Lurasidone Research Articles

A fast and economical flow injection-fluorometric technique has been employed for the estimation of lurasidone (LUR) in pharmaceutical formulations and biological fluids. LUR natively fluoresces due to the presence of the benzothiazole ring in its chemical composition. The assay relies on detecting the intense native fluorescence of LUR at 398 nm after excitation at 316 nm. Phosphate buffer (pH: 4.5, 10 mM): Acetonitrile (30:70 v/v) was used as the carrier solution, and the flow rate was 0.5 mL min-1. Based on peak area, the calibration graph was linear throughout the range of 30-800 ng mL-1 of LUR with a correlation coefficient (r) of 0.9999. The limit of quantitation was 21.7 ng mL-1, while the limit of detection was 7.16 ng mL-1. The approach was applied to quantify LUR in pharmaceuticals and human plasma. The approach was assessed in accordance with ICH specifications. There were no excipient-related interferences during the application of the analyses.

Abstract Purpose Lurasidone hydrochloride (HCl) is an atypical antipsychotic used for bipolar depression. However, as a Biopharmaceutics Classification System (BCS) Class II drug, it has low solubility, leading to limited oral bioavailability. This study aimed to enhance the dissolution rate and bioavailability of lurasidone HCl by modifying its crystalline structure through co-processing with weak acidic compounds, namely citric acid and nicotinic acid. Methods Lurasidone HCl was co-processed with excipients using the wet co-grinding technique at different molar ratios. The prepared formulations were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) to investigate solid-state modifications. Dissolution studies were conducted to evaluate the impact of co-processing on drug release. The optimum ratio for each co-former was selected for in vivo assessment of oral bioavailability using the forced swim test (FST) to evaluate antidepressant activity. Results DSC, FTIR, and XRD confirmed the formation of a lurasidone HCl-citric acid co-crystal, while a eutectic mixture was proposed for lurasidone HCl-nicotinic acid formulations. Dissolution studies demonstrated a two-fold increase in dissolution efficiency compared to unprocessed lurasidone HCl. FST evaluation showed increased immobility durations of 1.7-fold for raw lurasidone HCl, 2.9-fold for the marketed product (Elbaluran®), 2.19-fold for the co-crystal formulation (F3), and 3.08-fold for the eutectic mixture formulation (F7), respectively. Conclusion Citric acid and nicotinic acid effectively enhanced lurasidone HCl dissolution and bioavailability through co-crystallization and eutectic formation, respectively, offering a promising approach for optimizing its therapeutic efficacy.

In vitro, in vivo and in silico assessment of bioresorbable PLGA-PEG-PLGA based thermosensitive hydrogel mediated 30-days delivery of Lurasidone HCl for schizophrenia.

Nitrosamine impurities, such as N-nitroso diethylamine (NDEA), N-nitroso dimethylamine (NDMA), and 1-nitroso piperazine (1-NP), have raised serious health concerns due to their carcinogenic and mutagenic properties. The pharmaceutical industry faces increasing regulatory pressure to monitor these compounds at trace levels. This study addresses the need for a robust analytical method to ensure the safety of lurasidone hydrochloride (LUR), an antipsychotic drug. A sensitive and specific LC-MS/MS method was developed using atmospheric pressure chemical ionization (APCI) in positive mode and operated in multiple reaction monitoring (MRM). Chromatographic separation was performed on a Sapphirus C18 HP-classic column under gradient elution, with 0.1% formic acid in water and methanol as the mobile phase. Detection was carried out using an Agilent 6470B triple-quadrupole mass spectrometer. The method demonstrated excellent linearity (regression coefficient > 0.999) across a range extending to 200% of the specified limit. Limits of detection and quantitation were suitable for trace-level analysis. Accuracy was confirmed through recovery studies, with results ranging between 80 and 120%. The method met ICH Q2 (R2) validation criteria, ensuring reliability for regulatory use. The developed APCI-LC-MS/MS method provides accurate and reproducible quantification of NDEA, NDMA, and 1-NP in lurasidone hydrochloride. Its sensitivity and compliance with regulatory standards make it suitable for routine quality control and stability testing of nitrosamine impurities in lurasidone hydrochloride drug substance.

To define the bioequivalence (BE) of two orally administered film coated tablets containing 40 mg lurasidone hydrochloride. A single-dose, open-label, randomized two-way crossover trial was conducted under fed conditions, with a washout period of at least one week. Blood samples were drawn over a period of 72 h and plasma concentrations were analysed using a Liquid Chromatography tandem Mass Spectrometry (LC–MS/MS) method. The Pharmacokinetic (PK) parameters were calculated using Phoenix WinNonlin software, based on non-compartmental analysis. The two one-sided hypothesis at the α = 0.05 level of significance was tested by constructing the 90% confidence interval of two one-sided t-tests for the geometric mean ratios test versus reference preparation with analysis of variance (ANOVA). After oral administration of 40 mg lurasidone hydrochloride under fed conditions, the mean area under the curve (AUCt, AUC∞) and maximum plasma concentrations (Cmax) were 175 ng/mL*h; 184 ng/mL*h and 60 ng/mL, respectively for the test product and 185 ng/mL*h; 198 ng/mL*h and 59 ng/mL respectively for the reference product. 90% Confidence Intervals (CI) for all PK parameters were within the acceptance range of 80.00–125.00%. BE was demonstrated between the generic product and the innovator product in healthy Caucasian male subjects. No clinically meaningful differences in safety or tolerability were observed.

Real-world Effectiveness and Tolerability of Lurasidone in Outpatients with Bipolar DisorderII- A 24week retrospective study (RETLO-BDIIstudy).

Formulation and Characterization of Chitosan Based Oral Nanoparticles of Poorly Water-Soluble Drug Lurasidone Hydrochloride

Mental illness is the leading cause of the global burden of non-fatal disease. Lurasidone hydrochloride (LSD) is an important antipsychotic drug, but has poor water solubility and low oral bioavailability (9-19%). Additionally, LSD exhibits twice the positive food effect, meaning that patients need to consume 350 kcal when taking the medication, which leads to reduced adherence. In this study, we developed oral LSD liposome enteric-coated capsules to eliminate the food effect and improve the oral bioavailability of LSD. Firstly, liposomes were prepared by cethanocl injection cmethod, and their morphology, particle size, polydispersity index, encapsulation efficiency, drug loading capacity, stability and in vitro release were characterized. Subsequently, the mucous permeability and transepithelial transport capacity of p-R8-DOCA-Lipos in intestinal epithelial cells were investigated, and the in vivo pharmacokinetics and biosafety of LSD liposome enteric-coated capsules were further studied. p-R8-DOCA-Lipos had uniform morphology (particle size~112 nm), high encapsulation efficiency and drug loading capacity, and good stability in SIF. Cellular studies have shown that pHPMA gradually dissolved as it penetrated the mucus layer, and exposed R8-DOCA-Lipos facilitated cellular uptake. The cellular uptake and cumulative transepithelial transport of p-R8-DOCA-Lipos were 4.96 and 3.80 times higher than those in the solution group, respectively. The endocytosis of p-R8-DOCA-Lipos were mainly mediated by clathrin, caveolin and ASBT. Intracellular tracing showed that p-R8-DOCA-Lipos could achieve lysosomal escape, and ER and GA pathways were involved in their intracellular transport. In vivo pharmacokinetic studies have shown that AUC0-t of p-R8-DOCA-Lipos under fasted and fed conditions were similar to that of LSD suspension under fed conditions, which reduced the food effect of LSD and improved patient compliance. Finally, they had good biosafety after continuous oral administration. Therefore, p-R8-DOCA-Lipos may be a promising strategy for overcoming multiple gastrointestinal barriers to improve oral absorption of LSD.

This research aims to develop nanostructured lipid carriers containing Lurasidone hydrochloride (LH) with Quality by Design (QbD) methodology to enhance its bioavailability, given LH's low water solubility (0.224 mg/ml) and bioavailability (9-19%). The optimized LH-NLC formulation contains Glyceryl monostearate (GMS) as solid lipid, Caproyl 90 as liquid lipid and co-surfactant, and Tween 80 as surfactant. The hot emulsification method was used to formulate the LH-NLC using a three-factor, three-level Box-Behnken design (BBD)for ascertaining functional relationships between particle size and entrapment efficiency (EE). Particle size, polydispersity index (PDI), zeta potential, surface morphology, percentage EE, and in vitro and ex-vivo release were assessed. Wistar rats were used to estimate plasma drug concentration after LH-NLC administration. The developed formulation exhibited a particle size of 190.98 ± 4.72 nm, zeta potential of + 17.47 mV, and encapsulation efficiency of 94 ± 1.26% w/w. LH-NLCs showed a drug release rate of 95.37% within 24 hours. Intranasal administration of LH-NLCs resulted in 5.16 times higher bioavailability compared to intranasally administered lurasidone. The study successfully applied QbD methodology to develop NLCs for LH with enhanced bioavailability, demonstrating improved drug entrapment and delivery efficacy for treating psychosis.

The research aims to develop and validate a stability-indicating reverse phase high-performance liquid chromatography (RP-HPLC) method for Lurasidone hydrochloride, an antipsychotic drug derived from benzisothiazole derivatives. A Binary Gradient HPLC System with a PDA detector, C18 column (4.6 x 100 mm, 2.5 mm), and a Shimadzu 8040 series triple quadrupole mass analyzer with an electron spray ionizer was used for the LC-MS/MS analysis. The method was linear in the concentration range of 10-50 μg/mL with a correlation coefficient (r 2) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 0.091 μg/mL and 0.275 μg/mL, respectively. Validation included accuracy, percentage recovery, robustness, system suitability, and interday and intraday precision. Forced degradation studies were conducted in acid, alkali, oxidative, neutral, and photolytic conditions after 1, 2, and 6 hours, and in oxidative conditions for 24 hours. Degraded products were evaluated on LC-MS (100 m/z to 550 m/z). Lurasidone was more susceptible to alkali hydrolysis, with fragmentation peaks at 109, 166, 220, and 317 m/z. and possible fragmentation pattern was also evaluated. This method is used for routine quality control analysis as a stability-indicating method of Lurasidone hydrochloride in pharmaceuticals, and the LC-MS data is used for evaluating stability and identifying drug intermediates.

Development studies on the orodispersible freeze-dried platforms for lurasidone hydrochloride - Understanding the effect of amino acid additive and lyophilization stage.

Deaggregation of micronized insoluble drugs by incorporating mannitol form α.

Advanced stability-indicating RP-HPLC method for the quantification of lurasidone hydrochloride in bulk and PLGA-based in situ implant formulation

The potential of supramolecular synthon to develop coamorphous systems with tailored physical stability: Mechanistic insights integrating kinetics and thermodynamics

Robust analytical method for the enantiomeric separation of lurasidone hydrochloride: Integrating analytical quality by design and green chemistry principles

Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317). This is a retrospective cohort study. Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively. The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.

Specific surface area of mannitol rather than particle size dominant the dissolution rate of poorly water-soluble drug tablets: A study of binary mixture

Fabrication of PF-127 Based Niosomal In Situ Gel for Intranasal Delivery of Lurasidone Hydrochloride and Optimization by Using 32 Factorial Design

This study developed potentiometric sensors for detecting lurasidone HCl (LSH), a vital drug for treating schizophrenia and bipolar I disorder, in pharmaceutical formulations and biological samples. The sensors are based on screen-printed electrodes (SPE) modified with a molecularly imprinted polymer (MIP) synthesized using lurasidone as a template, 1-vinyl-2-pyrrolidine (VP) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, and benzoyl peroxide as an initiator. The SPE was further modified with a conductive polyaniline (PANI) film and a polyvinyl chloride (PVC) layer containing MIP as an ionophore and multiwalled carbon nanotubes (MWCNT) as a transducing material along with 2-nitrophenyl octyl ether (2-NPOE) as plasticizer. This configuration resulted in a sensor with a sensitive response and high selectivity for LSH. The electrochemical evaluation showed a Nernstian response slope of 57.3 ± 0.5 mV decade-1 in a concentration range of 10-4 to 10-8 M, with a detection limit of 10 nM and a response time of 2-3 minutes in Tris buffer (pH = 7.0). The optimized sensor possessed significantly enhanced accuracy, providing a cost-effective alternative to traditional methods. The accuracy, selectivity, precision, stability, and sensitivity of these potentiometric sensors make them valuable for detecting LSH in urine samples spiked with the pharmaceutical formulation Serodopamoun®.

This study aimed to develop a nanoparticle drug delivery system using poly (lactic-co-glycolic acid) (PLGA) for enhancing the therapeutic efficacy of lurasidone hydrochloride (LH) in treatment of schizophrenia through intramuscular injection. LH-loaded PLGA nanoparticles (LH-PNPs) were prepared using the nanoprecipitation technique and their physicochemical characteristics were assessed. Particle size (PS), zeta potential, morphology, % encapsulation efficiency, % drug loading, drug content, and solid-state properties were analyzed. Stability, in vitro release, and in vivo pharmacokinetic studies were conducted to evaluate the therapeutic efficacy of the developed LH-PNPs. The optimized batch of LH-PNPs exhibited a narrow and uniform PS distribution before and after lyophilization, with sizes of 112.7 ± 1.8 nm and 115.0 ± 1.3 nm, respectively, and a low polydispersity index. The PNPs showed high drug entrapment efficiency, drug loading, and drug content uniformity. Solid-state characterization indicated good stability and compatibility, with a nonamorphous state. The drug release profile demonstrated sustained release behavior. Intramuscular administration of LH-PNPs in rats resulted in a significantly prolonged mean residence time compared with the drug suspension. These findings highlight that intramuscular delivery of the LH-PNP formulation is a promising approach for enhancing the therapeutic efficacy of LH in treatment of schizophrenia.