A novel ultrasensitive derivatization-free synchronous fluorescence approach for the simultaneous analysis of propofol and nalbuphine in human plasma and dosage forms: Compliance with greenness and blueness metrics.

Development of inhalable spray dried nalbuphine hydrochloride powders.

Background: Shivering following spinal anaesthesia is a common postoperative complication that can lead to patient discomfort, increased metabolic demand, and delayed recovery. Effective management of post-spinal shivering is essential for optimizing patient outcomes and enhancing perioperative care. Among pharmacologic agents used to control shivering, tramadol and nalbuphine are widely employed due to their central mechanisms of action. However, limited data exists comparing their efficacy, particularly within the local clinical setting. Objective: To compare the efficacy of intravenous nalbuphine and tramadol in controlling shivering following spinal anaesthesia. Methods: This randomized controlled trial was conducted in the Anesthesiology Department of Khyber Teaching Hospital, Peshawar, from 05-February to 05-August 2024. A total of 74 patients aged 18–75 years who developed shivering after spinal anaesthesia were enrolled and randomized into two equal groups. Group A (n = 37) received intravenous nalbuphine hydrochloride (0.06 mg/kg) and Group B (n = 37) received intravenous tramadol hydrochloride (1 mg/kg), both diluted in normal saline and administered over five minutes. The primary outcome was the time to control shivering, assessed by an experienced anesthesiologist. Data were analyzed using SPSS version 23, with a p-value ≤ 0.05 considered statistically significant. Results: The mean age was 53.30 ± 14.55 years in Group A and 51.65 ± 14.70 years in Group B. Mean time to control shivering was 4.92 ± 1.01 minutes in the nalbuphine group and 4.11 ± 0.97 minutes in the tramadol group, showing a statistically significant difference (p = 0.001). Conclusion: Tramadol was more effective than nalbuphine in rapidly controlling shivering following spinal anaesthesia, making it a preferable option for prompt perioperative thermoregulation.

Background: Effective postoperative analgesia is crucial for early mobilization and recovery in orthopaedic surgeries. This study compares the efficacy and safety of Nalbuphine Hydrochloride and Tramadol Hydrochloride for postoperative pain management in patients undergoing orthopaedic procedures. Methods: A double-blind, randomized controlled trial was conducted involving 100 patients who underwent various orthopaedic surgeries. Patients were randomly assigned to receive either Nalbuphine Hydrochloride or Tramadol Hydrochloride postoperatively. The primary outcomes measured were pain intensity using the Visual Analogue Scale (VAS) at specific time intervals and adverse effects. Secondary outcomes included hemodynamic stability and the need for additional analgesic doses. Results: Patients receiving Nalbuphine reported significantly lower VAS scores at 30 minutes (1.80 ± 0.50) and 540 minutes (2.00 ± 0.29) post-operation compared to those receiving Tramadol (2.21 ± 0.41 and 2.38 ± 0.58, respectively; p<0.01). Nalbuphine also demonstrated fewer adverse effects such as nausea and vomiting. Hemodynamic parameters were stable and comparable between the two groups. Conclusion: Nalbuphine Hydrochloride provides superior analgesia with fewer adverse effects compared to Tramadol Hydrochloride in the postoperative management of orthopaedic patients, making it a potentially preferable option for pain control in this population.

A validated stability-indicating HPTLC densitometric method for the estimation of Nalbuphine hydrochloride in bulk and pharmaceutical formulation

In pediatric practice, nalbuphine hydrochloride can be administered by continuous infusion through a multiport manifold or Y-site connection over 24 h in a 60 mL polypropylene syringe unprotected from light at concentrations ranging from 52.1 µg.mL-1 to 333.3 µg.mL-1 in normal saline (NS). To limit the need for multiple injections, nalbuphine hydrochloride may be co-administered with other drugs. Its stability and compatibility were already studied at concentration ranges equal or higher than 1.0 mg.mL-1. However, when nalbuphine hydrochloride needs to be diluted for a pediatric administration its stability in NS over 24 h of light exposure at ambient temperature and its compatibility with other drugs have never been studied before. A novel chromatographic method using high-performance liquid chromatography (HPLC) was validated by the International Council for Harmonisation (ICH) Q2 (R1) guidelines. The stability of nalbuphine hydrochloride and the appearance of degradation products under five experimental conditions (light, heat, oxidation, basicity, and acidity) were monitored by HPLC-UV for 24 h at ambient temperature at three concentrations administered in pediatric departments (52.1 µg.mL-1, 166.7 µg.mL-1 and 333.3 µg.mL-1). The physical compatibility of nalbuphine hydrochloride with 1:1 (v/v) mixtures of selected drugs used in pediatrics was evaluated by visual inspection and with a 10 µm and 25 µm sub-visible particle counter. Our nalbuphine hydrochloride quantification method has been validated and was stability-indicating. The stability of nalbuphine hydrochloride and the forced degradation assay (light, heat, oxidation, basicity, and acidity) studied for the three concentrations of nalbuphine hydrochloride diluted in 48 mL of NS and stored in a 60 mL polypropylene syringe unprotected from light were compliant for at least 24 h at ambient temperature. Nalbuphine hydrochloride in NS was found to be compatible with several drugs, but was incompatible with furosemide and amphotericin B. Nalbuphine hydrochloride can be administered in pediatric practice using a syringe pump for 24 h. However, drug-drug incompatibilities need to be considered when it is administered through a multiport manifold or Y-site connection.

Remimazolam is a new type of ultra-short-effect intravenous anesthetic, that may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. The aim of this clinical study was to compare the efficacy and safety of two different doses of remimazolam with propofol for sedation during colonoscopy. 225 subjects, aged 18 to 80 years, with American Society of Anesthesiology physical status I-III, were scheduled to undergo colonoscopy. All the subjects were randomly assigned to three groups, Low-Rem group (low dose remimazolam, 0.15 mg/kg, iv, n = 75), High-Rem group (high dose remimazolam, 0.2 mg/kg, iv, n = 75), and Propofol group (propofol 2 mg/kg, iv, n = 75). Every individual in this trial was given nalbuphine hydrochloride (0.2 mg/kg, iv) before administration of remimazolam or propofol. The primary outcome was the success rate of sedation. Haemodynamic parameters and adverse events were recorded to evaluate safety. Satisfaction of sedation from patients, anesthesiologists and gastroenterologists were also recorded. The success rate of colonoscopy procedure was 100% in both High-Rem and Propofol groups, but it was 89% in Low-Rem group (p < 0.05). Furthermore, the induction time of anesthesia was shorter in Propofol group, when compared to the Low-Rem group and the High-Rem group (p < 0.05). The recovery time in Low-Rem group, High-Rem group, and Propofol group was 2.33, 2.43, and 3.21 min (p < 0.05) respectively, and the time of discharge was 25.00, 25.01, and 27.56 min (p < 0.05) respectively. Simultaneously, the incidence of adverse events such as hypotension, bradycardia, and respiratory depression in the remimazolam groups were significantly lower than that in the propofol group. No significant differences were observed among the three groups in Ramsay scale, BPS-NI scale, and Limb movement classification. Moreover, patients, anesthesiologists, and gastroenterologists were all satisfied with the sedation process. Remimazolam can be used safely and effectively for colonoscopy. 0.2 mg/kg remimazolam and propofol have the same sedation success rate and more stable hemodynamics and fewer side effects than propofol. ChiCTR2100054053.

Chickens (Gallus gallus domesticus) are commonly used for research, food production, show, and companionship. Sedation is often necessary for sample collection, imaging, or treatment. Dexmedetomidine has been previously used to sedate birds, often with other sedatives. Butorphanol tartrate, a Schedule IV controlled substance, is commonly used but presents regulatory challenges. Nalbuphine hydrochloride, an opioid with similar receptor affinity to butorphanol, has potential as a noncontrolled alternative. Although information regarding nalbuphine use in birds is limited, its noncontrolled status makes it more accessible. The purpose of this study was to determine the effective dose to produce sedation in 50% (ED50) of patients and to estimate the calculated effective dose of dexmedetomidine in combination with either butorphanol (DexBut) or nalbuphine (DexNal) in domestic hens to sedate 99% of patients (ED99). Eighteen 33-week-old laying Buff Orpington hens were divided into 2 groups: one receiving DexBut (n = 9) and the second receiving DexNal (n = 9). Each hen was sedated with varying doses of intramuscular dexmedetomidine with a constant dose of either 2 mg/kg IM butorphanol or 12.5 mg/kg IM nalbuphine by an up-and-down design. Sedation was determined using a clinically applicable scoring system. The ED50 values of dexmedetomidine with 2 mg/kg IM of butorphanol, calculated by both the up-and-down method and logistic regression, were 38 and 49 µg/kg, respectively, while the ED50 values of dexmedetomidine in combination with 12.5 mg/kg IM of nalbuphine were 19 and 18 µg/kg, respectively. The estimated dexmedetomidine ED99 values with butorphanol or nalbuphine were 51 and 19 µg/kg, respectively. Multiple chickens in both groups exhibited open-mouth breathing and comb pallor but no lasting morbidity or mortality occurred. Combinations of DexBut or DexNal should be considered for sedation of domestic chickens.

Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe hepatic impairment (Child–Pugh A, B, and C, respectively) compared to healthy matched subjects. NAL exposures were similar for subjects with mild hepatic impairment as compared to healthy subjects and nearly three-fold and eight-fold higher in subjects with moderate and severe hepatic impairment, respectively. Datasets obtained for healthy, moderate, and severe hepatic impaired groups were modeled with a mechanistic model that incorporated NAL hepatic metabolism and enterohepatic recycling of NAL and its glucuronidated metabolites. The mechanistic model includes a continuous intestinal absorption model linked to semi-physiological liver–gallbladder–compartmental PK models based on partial differential equations (termed the PDE-EHR model). In vitro studies indicated that cytochromes P450 CYP2C9 and CYP2C19 are the major CYPs involved in NAL oxidation, with glucuronidation mainly catalyzed by UGT1A8 and UGT2B7 isozymes. Complex formation and elimination kinetics of NAL and four main metabolites was well predicted by PDE-EHR. The model is expected to improve predictions of drug interactions and complex drug disposition.

Background In anaesthesiology, intrathecal drugs play pivotal roles in spinal anaesthesia. Despite their ability to induce a high sensory block, bupivacaine alone may not be adequate for postoperative analgesia. It often requires a substantial dose of postoperative rescue analgesia to manage pain effectively. Thus, we studied the efficacy of nalbuphine 1.5 mg injected intrathecally as an adjuvant in endoscopic urological surgery. Materials and methods Sixty patients undergoing endoscopic urological surgery were equally divided into two study groups: group B (injection 0.5% hyperbaric bupivacaine 15 mg (3 ml) plus sterile NS 0.15 ml) and group N (injection 0.5% hyperbaric bupivacaine 15 mg (3 ml)+nalbuphine 1.5 mg (0.15 ml)). The first appearance of the sensory and motor blockages and duration required to attain complete sensory and motor threshold was noted. All vitals were recorded. After surgery, it was recorded when the patient first needed rescue analgesia (injection paracetamol 1 gm IV). Any adverse effects were recorded and addressed. The statistical analysis was conducted using IBM SPSS Statistics for Windows, V. 22.0 (IBM Corp., Armonk, NY), with p<0.05 indicating significance in both groups' operations. Results Intrathecal nalbuphine as an adjuvant caused an earlier onset of sensory and motor inhibition, delayed two-segment regression, and prolonged postoperative anaesthesia. The control group experienced sensory block at 3.33±0.61 minutes, while the nalbuphine group had a mean onset of 2.66±0.92 minutes (p=0.001). The patient who received nalbuphine had a mean regression time of 119.60±14.549 minutes, whereas the bupivacaine group had a mean regression time of 88.43±17.196 minutes. Group N had a considerably longer duration of postoperative analgesia, lasting 264.97 minutes, compared to group B's 198.50 minutes (p<0.001). Intrathecal nalbuphine did not influence vital indicators such as heart rate, respiration rate, and oxygen saturation. Conclusion To conclude, endoscopic urological surgery patients who received a subarachnoid block with 1.5 mg (0.15 ml) of nalbuphine hydrochloride with 0.5% hyperbaric bupivacaine 15 mg (3 ml) had longer postoperative pain relief than those who received 3 ml of intrathecal bupivacaine (15 mg). Urinary retention and pruritus were absent. Intrathecal nalbuphine with hyperbaric 0.5% bupivacaine is deemed safe with minimal side effects in endoscopic urology surgery.

Nalbuphine (NAL) is a κ-agonist/μ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR). Clinical pharmacokinetic (PK) data sets in healthy subjects from three trials that included IV, oral solution, and ER tablets in fed and fasted state and two published trials were used to parametrize a novel partial differential equation (PDE)-based model, termed "PDE-EHR" model. Experimental inputs included in vitro dissolution and permeability data. The model incorporates a continuous intestinal absorption framework, explicit liver and gall bladder compartments, and compartments for systemic drug disposition. The model was fully PDE-based with well-stirred compartments achieved by rapid diffusion. The PDE-EHR model accurately reproduces NAL concentration-time profiles for all clinical data sets. NAL disposition simulations required inclusion of both parent and glucuronide recirculation. Inclusion of intestinal P-glycoprotein efflux in the simulations suggests that NAL is not expected to be a victim or perpetrator of P-glycoprotein-mediated drug interactions. The PDE-EHR model is a novel tool to predict EHR and food/formulation effects on drug PK. The results strongly suggest that even intravenous dosing studies be conducted in fasted subjects when EHR is suspected. The modeling effort is expected to aid in improved prediction of dosing regimens and drug disposition in patient populations.

Developing an effective antidote for fentanyl-induced overdose to achieve timely reversal is an unmet public health need. Previously, we found that naloxone derivative NX90 with mild κ-opioid agonistic properties was three-fold more effective than the parent naloxone in reversing a fentanyl overdose in rats. To investigate whether κ-agonistic properties could indeed augment the robustness of overdose reversal, we evaluated a κ-agonist/µ-antagonist nalbuphine (NB) as well as its combinations with naloxone (NX) in a fentanyl overdose model in rodents. An administration of either NB or NX as single agents at 0.1 mg/kg doses produced a full recovery in 90 ± 9.9 min and 11.4 ± 2.7 min, respectively. A higher dose of NX at 0.2 mg/kg reversed an overdose within 4.8 ± 1.0 min. In contrast to that, the coadministration of NB and NX at 0.1 mg/kg each produced a synergistic effect, with overdose reversal in 3.4 ± 0.2 min. The coadministration of NX and NB at sub-therapeutic doses of 0.05 mg/kg each was also 1.2-fold more effective than NX at 0.2 mg/kg. We further found that co-administration of NB at different doses (0.025, 0.05, 0.1 mg/kg) and ratios (1:4 and 1:1) with NX had differential effects on overdose reversal, cardiorespiratory liabilities, and analgesia.

The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min-1 ± SD), 17311.01 ± 7227.32 (min·ng·mL-1 ± SD), 675.6 ± 337.13 (ng·mL-1 ± SD), and 44.5 ± 13.8 (mL·min-1·kg-1 ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 - ∞), and maximum plasma drug concentration were 129 ± 52.9 (min-1 ± SD), 20826.5 ± 14376.2 (min·ng·mL-1), and 368.03 ± 503.78 (ng·mL-1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.

Objectives: To compare the eff ectiveness of pain control between Alvogyl and Zinc Oxide in individuals experiencing dry socket.Materials and Methods: This randomized controlled trial was conducted at Bacha Khan College of Dentistry, Mardan with the inclusion of 60 participants (30 in each group). Inclusion criteria comprised patients with dry socket occurring two or three days after extraction, aged between 12 and 60 years, of both genders, and Pakistani nationals. Exclusion criteria included medically compromised patients, pregnant females, individuals with a history of radiotherapy, and those with any known allergy to eugenol. One group was treated with Alvogyl, while the other received Zinc oxide eugenol packing. The time to initial pain relief (in minutes) and complete cessation of pain (in days) were recorded through phone calls. The Student t-test was employed to compare the outcome variable between the two groups.Results: The mean age was 29.27 ± 6.60 years, with 30 females (50%) and 30 males (50%). The time for initial pain relief was signifi cantly longer for ZnO Eugenol (26.04 ± 3.82 minutes) compared to Alvogyl (6.81 ± 2.25 minutes), with a statistical signifi cance of p &lt; 0.001. Similarly, the time for fi nal pain relief was also significantly longer for ZnO Eugenol (8.78 ± 0.24 days) compared to Alvogyl (6.88 ± 0.64 days), with a p-value of less than 0.001.Conclusion: Based on our results, it can be concluded that Alvogyl is superior to Zinc oxide eugenol in the management of dry socket, particularly in terms of pain relief.

Amphiphilic NLC-Gel formulation loaded with Sebacoyl dinalbuphine ester and Nalbuphine for localized postoperative pain management

Ultrasound-guided pericapsular nerve block compared with IV opioids in hip injuries: A randomised controlled trial

The article discusses the peculiarities of forensic examination of nalbuphine hydrochloride, a prescription medicine that can be purchased without a prescription in many pharmacies. At present, in Ukraine, nalbuphine is not subject to subject-quantitative accounting in healthcare facilities and by pharmaceutical manufacturers, but in some countries it is included in the list of narcotic drugs. It is emphasised that nalbuphine hydrochloride is a synthetic opioid analgesic, which is chemically similar to morphine and phenanthrene. In terms of pharmacological action, it belongs to the group of opioid receptor agonists-antagonists (pentazocine, buprenorphine, butorphanol). The article provides a brief overview of the effectiveness of nalbuphine for pain relief in various cases, as well as examples of abuse of opioids in combination preparations and facts of non-medical use of nalbuphine. The effectiveness of opioids as painkillers is undeniable, but today, given the risk/benefit ratio, the expediency of their long-term use is questionable. There are more and more recommendations to avoid the use of opioids. Nalbuphine in combination with other psychotropic substances, medicines and in large doses is life-threatening, so it is proposed to further study and control it more deeply at the state level by amending the Resolution of the Cabinet of Ministers of Ukraine “On Approval of the List of Narcotic Drugs, Psychotropic Substances and Precursors” of 6 May 2000 No. 770, in particular, to classify nalbuphine as a narcotic drug. The article analyses the peculiarities of sampling and sample preparation, the main stages of chemical research of this potentially dangerous opioid using thin-layer chromatography, infrared spectroscopy, gas chromatography with a mass-selective detector. It is emphasised that the experimental data presented in the article will help in choosing the most appropriate methods and conditions for the study of nalbuphine, and will allow an objective assessment of the results of expert research.

Synthesis and characterization of N-MPG/CuS flower-like/MXene to modify a screen-printed carbon electrode for electrochemical determination of nalbuphine

We report a highly uniform nanocomposite of polyglutamic acid (PGA) and gold nanoparticles (AuNPs) electrodeposited on a recycled battery graphite electrode (BGE) for the detection of Nalbuphine (NB), a semi-synthetic opioid. The sensor was optimized and characterized morphologically (via scanning electron microscopy, atomic force microscopy, and energy dispersive X-ray analysis) and electrochemically (via cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy). Under optimized conditions, the PGA/AuNPs/BGE revealed two linear ranges, 2.5 × 10−8 to1.0 × 10−6 M, and 2.0 × 10−6 to 1.0 × 10−4 M for Nalbuphine (NB), that is equivalent to 9.825 × 10−3 to 0.393 μg ml−1 and 0.786 to 39.30 μg ml−1, with R2 = 0.995 and 0.994, respectively, and showed good catalytic activity for the determination of nalbuphine in the presence of tramadol and the oxidation potential of these opioid analgesic drugs were separated. The sensor was successfully applied for the detection of NB in its pharmaceutical formulations, spiked urine, and human plasma samples, without applying any sample pretreatment, at a recovery range of 99 ± 0.03 to102 ± 0.02% and thus, the developed can be considered as a promising approach for NB abuse testing in clinical and forensic agencies.

Purpose: To determine the features of the untrastructural reorganization in the rat retina by the end of week 4 and week 6 of experimental opioid exposure. Material and Methods: Forty-eight adult male albino rats (weight, 200-250 g; age, 4.5 months) were used in this study. They received nalbuphine hydrochloride intramuscularly daily for 42 days. Particularly, the drug was administered daily at a dose of 0.212 mg/kg for weeks 1 and 2, 0.225 mg/kg for weeks 3 and 4, and 0.252 mg/kg for weeks 5 and 6. In this way, we experimentally created the conditions of chronic opioid exposure. Animals were divided into three groups. Group 1 (19 animals) received nalbuphine for 28 days, and group 2 (19 animals), for 42 days. Group 3 (control group) comprised 10 animals. Of these, 5 animals were treated with normal saline at a dose of 0.22 mg/kg intramuscularly daily for 28 days, and the rest were treated in a similar manner for 42 days. Transmission electron microscopy studies of the rat retina were conducted in a routine manner. Results: By the end of week 4 of experimental opioid exposure, there was an increase in the number of retinal microvessels with signs of hyperemia and degenerative changes in retinal pigment epithelium (RPE) cells, increase in the destruction of membranous discs of photoreceptor outer segments, necrobiotic changes in the nuclei of individual photoreceptors, axonal degeneration in the outer and inner plexiform layers, degenerative changes in retinal horizontal neurons, and the appearance of necrotic structural changes in the cytoplasm of bipolar and amacrine cells. By the end of week 6, there was a further increase in hyperemia of retinal vessels and degenerative and necrotic changes in individual RPE cells and photoreceptor outer segments. In addition, we observed destruction and shortening of mitochondrial cristae of photoreceptor inner segments, necrotic nuclear changes in individual photoreceptors, degeneration of axons of the outer and inner plexiform layers, degenerative and necrotic changes in bipolar and amacrine cells, hypertrophic Müller cell processes, degeneration of ganglion cells, and vascular hyperemia and moderate perivascular edema in the outer and inner plexiform layers. Conclusion: Therefore, in the current rat study, after a 4-week exposure to daily nalbuphine injections at a dose ranging 0.212 to 0.253 mg/kg, there was ultrastuctural evidence of destructive processes in the RPE and photoreceptor outer segments, axonal degeneration in the outer and inner plexiform layers, degenerative and necrotic changes in bipolar and amacrine cells, hypertrophic Müller cell processes, ganglion cell degeneration and hyperemia due to an impaired retinal microcirculatory ultrastructure. At week 6 of the experiment, there was evidence of increased destructive and degenerative processes in structural components of the retina.