Bupropion Research Articles

Formulation, Optimization and Characterization of Bupropion Hydrochloride Loaded Nanostructured Lipid Carriers for Intra-Nasal Administration: An Approach to Management of Smoking Cessation

Background: Tobacco smoking is a major factor leading to cardiovascular diseases. About 48% of cardiovascular diseases occur due to cigarette smoking. Bupropion hydrochloride is a non-nicotine treatment for smoking cessation. The existing marketed formulation of bupropion has limitations, like low bioavailability and extensive first-pass metabolism. In order to boost the bioa-vailability and increase the brain biodistribution of the drug, a colloidal drug delivery system, like nanostructured lipid carriers, is employed. Methods: NLC formulation was prepared using the microemulsion technique and an optimized formula was developed using a three-level factorial design. Results: The particle size of the optimized formulation was 162 nm, the polydispersity index was 12.2%, and the zeta potential was -29.0mV. Entrapment efficiency was found to be 41.2%. SEM images show that these NLCs are spherical. In vitro drug release study was conducted, and at the end of 72 hours, 50% of the drug was released, indicating the sustained release of the drug. Histo-pathological studies were conducted using goat nasal mucosa, and results indicated the NLC formu-lation as non-toxic for intranasal administration. Conclusion: Thus, through the intra-nasal route, an increased concentration of drug can be deliv-ered to the brain via the olfactory pathway, thereby improving the therapeutic effect and exhibiting better patient compliance in smoking cessation.

Influence of Zhuanggu Guanjie Pill on Seven Cytochrome P450 Enzymes Based on Probe Cocktail and Pharmacokinetics Approaches.

The use of herbal medicines has tremendously increased over the past few decades. Case reports and controlled clinical investigations of herbal-drug interactions have been reported. Since Cytochrome P450 (CYP) enzymes play an important role in drug interactions. The evaluation of the influence of herbal medicines on the activities of CYPs is beneficial to promote scientific and rational clinical use of herbal medicines. Herein, we aimed to develop and validate a method to simultaneously quantify seven CYP cocktail probe drugs consisting of phenacetin (PNC), bupropion (BPP), losartan potassium (LK), omeprazole (OMP), dextromethorphan (DM), chlorzoxazone (CZZ) and midazolam (MDZ) and their respective metabolites in a single acquisition run and use this method to evaluate the influence of Zhuanggu Guanjie Pill (ZGGJP) on seven CYPs. A cost-effective and simple UHPLC-(±)ESI-MS/MS method for simultaneous determination of seven probe drugs and metabolites in rat plasma was developed and validated. Male and female rats were randomly divided into three groups and treated with 1.2 g/kg/d ZGGJP, 5 g/kg/d ZGGJP and 0.5% CMC-Na for 14 consecutive days. After 24 h of the last administration, all rats were administrated orally with probe drugs. The influence of ZGGJP on the CYPs was carried out by comparing the metabolic ratio (Cmax, AUC0-t) of metabolites/probe drugs in rats. The calibration curves were linear, with correlation coefficient > 0.99 for seven probe drugs and their corresponding metabolites. Intra- and inter-day precisions were not greater than 15% RSD and the accuracies were within ± 15% of nominal concentrations. The ZGGJP showed significant inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats. ZGGJP had inductive effects on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats.

Dextromethorphan/Bupropion: First Approval.

An oral, fixed-dose combination of dextromethorphan hydrobromide [an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist] and the antidepressant bupropion hydrochloride (an aminoketone and CYP2D6 inhibitor that increases dextromethorphan bioavailability) [AUVELITYTM; dextromethorphan/bupropion], is being developed by Axsome Therapeutics, Inc. for the treatment of major depressive disorder (MDD), Alzheimer's disease agitation and smoking cessation. Dextromethorphan/bupropion was approved in the USA in August 2022 for the treatment of MDD in adults. This article summarizes the milestones in the development of dextromethorphan/bupropion leading to this first approval for the treatment of adults with MDD.

Neural signaling of methamphetamine craving and seeking intensified by bupropion in the ventral tegmental area-cortico-accumbens circuitry in mice.

Previously, bupropion (BUP), a norepinephrine (NE)/dopamine (DA) transporter blocker and nicotinic acetylcholine receptors (nAChRs) antagonist, was found to intensify methamphetamine (METH) craving behaviours in mice. Intense craving causes relapse in drug dependence. This study characterized local field potential (LFP) patterns in the brain regions associated with METH-conditioned place preference (CPP) enhanced by BUP. Male Swiss albino ICR mice were implanted with LFP electrodes to the ventral tegmental area (VTA), medial prefrontal cortex (mPFC) and the nucleus accumbens core (NAcc). Animals received sessions to learn the association between injection effects (1 mg/kg METH and normal saline) with contextual environments (METH- and saline-paired compartments) during the conditioning phase. A total of 20 mg/kg BUP was given to animals before LFP, and behaviour recording in the CPP apparatus during the post-conditioning phase. The results showed that increased CPP scores and % number of entries to the METH-paired zone, as well as changes in VTA, mPFC and NAcc spectral powers and coherence among these areas, were associated with METH-CPP. Treatment with BUP increased VTA delta and gamma I, decreased mPFC alpha, increased NAcc gamma I and decreased gamma II powers. Coherence analyses revealed that BUP decreased gamma II VTA-mPFC and increased beta and gamma I VTA-NAcc connectivity. Altogether, BUP produced additional effects to that of METH-CPP alone. These findings demonstrated changes in neural circuit activities associated with METH-CPP intensified by BUP. Moreover, modulation of NE/DA systems and/or nAChRs actions in the VTA-cortico-accumbens loop might underlie METH craving and dependence.

Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development.

A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride.

A Greener Synthesis of the Antidepressant Bupropion Hydrochloride

A laboratory experiment was developed to introduce systems thinking and green chemistry concepts through the synthesis of the antidepressant and smoking cessation aid, bupropion hydrochloride. The traditional synthesis has several issues from a green chemistry perspective: it uses the toxic solvents N-methylpyrrolidinone (NMP) and dichloromethane (DCM) and other hazardous chemicals including bromine and 12 M hydrochloric acid resulting in 138 kg of waste per kg of product. A greener synthesis has been developed with suitable improvements to the traditional procedure. The reprotoxic NMP and potentially carcinogenic DCM solvents have been substituted with the green biobased solvent Cyrene and ethyl acetate, respectively, and bromine has been substituted with N-bromosuccinimide. An alternate extraction method has also been developed using 1 M hydrochloric acid and ethyl acetate rather than 12 M hydrochloric acid and diethyl ether. These changes have also reduced waste by 92 kg kg–1, and the resultant experiment is much safer to perform. As part of this laboratory experiment, students synthesize bupropion hydrochloride, and the adaptations to the traditional process are discussed and evaluated. Students are also introduced to the green metrics of atom economy, process mass intensity, and E-factor, which they use to quantify the greenness of the original and adapted procedures.

Influence of CYP2B6 Pharmacogenetics on Stereoselective Inhibition and Induction of Bupropion Metabolism by Efavirenz in Healthy Volunteers.

We investigated the acute and chronic effects of efavirenz, a widely used antiretroviral drug, and CYP2B6 genotypes on the disposition of racemic and stereoisomers of bupropion (BUP) and its active metabolites, 4-hydroxyBUP, threohydroBUP and erythrohydroBUP. The primary objective of this study was to test how multiple processes unique to the efavirenz-CYP2B6 genotype interaction influence the extent of efavirenz-mediated drug-drug interaction (DDI) with the CYP2B6 probe substrate BUP. In a three-phase, sequential, open-label study, healthy volunteers (N=53) were administered a single 100 mg oral dose of BUP alone (control phase), with a single 600 mg oral efavirenz dose (inhibition phase), and after 17-days pretreatment with efavirenz (600 mg/day) (induction phase). Compared to the control phase, we show for the first time that efavirenz significantly decreases and chronically increases the exposure of hydroxyBUP and its diastereomers, respectively, and these interactions were CYP2B6 genotype dependent. Chronic efavirenz enhances the elimination of racemic BUP and its enantiomers as well as of threo- and erythro-hydroBUP and their diastereomers, suggesting additional novel mechanisms underlying efavirenz interaction with BUP. The effects of efavirenz and genotypes were nonstereospecific. In conclusion, acute and chronic administration of efavirenz inhibits and induces CYP2B6 activity. Efavirenz-BUP interaction is complex involving time- and CYP2B6 genotype-dependent inhibition and induction of primary and secondary metabolic pathways. Our findings highlight important implications to the safety and efficacy of BUP, study design considerations for future efavirenz interactions, and individualized drug therapy based on CYP2B6 genotypes. Significance Statement The effects of acute and chronic doses of efavirenz on the disposition of racemic and stereoisomers of BUP and its active metabolites were investigated in healthy volunteers. Efavirenz causes an acute inhibition, but chronic induction of CYP2B6 in a genotype dependent manner. Chronic efavirenz induces BUP reduction and the elimination of BUP active metabolites. Efavirenz's effects were non-stereospecific. These data reveal novel mechanisms underlying efavirenz DDI with BUP and provide important insights into time- and CYP2B6 genotype dependent DDIs.

0858 Under reporting of Apnea Hypopnea Index (AHI) in patients with predominant REM sleep disordered breathing on antidepressants

Abstract Introduction The prevalence of Rapid Eye Movement (REM) related Sleep Disordered Breathing (SDB) ranges from 13.5% to 36.7% in patients suspicious to have SDB.1 It is reported that patients with REM related SDB often have associated depression and are commonly on anti-depressants.2 Antidepressants suppress overall REM sleep duration. Significant sleep disordered breathing is known to occur during REM sleep. These patients commonly present with excessive daytime sleepiness and fatigue. Obstructive sleep apnea (OSA) diagnosis is often missed in these patients secondary to REM sleep suppression and subsequent underreporting of AHI.1. Conwell W, Patel B etal 2012 PMID: 21614575. 2. Geckil AA, Ermis H. 2020 PMID: 30949927. Report of Cases: Case 1 is a 53-year-old obese white female with stable depression on citalopram 20mg presented with witnessed loud snoring and apneas, sleep onset and maintenance insomnia, daytime fatigue and hypersomnolence. Her Epworth Sleep Score (ESS) was 13/24. Her in lab baseline polysomnogram demonstrated overall AHI 3.8/hour and REM only AHI 24.3/hour. To further explore her persistent daytime sleepiness a Mean Sleep Latency Test (MSLT) was ordered. Citalopram was held 2 weeks prior to MSLT. In the PSG her overall AHI increased to 7.6/hour diagnosing her with mild OSA. PAP therapy was initiated that improved patients nocturnal sleep, daytime fatigue and hypersomnolence. Case 2 is a 54-year-old overweight white female with past medical history of chronic stable depression on Wellbutrin SR 100 mg daily presented with significant day time fatigue and hypersomnolence (ESS 15/24). Her baseline PSG reported AHI 1.7/hour with REM only AHI 10.7/hour. However due to persistent excessive daytime sleepiness MSLT was ordered. Her Wellbutrin was held 2 weeks prior to testing. Her overnight PSG demonstrated increase in her AHI to 7.9/hour and REM AHI to 34.2/hour. Mild obstructive sleep apnea was diagnosed, and PAP therapy was initiated that improved her hypersomnolence. Conclusion These cases illustrate that antidepressants likely mask obstructive sleep apnea by suppressing REM sleep. Given the underreported AHI in patients with REM SDB who are on anti-depressants it may be prudent to hold anti-depressants for 2 weeks to establish an accurate diagnosis of sleep apnea. Support (If Any)

Stereoselective Metabolism of Bupropion to Active Metabolites in Cellular Fractions of Human Liver and Intestine.

Striking stereoselective disposition of the antidepressant and smoking cessation aid bupropion (BUP) and its active metabolites observed clinically influence patients' response to BUP therapy and its clinically important drug-drug interactions (DDI) with CYP2D6 substrates. However, understanding of the biochemical mechanisms responsible is incomplete. This study comprehensively examined hepatic and extrahepatic stereoselective metabolism of BUP in vitro Racemic-, R-, and S-BUP were incubated separately with pooled cellular fractions of human liver [microsomes (HLMs), S9 fractions (HLS9s), and cytosols (HLCs)] and intestinal [microsomes (HIMs), S9 fractions (HIS9s), and cytosols (HICs)] and cofactors. Formations of diastereomers of 4-hydroxyBUP (OHBUP), threohydroBUP (THBUP), and erythrohydroBUP (EHBUP) were quantified using a novel chiral ultra-high performance liquid chromatography/tandem mass spectrometry method. Racemic BUP (but not R- or S-BUP) was found suitable to determine stereoselective metabolism of BUP; both enantiomers showed complete racemization. Compared with that of RR-THBUP, the in vitro intrinsic clearance (Clint) for the formation of SS-THBUP was 42-, 19-, and 8.3-fold higher in HLMs, HLS9 fractions, and HLCs, respectively; Clint for the formation of SS-OHBUP and RS-EHBUP was also higher (2.7- to 3.9-fold) than their R-derived counterparts. In cellular fractions of human intestine, ≥ 95% of total reduction was accounted by the formation of RR-THBUP. Ours is the first to demonstrate marked stereoselective reduction of BUP in HLCs, HIMs, HIS9 fractions, and HICs, providing the first evidence for tissue- and cellular fraction-dependent stereoselective metabolism of BUP. These data may serve as the first critical step toward understanding factors dictating BUP's stereoselective disposition, effects, and DDI risks. SIGNIFICANCE STATEMENT: This work provides a deeper insight into bupropion (BUP) stereoselective oxidation and reduction to active metabolites in cellular fractions of human liver and intestine tissues. The results demonstrate tissue- and cellular fraction-dependent stereospecific metabolism of BUP. These data may improve prediction of BUP stereoselective disposition and understanding of BUP's effects and CYP2D6-dependent drug-drug interaction in vivo.

Synthesis of non-active electrode (TiO2/GO/Ag) for the photo-electro-Fenton oxidation of micropollutants in wastewater

Heterogeneous photo-electro-Fenton oxidation (hPEF) is known to be a robust technique, which can be employed for promoting organic degradation. This paper describes an environmentally friendly approach with the combination of photocatalysis and electrocatalysis in less acidic pH, aiming to achieve faster mineralization of a pharmaceutical micropollutant without adding any external oxidants. TiO2/GO/loaded Ag non-active electrodes are synthesized for the degradation of bupropion hydrochloride (antidepressant drug). The present work also seeks the parametric modeling and optimization of hPEF process parameters by using R programming. Nonlinear kinetic modeling was performed for the determination of kinetic parameters. The role of selected process parameters on the mineralization of bupropion was also explained in detail. The OH• and O2•− showed their active participation in the degradation process, while Ag and UV-C played an active role in the disinfection of treated wastewater.

Efficacy of nicotine-replacement therapy, bupropion, and a combination of both for treating nicotine addiction

Background Most of the studies about the efficacy of smoking-cessation medication and its side effects were conducted in developed countries on participants who differ from Arab population in sociocultural and genetic factors. Patients and methods A randomized controlled trial was conducted on a convenient sample of 100 smokers at the smoking-cessation clinic. The participants were allocated into four groups: nicotine-replacement therapy (NRT), bupropion (BPP), combination of NRT+BPP, and placebo. Counseling was offered to all participants. Outcomes: self-reported smoking status with biochemical verification (success to stop smoking, lapse, relapse, or failure to stop smoking) at 3 and 6 months from starting treatment. Results The total success rate in four studied groups was 14% at 3 months and 8% at 6 months. There was no evidence of any statistically significant difference between any of the interventional groups (NRT, BPP, or their combination) and placebo group at 3 and 6 months as regards success rate (8, 12, 8, and 28%, respectively, at 3 months and 8, 12, 0, and 12%, respectively, at 6 months). There were no serious adverse events in the studied groups. Headache was more significantly reported by placebo group compared with all other groups (P=0.01), and urgency was more significantly reported by placebo group compared with NRT group (P=0.001). Conclusion The study found no evidence of the superior effect of NRT, BPP, or their combination over placebo in helping smokers quit smoking at 3 and 6 months. However, more withdrawal symptoms were reported by the placebo group.

Determination of 12 anti-obesity drugs in human plasma by a 96-well protein precipitation plate using HPLC-MS.

An analytical method was developed and validated for the simultaneous determination of 12 anti-obesity drugs (methylephedrine (MER), amphetamine (AMP), fenfluramine (FEN), bupropion (BUP), fluoxetine (FLU), sibutramine (SIBU), bisacodyl (BISA), bumetanide (BUM), lovastatin (LOVA), simvastatin (SIM), rimonabant (RIMO), and fenofibrate (FENO)) in human plasma by a 96-well protein precipitation plate combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). The 96-well protein precipitation plate was chosen for simultaneous pretreatment of large sample volumes, making the whole process more efficient and faster. Drugs were separated on an Agilent Poroshell 120 EC-C18 column, and detected by MS/MS under multiple reaction monitoring (MRM) mode. The developed method was validated in terms of linearity, matrix effect, accuracy and precision. A good linearity was obtained in the range of 0.1–20.0 ng mL−1 for fenfluramine, bupropion, fluoxetine, sibutramine, bisacodyl, and rimonabant; and 0.5–20.0 ng mL−1 for methylephedrine, amphetamine, bumetanide, lovastatin, simvastatin, and fenofibrate with a correlation coefficient above 0.995. The method was fully validated with an acceptable accuracy of 75.63–108.21%, matrix effect of 80.41–117.71% except for fenofibrate (76.07% at low concentration levels), and precision of 0.32–13.12%. Owing to the advantages of simple operation, high accuracy and sensitivity, this method is suitable for the rapid and simultaneous detection of 12 anti-obesity drugs in human plasma, providing support for clinically monitoring the development of adverse reactions and guiding the rational and appropriate use of weight-loss drugs for obese people.

Automated Solid Phase Extraction and Polarity-Switching Tandem Mass Spectrometry Technique for High Throughput Analysis of Urine Biomarkers for 14 Tobacco-related Compounds.

Tobacco use is the leading preventable cause of premature disease and death in the United States. Approximately, 34 million U.S. adults currently smoke cigarettes. We developed a method for automated sample preparation and liquid chromatography-tandem mass spectrometry quantitation of 14 tobacco-related analytes: nicotine (NICF), cotinine (COTF), trans-3′-hydroxycotinine (HCTF), menthol glucuronide (MEG), anabasine (ANBF), anatabine (ANTF), isonicoteine (ISNT), myosmine (MYOS), beta-nicotyrine (BNTR), bupropion (BUPR), cytisine (CYTI), varenicline (VARE), arecaidine (ARD), and arecoline (ARL). The method includes automated solid-phase extraction using customized positive-pressure functions. The preparation scheme has the capacity to process a batch of 96 samples within 4 h with greater than 88% recovery for all analytes. The 14 analytes, separated within 4.15 min using reversed-phase liquid chromatography, were determined using a triple-quadrupole mass spectrometer with atmospheric-pressure chemical ionization and multiple reaction monitoring in negative and positive ionization modes. Wide quantitation ranges, within 1.2–72,000 ng/mL, were established especially for COTF, HCTF, MEG, and NICF to quantify the broad range of biomarker concentrations found in the U.S. population. The method accuracy is above 90% while the overall imprecision is below 7%. Finally, we tested urine samples from 90 smokers and observed detection rates of over 98% for six analytes with urinary HCTF and MEG concentrations ranging from 200–14,100 and 60–57,100 ng/mL, respectively. This high throughput analytical process can prepare and analyze a sample in 9 min and along with the 14-compound analyte panel can be useful for tobacco-exposure studies, in smoking-cessation programs, and for detecting changes in exposure related to tobacco products and their use.

Ameliorative effects of alkaloid extract from Mitragyna speciosa (Korth.) Havil. Leaves on methamphetamine conditioned place preference in mice

Ethnopharmacological relevanceMitragyna speciosa (Korth.) Havil., popularly known as Kratom (KT), is a medicinal plant used for pain suppression in Southeast Asia. It has been claimed to assist drug users withdraw from methamphetamine (METH) dependence. However, its use was controversial and not approved yet. Aim of the studyThis study was conducted to characterize local field potential (LFP) patterns in the nucleus accumbens (NAc) and the hippocampus (HP) in mice with METH conditioned place preference (CPP) that were treated with KT alkaloid extract. Materials and methodsMale Swiss albino ICR mice were implanted with intracraneal electrodes into the NAc and HP. To induce METH CPP, animals were injected intraperitoneally once a day with METH (1 mg/kg) and saline (0.9% w/v) alternately and put into METH/saline compartments to experience the associations between drug/saline injection and the unique environmental contexts for 10 sessions. Control group received saline injection paired with both saline/saline compartments. On post-conditioning day, effects of 40 (KT40), 80 (KT80) mg/kg KT alkaloid extract and 20 mg/kg bupropion (BP) on CPP scores and LFP powers and NAc-HP coherence were tested. ResultsTwo-way ANOVA revealed significant induction of CPP by METH sessions (P < 0.01). Multiple comparisons indicated that METH CPP was completely abolished by KT80 (P < 0.001). NAc gamma I (30.0–44.9 Hz) and HP delta (1.0–3.9 Hz) powers were significantly increased in mice with METH CPP (P < 0.01). The elevated NAc gamma I was significantly suppressed by KT80 (P < 0.05) and the increased HP delta was significantly reversed by KT40 (P < 0.01) and KT80 (P < 0.001). In addition, NAc-HP coherence was also significantly increased in gamma I (30.0–44.9 Hz) frequency range (P < 0.05) but it was reversed by KT80 (P < 0.05). Treatment with BP did not produce significant effect on these parameters. ConclusionsThese findings demonstrated that KT alkaloid extract significantly reversed CPP scores and LFP patterns induced by METH administration. The ameliorative effects of the extract might be beneficial for treatment of METH craving and addiction.

A Bayesian population physiologically based pharmacokinetic absorption modeling approach to support generic drug development: application to bupropion hydrochloride oral dosage forms

We propose a Bayesian population modeling and virtual bioequivalence assessment approach to establishing dissolution specifications for oral dosage forms. A generalizable semi-physiologically based pharmacokinetic absorption model with six gut segments and liver, connected to a two-compartment model of systemic disposition for bupropion hydrochloride oral dosage forms was developed. Prior information on model parameters for gut physiology, bupropion physicochemical properties, and drug product properties were obtained from the literature. The release of bupropion hydrochloride from immediate-, sustained- and extended-release oral dosage forms was described by a Weibull function. In vitro dissolution data were used to assign priors to the in vivo release properties of the three bupropion formulations. We applied global sensitivity analysis to identify the influential parameters for plasma bupropion concentrations and calibrated them. To quantify inter- and intra-individual variability, plasma concentration profiles in healthy volunteers that received the three dosage forms, each at two doses, were used. The calibrated model was in good agreement with both in vitro dissolution and in vivo exposure data. Markov Chain Monte Carlo samples from the joint posterior parameter distribution were used to simulate virtual crossover clinical trials for each formulation with distinct drug dissolution profiles. For each trial, an allowable range of dissolution parameters ("safe space") in which bioequivalence can be anticipated was established. These findings can be used to assure consistent product performance throughout the drug product life-cycle and to support manufacturing changes. Our framework provides a comprehensive approach to support decision-making in drug product development.

Probing the Release of Bupropion and Naltrexone Hydrochloride Salts from Biopolymeric Matrices of Diverse Chemical Structures.

In the last decades, the notion of including excipients in the formulations, as inert substances aiding production processes, has changed and they are recently viewed as multifunctional discrete entities. It is now well documented that excipients serve several roles, spreading from the stabilization and modified release, to providing biocompatible properties and targeting moieties. The aim of this study was to develop matrix-based oral drug delivery systems of bupropion hydrochloride (BUP·HCl) and naltrexone hydrochloride (NTX·HCl), suitable for releasing these active substances in a modified manner, providing a stable level of drug release, which is simultaneously therapeutically effective and non-toxic, thus reducing side effects, after a single dose administration, throughout the gastrointestinal tract. The new formulations, employing hydroxypropylmethycellulose (HPMC K15M) (a cellulosic polymer, which, generally hydrates to form a gelatinous layer that is critical to prevent wetting and rapid drug release from the matrices), poly(methacylic acid-co-ethyl acrylate) 1:1 (Eudragit® L100-55: effective for site specific drug delivery in intestine), poly(ethylene oxide) (PEO) (7 × 106: a high molecular weight polymer, water-soluble, in micro-granular powder form), as the rate controlling polymers, were chosen to lead to a “soothing out” release pattern of these drugs, at 0 ≤ t ≤ 120 min. Moreover, the release of the two drugs from the ulvan-based tablets, was found to follow the desired profile, throughout the entire course of the dissolution experiments.

Medsafe provides bupropion update after monitoring completion

Medsafe provides bupropion update after monitoring completion

Pregnancy Has No Clinically Significant Effect on the Pharmacokinetics of Bupropion or Its Metabolites.

Bupropion (BUP) is a chiral antidepressant and smoking cessation aide with benefits and side effects correlated with parent and active metabolite concentrations. BUP is metabolized by CYP2B6, CYP2C19, and CYP3A4 to hydroxy-BUP (OH-BUP) as well as by 11β-hydroxysteroid dehydrogenase-1 and aldo-keto reductases to threohydrobupropion (Threo) and erythrohydrobupropion (Erythro), respectively. As pregnancy alters the activity of drug-metabolizing enzymes, the authors hypothesized that BUP metabolism and BUP metabolite concentrations would be altered during pregnancy, potentially affecting the efficacy and safety of BUP in pregnant women. Pregnant women (n = 8) taking BUP chronically were enrolled, and steady-state plasma samples and dosing interval urine samples were collected during pregnancy and postpartum. Maternal and umbilical cord venous blood samples were collected at delivery from 3 subjects, and cord blood/maternal plasma concentration ratios were calculated. The concentrations of BUP stereoisomers and their metabolites were measured. Paired t tests were used to compare pharmacokinetic parameters during pregnancy and postpartum. No significant changes were observed in the steady-state plasma concentrations, metabolite to parent ratios, formation clearances, or renal clearance of any of the compounds during pregnancy when compared with postpartum. The umbilical cord venous plasma concentrations of BUP and its metabolites were 30%-60% lower than maternal plasma concentrations. This study showed that there are no clinically meaningful differences in the stereoselective disposition of BUP or its metabolites during pregnancy, indicating that dose adjustment during pregnancy may not be necessary. The results also showed that the placenta provides a partial barrier for bupropion and its metabolite distribution to the fetus, with possible placental efflux transport of bupropion and its metabolites.

Electrochemical detection of bupropion drug using nanocomposite of molecularly imprinted polyaniline/Au nanoparticles/graphene oxide

Here, we developed an impedimetric nanosensor by modifying the screen-printed carbon electrode using a nanocomposite of molecularly imprinted polyaniline/gold nanoparticles/graphene oxide to facilitate the charge transfer process and increase the specific surface area of the sensor. The electropolymerization and MIP fabrication process, as well as the optimization of the electrode modification were optimized using a set of experiments. The surface morphology of the modified electrode was characterized by field emission scanning electron microscopy, energy dispersive spectroscopy and electrochemical impedance spectroscopy. The analytical assessments of the bupropion hydrochloride (BUP) electrochemical nanosensor showed a linear range from 2.0 to 990.0 nM with the limit of detection of 0.5 nM. The results of selectivity tests of the nanosensor showed a high specificity towards BUP compared to other similar molecules. Furthermore, the developed sensor was successfully applied to detect BUP in tablets and urine samples with a good recovery percentage.

Type 2 Diabetes Risk in Youth Using SSRIs Appears Lower Than Previously Reported

Type 2 Diabetes Risk in Youth Using SSRIs Appears Lower Than Previously Reported