暂无摘要。

BACKGROUND: A Non-Ergot Dopamine Agonist (NEDA) rotigotine has been designed as a new transdermal drug delivery system.
OBJECTIVE: To maintain optimum homogeneity in drug content, the rotigotine transdermal patch was developed utilizing a solvent casting technique.
METHODS: The characteristics of a transdermal patch, including patch weight, folding endurance, patch thickness, surface morphology, tensile strength, swelling rate, surface pH, in vitro release studies, water retention rate, uniformity of drug content, and ex-vivo permeation studies, were determined.
RESULTS: In vitro drug release studies unequivocally demonstrated that drug release controlled polymer interactions. There was no apparent lag period before the drug release rate started to decline. The developed patch showed 70 ± 1.18 % of prolongation of drug release within 24 hours. The result of the penetration studies demonstrated that 61 ± 2.52% of rotigotine permeated through the epidermal barrier within 24 h.
CONCLUSIONS: The developed transdermal patch comprising rotigotine was evidently placed on the dermis layer, and an appropriate dose was delivered into circulation for a longer time based on the aforementioned factors. The findings of this study illustrate the effective approach of transdermal patches to treat Parkinson\'s disease.

Parkinson\'s disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of -15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a \'drug-free\' supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment.

This study aimed to enhance the stability of the Rotigotine (ROT) patch using polymers as crystal inhibitors. Three polymers (Poloxamer 188, Soluplus, TPGS) were selected as crystal inhibitors to formulate ROT patches with varying drug loadings (20%, 40%, 60%, and 80%, w/w). SEM and XRD analysis revealed that the Soluplus and Soluplus-TPGS groups with a high concentration (80%, w/w) of ROT could be stored at room temperature for at least 90 days without crystallization. Moreover, the crystallization nucleation time and growth rate were utilized to assess the ability of Poloxamer 188, Soluplus, and TPGS to hinder the formation of ROT crystals and slow down its crystallization rate. Molecular docking results elucidated the intermolecular forces between ROT and different polymers, revealing their mechanisms for crystal inhibition. The ROT-Soluplus-TPGS combination exhibited the lowest binding free energy (-5.3 kcal/mol), indicating the highest binding stability, thereby effectively reducing crystal precipitation. In vitro skin permeation studies demonstrated that ROT patches containing crystal inhibitors exhibited promising transdermal effects. With increasing ROT concentration, the cumulative drug permeation substantially increased, while the lag time was notably reduced. This study offers novel insights for the development of ROT patches.

Transdermal rotigotine (RTG) therapy is prescribed to manage Parkinson\'s disease (Neupro® patch). However, its use is suffered from application site reactions. Herein, drug nanocrystalline suspension (NS)-loaded hydrogel (NS-HG) employing polysaccharides simultaneously as suspending agent and hydrogel matrix was constructed for transdermal delivery, with alleviated skin irritation. RTG-loaded NS-HG was prepared using a bead-milling technique, employing sodium carboxylmethyl cellulose (Na.CMC) as nano-suspending agent (molecular weight 90,000 g/mol) and hydrogel matrix (700,000 g/mol), respectively. NS-HG was embodied as follows: drug loading: ≤100 mg/mL; shape: rectangular crystalline; crystal size: <286.7 nm; zeta potential: -61 mV; viscosity: <2.16 Pa·s; and dissolution rate: >90 % within 15 min. Nuclear magnetic resonance analysis revealed that the anionic polymers bind to RTG nanocrystals via charge interaction, affording uniform dispersion in the matrix. Rodent transdermal absorption of RTG from NS-HG was comparable to that from microemulsions, and proportional to drug loading. Moreover, NS-HG was skin-friendly; erythema and epidermal swelling were absent after repeated application. Further, NS-HG was chemically stable; >95 % of the drug was preserved up to 4 weeks under long term (25 °C/RH60%), accelerated (40 °C/RH75%), and stress (50 °C) storage conditions. Therefore, this novel cellulose derivative-based nanoformulation presents a promising approach for effective transdermal RTG delivery with improved tolerability.

BACKGROUND: Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture.
METHODS: PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks).
RESULTS: Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS.
CONCLUSIONS: This meta-analysis demonstrated that DAs significantly affect sleep parameters.

We report two cases who had been diagnosed with major depression, but found to have periodic limb movement disorder (PLMD) or restless legs syndrome (RLS) as major disorder. Both patients had difficulties in occupational and/or daily lives. In neither case, antidepressants were effective in symptom remission. In contrast, rotigotine transdermal patch was effective not only for core symptoms of PLMD or RLS but also for accompanying depressive symptoms. Since PLMD and RLS are associated with dopaminergic dysfunction etiologically, a dopamine receptor agonist rotigotine might be a good choice for patients with PLMD or RLS accompanying depression.

BACKGROUND: This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG).
METHODS: We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed.
RESULTS: This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP.
CONCLUSIONS: The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.

One of the most common neurodegenerative illnesses is Parkinson\'s disease (PD). Rotigotine (RTG) is a dopamine agonist that exerts anti-Parkinsonian effects through dopamine receptor agonism to improve motor symptoms and overall performance in PD patients. In this study, an in situ liquid crystal gel called rotigotine-gel (RTG-gel) was developed using soya phosphatidyl choline (SPC) and glycerol dioleate (GDO) to provide long-acting slow-release benefits of rotigotine while minimizing side effects. This study prepared the RTG-gel precursor solution using SPC, GDO, and ethanol (in the ratio of 54:36:10, w/w/w). The internal structures of the gel were confirmed by crossed-polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). The rheological properties of the RTG-gel precursor solution indicate a favorable combination of low viscosity and excellent flowability. The gel that produced during water absorption was also highly viscous and structurally stable, which helped to maintain the drug delayed release at the injection site. In vitro release assays showed that the in vitro release of RTG-gel followed Ritger-Peppas. The RTG-gel precursor solution was administered by subcutaneous injection, and the results of in vivo pharmacokinetic tests in SD rats showed that the plasma elimination half-life (t1/2) was 59.28 ± 16.08 h; the time to peak blood concentration (Tmax) was 12.00 ± 10.32 h, and the peak concentration (Cmax) was 29.9 ± 10.10 ng/mL. The blood concentration remained above 0.1 ng/mL for 20 days after administration and was still detectable after 31 days of administration, and the bioavailability of RTG can reach 72.59%. The results of in vitro solvent exchange tests showed that the RTG-gel precursor solution undergoes rapid exchange upon contact with PBS, and the diffusion of ethanol can reach 48.1% within 60 min and 80% within 8 h. The results of cytotoxicity test showed 89.27 ± 4.32% cell survival after administration of the drug using RTG-gel. The results of tissue extraction at the administration site showed that healing of the injection site without redness and hemorrhage could be observed after 14 days of injection. The results of tissue section of the administered site showed that the inflammatory cells decreased and granulation tissue appeared after 14 days of administration, and there was basically no inflammatory cell infiltration after 35 days of administration, and the inflammatory reaction was basically eliminated. It shows that RTG-gel has some irritation to the injection site, but it can be recovered by itself in the later stage, and it has good biocompatibility. In summary, RTG-gel might be a potential RTG extended-release formulation for treating PD.

End-of-life (EOL) care for Parkinson\'s disease (PD) can be challenging when oral medications are no longer tolerated.
To assess EOL prescribing for people with PD (PWP), focusing on rotigotine dosing and proxy measures of distress: benzodiazepine and opioid use.
A retrospective audit of patient records from PWP who died between January 2019 and May 2022 at the Royal Hobart Hospital (RHH), Australia, was conducted. Data was systematically collated on demographics, symptoms, levodopa equivalent daily dose (LEDD) and rotigotine, oral morphine equivalent (OME) and benzodiazepine doses in the last 72 hours of life .
Pain (72%), respiratory secretions (66%) and agitation (66%) were the most documented EOL symptoms. 83% (n = 52) of PWP were eligible for rotigotine and, of those, 13% (n = 7) received the correct dose, 38% (n = 20) a lower dose, 12% (n = 6) a higher dose and 37% (n = 19) did not receive any. Rotigotine dose was positively associated with total (P = 0.016) and PRN (P = 0.037) benzodiazepine dose. LEDD was positively associated with total benzodiazepine (P = 0.018) and total OME dose (P = 0.046). Contraindicated dopamine antagonists were prescribed for 43% of PWP and administered in 31% of those cases.
Rotigotine dose and admission LEDD were both associated with proxy measures of distress in the last 72 hours of life. This suggests cautious use of rotigotine at EOL. LEDD may help identify patients at risk of distress. Rates of inappropriate prescribing and symptom prevalence were high, indicating a need for further staff education to optimize the care of PWP.