 210 nm and the elution run time was 5.0 min. The method was linear and found to be in the range between 0.0149 μg/mL-74.71μg/mL (r2=0.9999) and 0.0148 μg/mL-74.67 μg/mL (r2=0.9999) for Lacosamide and Quetiapine respectively. The limit of detection 0.0149μg/mL, 0.0148μg/mL and quantification 0.031 μg/mL, 0.030 μg/mL for Lacosamide and Quetiapine were determined respectively. The precision result of the method ‘% RSD’ is less than 0.70 % and the recovery % of Lacosamide, Quetiapine is between 99.1 and 99.9. When the drug is subjected to different stress conditions, the consequential degradation products obtained could not interfere with Lacosamide and Quetiapine during the determination.

Investigative Study on Impact of Solid: Liquid Lipid Ratio and Stabilizer Amount on Some Characteristics of Nanostructure Lipid Carriers of Quetiapine Fumarate

Aim: Nanostrucured Lipid Carriers (NLCs) are the 2nd generation of Solid Lipid Nanoparticles (SLNs) designed to overcome limitations of SLNs. Their characteristics can be modulated by variations in formulation and process variables. The present study was aimed at investigating the influence of formulation variables, solid: liquid lipid ratio and stabilizer amount on some important characteristics of Quetiapine Fumarate Nanostructured Lipid Carriers (QF-NLC) like percent Entrapment Efficiency (%EE), Particle Size (PS), Polydispersity Index (PDI) and Zeta Potential (ZP). Methods and Materials: The study was carried out by varying the ratio of solid:liquid lipid and stabilizer amount sequentially in two sets of experiments and studying their impact on the selected characteristics of QF-NLC. Hot emulsification followed by ultrasonication was the method of preparation. Precirol ATO5, oleic acid and Phospholipon 90G (P90G) were selected as the solid lipid, liquid lipid and stabilizer respectively. Results: On varying the solid: liquid lipid ratios in the first set of experiments, %EE, PS and ZP ranged from 65.05-75.52%, 281.5-150.4nm and -16.4- -21.4mV respectively showing that decrease in the ratio was related to %EE and ZP inversely and to PS and PDI directly. Increase in the amount of P90G in the second set of experiments showed %EE to be affected positively and PS and PDI negatively. ZP was less sensitive to changes in P90G. Conclusion: From the study it can be concluded that by varying the chosen formulation variables a QF-NLC formulation with desired characteristics can be formulated for the chosen objective.

Electrochemical determination of atypical antipsychotic drug quetiapine using nano-molecularly imprinted polymer modified carbon paste electrode

In this research, the advantages of molecularly imprinted polymer (MIP) materials have been used to develop a new electrochemical sensor for determination of quetiapine (QTP) drug. MIP nanoparticles were synthesized by precipitation polymerization method and used as QTP recognition elements in the composition of modified carbon paste electrode (CPE) for selective and sensitive assay of this drug. Cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were used for electrochemical analysis. Some parameters affecting the sensor performance were optimized and under optimal conditions, the proposed sensor showed linear responses with QTP concentration in the range of 1.6 × 10−8 to 2.5 × 10−6 M (R2 = 0.9964). The limits of detection (LOD) and quantification (LOQ) were calculated 5.04 × 10−9 M and 1.68 × 10−8 M respectively. Also, the amounts of %RSD for evaluation of repeatability and reproducibility of the proposed sensors were respectively obtained 2.19 and 3.02%. The method was successfully applied to determination of QTP in its pharmaceutical formulation and human urine samples.

Product transfer from lab-scale to pilot-scale of quetiapine fumarate orodispersible films using quality by design approach

In this study, transfer from lab-scale non-continuous production to pilot-scale continuous production of orodispersible films was provided using solvent casting method under the framework of quality by design. Non-continuous production was carried out with petri dishes and continuous production was carried out with a coating machine. Films containing hydroxypropyl methylcellulose E5 as film forming polymer, polyethylene glycol 400 and propylene glycol as plasticizers, quetiapine fumarate as drug were formulated. Viscosity of the polymer dispersions, weight, thickness and disintegration time of the films were compared for the transfer of production. pH, moisture content, mechanical properties, folding endurance, uniformity of dosage units, dissolution, stability studies were also performed in pilot-scale orodispersible films. Finally, cytotoxicity studies were performed to determine cell viability. The study showed the possibility of producing F2-p-65/70 (pilot-scale film formulation containing 10 mg propylene glycol, dried at 65 °C and 70 °C) and F4-p-65/70 (pilot-scale film formulation containing 15 mg propylene glycol, dried at 65 °C and 70 °C), as the most suitable for further studies. Thus, a promising improvement has been achieved for schizophrenic patients by the production of quetiapine fumarate loaded orodispersible films and the process of scale-up in films has been demonstrated.

Development and pharmacokinetics evaluation of quetiapine fumarate sustained-release tablets based on hydrophilic matrix

Formulation with sustained release profiles is highly desired for the treatment of bipolar disorder (BD) to improve patient compliance by avoiding frequent dosing and stabilizing drug plasma concentration. For this purpose, quetiapine fumarate hydrophilic matrix tablets (QFHMTs) was designed and developed in this study. This hydrophilic matrix was accomplished by the blended polymer systems composed of HPMC K100LV and HPMC K4M to achieve appropriate hydration rate and gel strength for sustained-release of QF. QFHMTs was optimized by single factor experiment and orthogonal test, and the reproducibility test was confirmed. The optimized QFHMTs showed 24-h sustained release profile. Moreover, the results of stress testing, accelerated and long-term testing manifested its excellent storage stability with an Opadry200 coat. QFHMTs was proved promising for the treatment of BD.

Green chromatographic methods for simultaneous determination of quetiapine and the co-administrated paroxetine in rat plasma with application to pharmacokinetic study

Newly established green TLC-densitometric and RP-HPLC methods were developed and validated for simultaneous determination of quetiapine (QUT) (an antipsychotic drug) and the co-administrated drug, paroxetine (PAR) (an antidepressant drug). Both drugs are widely prescribed for treatment of bipolar depression. The proposed TLC-densitometric method was based on separation of the studied components and the internal standard (vincamine (VINC)) using a developed system of ethyl acetate: ethanol: ammonia solution 33% (8: 2:0.05, by volume) on TLC silica gel 60 F254 plates and scanning at 240 nm. Linear relationships were obtained over a concentration range of 150–3000 ng/band for both using 1000 ng/mL of vincamine (VINC) as an internal standard. On the other hand, the proposed RP-HPLC method depended on separation of the studied components and the internal standard (vincamine) using a mixture of methanol: 0.05 M KH2PO4 (pH 4.3) (70:30, v/v) on XTerra® HPLC RP C18 column (4.6 mm × 250 mm, 5 µm) at a flow rate of 1 mL/min, and UV detection at 240 nm. Linearity was achieved on the concentration range of 150–5000 ng/mL for both using 1000 ng/mL of VINC as an internal standard. The greenness profile of the developed methods was assessed and compared with reported HPLC method using the analytical Eco-Scale as an assessment tool. The proposed methods were found to be greener than the reported method. Furthermore, the developed methods were validated following FDA guidelines and all parameters met the acceptance criteria. In addition, they were successfully used to study the pharmacokinetic parameters of both QUT and PAR after their co-administration in rats and results showed that both drugs affected the pharmacokinetic parameters of each other when administrated together. The developed methods can be used for further monitoring of the studied drugs in patients.