Drug Mixtures Research Articles

Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023

Forty-eight (48) drug products (DPs) containing amorphous solid dispersions (ASDs) have been approved by the U.S. Food and Drug Administration in the 12-year period between 2012 and 2023. These DPs comprise 36 unique amorphous drugs. Ten (10) therapeutic categories are represented, with most DPs containing antiviral and antineoplastic agents. The most common ASD polymers are copovidone (49%) and hypromellose acetate succinate (30%), while spray drying (54%) and hot melt extrusion (35%) are the most utilized manufacturing processes to prepare the ASD drug product intermediate (DPI). Tablet dosage forms are the most common, with several capsule products available. Line extensions of several DPs based on flexible oral solids and powders for oral suspension have been approved which provide patient-centric dosing to pediatric and other patient populations. The trends in the use of common excipients and film coating types are discussed. Eighteen (18) DPs are fixed-dose combinations, and some contain a mixture of amorphous and crystalline drugs. The DPs have dose/unit of amorphous drug ranging from <5 mg up to 300 mg, with the majority being ≤100 mg/unit. This review details several aspects of DPI and DP formulation and manufacturing of ASDs, as well as trends related to therapeutic category, dose, and patient-centricity.

Preparation and Evaluation of Herbal Oil

Herbal formulations always have lesser or no side effects comparatively with synthetic. The aim of present study involves preparation of herbal hair oil using the herbal ingredients like., Amla, Hibiscus, Bhringraj, Jatamansi, Raw garlic, Muskmelon seeds, Moringa, Curry leaves, Guava leaves, Papaya leaves, Methi, Mimosa Pudica and Spring onion. Based on the above observations, mixture of crude drugs was prepared in the form of herbal hair oil by boiling method. We have used five formulas using different herbal drugs and all the formulation are showing anti-hairfall property with someof other beneficial activities like anti-dandruff activity, improves blood circulation to the scalp and roots, reduce hair pigmentation, anti-fungal activity, reducing the whitening of the hair. The formulate dherbal oil was evaluated by using various parameters such as Organoleptic properties, specific gravity, stability, viscosity, Acid value, pH etc. and the value obtained from it are found to be similar to that of the standard values like there is no sedimentation, no grittiness and shows satisfying organoleptic properties and the results were determined and are reported in this work. The goal of the present study is herbal have the effective formulation for the hair care or in hair treatment

Simultaneous Removal of Seven Pharmaceutical Compounds from a Water Mixture Using Modified Chitosan Adsorbent Materials

Pharmaceuticals are used to improve the lives of people across the globe. The high demand for their fabrication and use causes a very serious environmental threat since their presence is ubiquitous in aqueous matrices. For this reason, the synthesis, characterisation, and efficiency of three chitosan-based materials to eliminate pharmaceutical mixtures from aqueous solutions were examined in the present study. The target mixture comprised seven widely used drugs: carbamazepine, cyclophosphamide, adefovir, levofloxacin, metronidazole, glibenclamide, and trimethoprim. The grafting of poly(ethylene imine) and poly(acrylamide) on the chitosan structure allowed its physical characteristics to be controlled. An adsorption assessment was performed at different pH values, and it was concluded that pH = 4 was the optimum value. The adsorption kinetics revealed that the adsorption of a drug mixture involves a combination of physical and chemical adsorption. The adsorption process appeared to be finished after 1 h for all compounds of the studied mixture, with CS-AMI exhibiting the fastest kinetics. Mass adsorption experiments were also carried out to determine its effects. Overall, the grafting process significantly increased the adsorption capacity over the pristine material. Specifically, the highest capacity increase for CS-PEI was ~220% for carbamazepine, and for CS-AMI, it was 158% for trimethoprim. FT-IR, SEM, and XRD were used for the characterisation of the polymers. Based on the findings, the three materials are suggested as very effective adsorbents for the elimination of medicine residues from aqueous matrices.

Phase behaviour and thermodynamics of triton X-100 + metformin hydrochloride mixture: influences of several polyols and polymer media

The applications of surfactants and drugs in a wide variety of fields such as pharmaceuticals, food industry, textile, fabrics, etc. are increasing significantly. Herein, we investigated the clouding behavior and thermodynamics of triton X-100 (TX-100) and metformin hydrochloride (MNH) drug mixture in the effect of several polyols and polyethylene glycol (PEG) polymer. The phase separation behavior of the mixture of TX-100 + MNH has been deduced with the help of the cloud point technique. The cloud point (CP) values for the TX-100 and drug mixtures were documented in a decreased and increased manner with the augmentation of the concentration of polyol and PEG respectively. With the subsequent enhancement of polyol and PEG content, the CP values were recorded in the following order: C P H 2 O + PEG > C P H 2 O + fructose > C P H 2 O + glucose > C P H 2 O + galactose > C P H 2 O + maltose . The standard enthalpy change ( Δ H c o ) and entropy change ( Δ S c o ), of TX-100 + MNH mixture in aq. polyols solutions were documented as negative; the negative values reduce in magnitudes with the polyols contents and become positive at the highest polyol content while opposite trend was obtained in presence of PEG. The presence of electrostatic and hydrophobic interactions among TX-100/MNH/polyols/polymer has been recommended as the interaction forces.

A randomised trial comparing block characteristics of a mixture versus sequential injections of lignocaine and ropivacaine for supraclavicular brachial plexus nerve block in patients undergoing upper limb surgery.

There is no consensus on the appropriate use of mixtures of local anaesthetic drugs in various combinations for nerve blocks. We intended to compare short-acting lignocaine and long-acting ropivacaine as a mixture versus undiluted sequential injections on block characteristics of ultrasound-guided (USG) supraclavicular brachial plexus block for upper limb surgeries. A double-blinded randomised study was conducted on 64 adult patients scheduled for upper limb surgery who received 15 mL each of 2% lignocaine with adrenaline and 0.75% ropivacaine as a 1:1 mixture in the mixed group (Group M) or sequential injections in the sequential group (Group S) by using a USG technique. The primary outcome was the percentage of participants with complete four nerve sensory blocks at 10 minutes post block injection. Secondary outcomes were sensory and motor block characteristics till 30 minutes, total duration of analgesia, sensory and motor block, and complications. Demographic characteristics and time taken for the procedure were similar. The percentage of participants with a complete four-nerve sensory block at 10 minutes was higher in Group S (69%) versus Group M (41%) (P = 0.04). Complete sensory and motor block rates were similar at 30 minutes. The block procedure time, total duration of analgesia, and sensory and motor block were similar in both groups. There were no major complications. Sequential lignocaine-ropivacaine, compared to the mixed injection technique, has a higher initial rate of sensory and motor block onset with a similar total block duration.

Exploration of the effect of NaCl/urea on aggregation process of imipramine hydrochloride drug and TX-165 mixture: A surface tension and UV–visible study

In this research, mixed micellization analysis of imipramine hydrochloride (IMP), an antidepressant drug with nonionic TX-165 surfactant has been investigated entirely via tensiometry and UV–visible techniques. Influence of distinct solvents of certain concentration (aqueous/50 mmol.kg−1 NaCl/500 mmol.kg−1 urea) was also detected on mixed association behavior of IMP+TX-165 mixtures. As compared to the aqueous system, higher nonideality in IMP+TX-165 in NaCl solution was detected while in the urea system was found less i.e., the interaction between IMP and TX-165 in different solvents was found as follows: NaCl > aqueous > urea. The fraction of TX-165 in mixed micelles (X1m) was found to be higher than IMP caused by the high hydrophobicity of TX-165 than IMP. The attained interaction parameter (βm) for bulk mixed systems was negative in each case depicting the synergism or attractive interaction amid IMP and TX-165. Numerous evaluated thermodynamic parameters demonstrated that IMP+TX-165 mixed micelles formation is viable along with spontaneous and among all employed solvents, spontaneity was found higher in NaCl solvent and lower in urea solvent than aqueous solution. Interaction of IMP with TX-165 was also detected by UV–visible analysis as an increase in absorbance was attained. Overall, results might be helpful in the development of the drug delivery system.

Two green UV-spectrophotometric techniques applying successive and progressive resolution with new concepts for simultaneous determination of completely overlapping ternary mixture

A spectrophotometric platform based on two smart techniques namely Double Divisor ratio difference spectra spectrophotometry (DDRD) and Derivative ratio amplitude difference method (DR-AD) was applied and validated. These techniques were used for determining and resolving the overlapped spectra of the 3 drugs paracetamol (PAR), pseudoephedrine (PSE) and pholcodine (PHO) in their ternary mixture. DDRD is a successive technique while DR-AD is a progressive one. In DDRD, the mixtures’ spectrum underwent division by a double divisor, and then the ratio difference method was applied. For DR-AD, consequent steps were performed to resolve each drug stepwise. DR-AD technique included division using a single divisor. The linearity ranges encompassed 5-25, 100-800 and 5-50 µg/mL for PAR, PSE and PHO, respectively. These methods were conducted according to ICH guidelines to ascertain accuracy, precision, and specificity. The analysis involved varied concentrations of drug mixtures and a pharmaceutical product. Statistical evaluation revealed no notable distinction between the suggested methodologies and those previously documented. Additionally, adherence to green analytical chemistry principles was demonstrated, establishing them as environmentally friendly analytical approaches.

Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester

The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol−1) and a relatively low melting point (∼65 °C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.

Improved Dissolution and Solubility Characteristics of Clopidogrel Bisulphate using Gelucire 44/14

Clopidogrel bisulphate is a poorly aqueous soluble drug belonging to BCS Class II. The drug is widely used to treat blood clotting in patients with peripheral, coronary, and cerebrovascular disorders, but its low bioavailability raises concern. The present study involves an effort for enhancing the solubility and drug release by transforming the drug into solid dispersions. The solid dispersions of clopidogrel bisulphate were prepared with Gelucire 44/14 using solvent evaporation method. The prepared physical mixture and solid dispersions were characterized for drug-carrier interaction, drug content, solubility, and dissolution rate. Results confirmed the increase in drug solubility with increasing polymer concentration. The dissolution profile was found to substantially improve from solid dispersion with maximum drug release in the ratio of 1:5 on comparing it with pure drug and physical mixture. FT‐IR spectra of selected solid dispersion revealed no chemical interaction between drug and polymers while the presence of the drug in the amorphous state was confirmed by DSC thermograms and X-ray diffraction, indicating better dissolution characteristics. The solid dispersions were also found to be stable under accelerated stability conditions. Keywords: Clopidogrel bisulphate, Bioavailability, Solid dispersions, Gelucire 44/14, Solubility Enhancement

Abstract 7173: Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel

Abstract Despite the success of docetaxel in combination with trastuzumab in HER2+ breast cancer, docetaxel still has serious limitations, including poor water solubility and the canonical systemic toxicity of taxanes. These side effects of taxanes need to be overcome to improve patient management. In this context, we have developed a nanoparticle drug delivery system. We have developed an immunoliposome loaded with docetaxel and grafted with trastuzumab using a microfluidic method by mixing an aqueous phase (KH2PO4 buffer) and an organic phase composed of phosphatidylcholine, cholesterol and PEGmal in a molar ratio of 50:31:1, to which docetaxel is added at a rate of 1.8% of the total lipid. We perform a thiolation reaction to graft the trastuzumab onto the polyethylene glycol chain. Resulting immunoliposomes were characterized by a mean diameter of 140 nm, a docetaxel encapsulation rate of 73% and a trastuzumab uptake rate of 400 units of trastuzumab by nanoparticle. C57BL/6 mice were administered with docetaxel 1.9 mg/kg and trastuzumab 160 ng/kg or a mixture of free drugs or as liposomes at the same dose by intraperitoneal injection. Blood was collected 1h, 2h, 3h, 6h, 8h and 24h after injection and plasma was analyzed by HPLC-UV with Paclitaxel as internal standard. For each treatment group, pharmacokinetic parameters and exposure metrics were calculated using PKanalix®: half-life T1/2, elimination rate constant Kel and area under the curve AUC at the end points (AUCtlast) and infinity (AUCinfinity). Statistical tests were performed with Sigmastats®. The results showed a marked change in pharmacokinetics with increased plasma exposure with liposomal docetaxel. Preliminary results show a longer half-life for liposomal docetaxel (40.76 h VS. 4.33 h, i.e., a 9.4-fold increase). The concentration of docetaxel appeared to decrease more rapidly between T1h and T6h with free docetaxel (Kel 0.16h-1) than with liposomal docetaxel (Kel 0.017h-1). The concentration of docetaxel reached a plateau over time, up to 24 hours (52.72± 9.45 ng/ml) in mice treated with immunoliposomes whereas Docetaxel was undetectable at T24h when treated with free drugs. There was a statistical difference in PK at T6h between liposomal docetaxel and free docetaxel, 69.86 ± 15.25 ng/ml and 53.67 ± 4.92 ng/ml, respectively (p &amp;lt; 0.001, non-paired t-test). Liposomal docetaxel showed higher AUC0-t (x3.75) and AUC0-∞ values (x5.9) compared to non-liposomal docetaxel. In conclusion, these preliminary results suggest that we have developed a promising immunoliposome for the systemic delivery of docetaxel in HER2+ breast cancer with sustained exposure. Citation Format: Mathilde Dacos, Erwan Diroff, Sarah Giacometti, Joseph Ciccolini, Raphaelle Fanciullino. Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7173.

Immobilization of Bi2MoO6/ZnO heterojunctions on glass substrate: Design of drug and dye mixture degradation by solar-driven photocatalysis

In this study, the Bi2MoO6/ZnO heterostructures were quickly and easily obtained using the sonochemical method and impregnated on a glass plate using epoxy resin. The influence of increasing the percentage of ZnO (1:1, 2:1, 4:1 and 8:1% by weight) in relation to Bi2MoO6 on the formation of the heterostructure was investigated. The XRD results of the heterostructures indicated the presence of ZnO phases with a hexagonal structure and Bi2MoO6 with an orthorhombic structure. According to FESEM and HRTEM analyses, the morphology of ZnO is controlled with the addition of Bi2MoO6. The photocatalytic activity of the heterostructures was evaluated using a mixture (MIX) of methylene blue dye and diclofenac potassium, obtaining photocatalytic efficiency of 99.7 % and 90 % in 100 min under solar irradiation, with the ZN8B1 heterostructure, respectively. Aiming to increase the reuse of the material, the ZN8B1 heterostructure was impregnated into a glass plate, obtaining an efficiency of on average 65.2 % for 10 reuse cycles, showing that the impregnate can be applied to effluent treatment. The evaluation of the effect of photocatalyst dosage, contaminant concentration and pH effect was carried out with the MIX solution in order to simulate real conditions. Furthermore, a possible photocatalytic mechanism was proposed based on inhibition tests, verifying that the •O2– and •OH radicals were the dominant active species, which followed the Z-scheme mechanism.

Toward Part-per-Million Precision in the Determination of an Ion's Collision Cross Section Using Multipass Cyclic Ion Mobility.

In cyclic ion mobility (cIMS), ions are permitted to travel multiple passes around the drift cell, increasing the distance traveled and the relative separation between ions. This study tests the hypothesis that multiple passes around the cell can also result in improved precision when measuring an ion's mobility and the collision cross section (TWCCS) derived therefrom. Experiments were performed with a diverse set of compounds, including 16 polycyclic aromatic hydrocarbons using gas chromatographic atmospheric pressure chemical ionization and a set of drug molecules by direct infusion electrospray ionization. The average periodic drift time, viz., the average time required for the ion to travel around the cIMS cell once, shifts dramatically, approaching part-per-million (ppm) precision as the number of passes increases to ∼100. Extrapolation of the precision of the CCS values with respect to the number of passes led to the prediction that the precision will reach 1000 ppm after 50 passes, 100 ppm after 100 passes, and <10 ppm after 150 passes. Experiments wherein the number of passes exceeded 100 produced TWCCS values having within-run precisions ranging between 15 and 117 ppm. The improved precision with an increasing number of passes may be a consequence of mitigating space-charge effects by allowing the ions to occupy a larger region of the cIMS cell. A method is proposed to enable practical measurements of TWCCS with ppm precision and is demonstrated to characterize an unknown drug mixture.

Beyond a spec: assessing heterogeneity in the unregulated opioid supply

BackgroundDrug checking services aim to provide compositional information for the illicit drug supply and are being employed in public health responses to extreme rates of overdose associated with fentanyl within street opioids. The technologies used within these services range from basic qualitative tests, such as immunoassay test strips, to comprehensive quantitative analyses, such as mass spectrometry. In general, there is concern that heterogeneity of a drug mixture adds significant uncertainty when using drug checking results based on a small subsamples. The presence of hot spots of active drug components in this context is often termed the ‘chocolate chip cookie effect’. Establishing the limitations of the service are essential for interpretation of the results.MethodsThis study assesses the consequence of drug heterogeneity and sampling of consumer level opioid purchased in Victoria, British Columbia (n=21\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n=21$$\\end{document}, 50–100 mg each) on quantitative fentanyl results determined from testing with paper spray mass spectrometry.Results:Using descriptive statistics, such as relative standard deviation and interquartile range, the results demonstrate varied distributions of fentanyl concentrations within a single drug batch. However, the presence of hot spots, defined as outliers, were relatively rare.ConclusionsThis study found that the variability in fentanyl concentration from drug heterogeneity and sampling is greater than that attributed to the analytical technique. On a practical level, this provides data to help guide communication of limitations of drug checking services, supporting the aim of trust and transparency between services and people who use drugs. However, if drug checking services continue to be restricted from fully engaging with the reality of manufacturing, buying, selling, mixing and dosing practices, the accuracy, usefulness, and impact will always be limited.

Improvement of an ecologically safe system of control of fungal diseases for growing on the basis of organic farming

Goal. To assess the level of effectiveness of the elements of control of fungal diseases in potato agrocenoses for various combinations of biofungicides with biologically active substances and fertilizers, methods of application and the reaction of potatoes of the Myroslav variety to them, for growing on the basis of organic farming.&#x0D; Methods. The following methods were used during the research: field — monitoring of the main diseases of potatoes in field experiments, crop accounting, determination of the effectiveness of combinations of biofungicides with plant growth regulators, organic and organo-mineral fertilizers; laboratory — accounting for damage to tubers by diseases, according to generally accepted methods.&#x0D; Results. In 2021—2022, the Laboratory of Immunity and Plant Protection of the Institute of Potato Breeding of the National Academy of Sciences conducted research on improving the elements of an environmentally safe system of controlling fungal diseases for cultivation based on organic farming. The research used the Myroslav variety of the institute’s selection, biopreparations with insecticidal, fungicidal and growth-regulating action, and organic and organo-mineral fertilizers. The lowest level of Alternaria development was noted in option 9 (treatment of tubers — organic fertilizer + PPR + plant treatment Bactophyt + PPR + organic and organo-mineral fertilizer), the development of the disease was 25.0%, the spread was 35.0 %, and the technical efficiency of the elements protection was 56.7%. It was established that for effective control of the development of common scab, rhizoctoniosis and fusarium dry rot, it is advisable to use a mixture of substances (PPR + organic fertilizer — treatment of tubers + biofungicide + organic and organo-mineral fertilizer + PPR — plant treatment), which significantly reduced the level of disease development tubers and limited their spread, compared to control and standards. The yield of potatoes in the variants was higher than in the control (22.5 t/ha) and was in the range of 31.1—42.0 t/ha. The level of the preserved harvest, relative to the control, was in the range of 8.6—19.5 t/ ha. The highest level of yield is 42.0 t/ha, noted in option 9 (organic fertilizer + PPR treatment of tubers + three Bactophyt plant treatments + organic and organo-mineral fertilizer + PPR) which, respectively, is 19.5 t/ha higher than the control and by 3.1 t/ha — standard.&#x0D; Conclusions. The use of tank mixtures of biofungicides with growth regulators and fertilizers significantly reduces the level of potato disease development and helps to increase the level of its yield. It has been established that the mixture of drugs (PPR + organic fertilizer — treatment of tubers + biofungicide + organic and organo-mineral fertilizer + PPR — plant treatment) is advisable to use to control the development of alternariosis, common scab, rhizoctoniosis and fusarium dry rot, since such a combination is ecologically safe for the environment, at the same time significantly reduces the level of development of fungal diseases and limits their spread, in comparison with control and standards, for growing on the basis of organic farming.

Evaluating the rate of reversal of fentanyl-induced respiratory depression using a novel long-acting naloxone nanoparticle, cNLX-NP.

Fentanyl and fentanyl analogs (F/FA) have become increasingly common adulterants in counterfeit prescription pills and illicit street drug mixtures due to their ease of synthesis and exceedingly high potency. The ongoing epidemic of fatal overdoses fueled by F/FA continues to highlight the need for longer-acting therapies than naloxone (NLX), the current gold-standard for reversing opioid overdoses, which shows limited efficacy to prevent renarcotization associated with F/FA toxicity. A novel opioid reversal agent based on covalent naloxone nanoparticles (cNLX-NP) has been shown to blunt fentanyl-induced respiratory depression out to 48 hr, demonstrating its potential therapeutic utility. The purpose of this study was to characterize how rapidly cNLX-NP reverses fentanyl-induced respiratory effects as well as the duration of its protective effects. Sprague Dawley male rats (n=6/group) were tested on an oximeter for baseline percent arterial oxygen saturation (%SaO2) challenged with 0.1 mg/kg SC fentanyl and 15min later given 10 mg/kg IM doses of NLX, nalmefene (NLMF), or cNLX-NP and continuously monitored via oximetry for 10 minutes. One week later the experiment was repeated using a 1:1 mixture of NLX:cNLX-NP as the reversal agent in the rats that previously received NLX alone. While both NLX and NLMF rapidly reversed %SaO2 to baseline within 1min, rats that received cNLX-NP did not return to >90% SaO2 levels until 9min after administration. Similarly, heart and breath rates returned to baseline within 1min of treatment with NLX and NLMF but did not return to baseline until 10 minutes after cNLX-NP administration. In contrast, NLX:cNLX-NP reversed all fentanyl-induced respiratory depressive effects within one minute. While cNLX-NP alone may not sufficiently reverse F/FA overdose in a timely manner, mixing free NLX with cNLX-NP can provide a mechanism to both rapidly reverse fentanyl-related effects and maintain extended protection against synthetic opioid toxicity. These data support further development of cNLX-NP as a fast-acting and long-lasting antidote to treat F/FA-induced respiratory depression and overdose, and potentially prevent renarcotization in humans.

Sonographic assessment of hemi-diaphragmatic palsy post brachial plexus blocks

Background and Aim: Brachial plexus blocks (BPB) are indispensable in providing surgical anaesthesia and postoperative analgesia. Although Hemi-diaphragmatic palsy (HDP) after BPB is clinically insignificant in the majority, it can cause significant physiological impairment in patients with reduced pulmonary function. Sonographic assessment of diaphragmatic function using the ABCDE approach provides accurate and quantitative information on HDP. This can be performed bedside before and after administration of the nerve block to quantify HDP. This was a prospective observational study comparing ultrasound-guided diaphragmatic thickness in two approaches of ultrasound-guided BPB. Methodology: Eighty participants receiving eitherinterscalene/supraclavicular BPB were included in this observational study. Baseline vitals, NRS score for pain and ultrasound-guided diaphragm thickness at inspiration and expiration using the ABCDE approach were noted. After 20 minutes of BPB administration, the diaphragm thickness was remeasured. Results: Eighty participants completed the study, forty from either group. Average volume of the total local anaesthetic drug mixture used was noted to be 30ml. The diaphragmatic thickness ratio in the supraclavicular group was found to decrease by 2.34% as compared to 2.39% in the interscalene group. (p-value 0.256 baseline values,0.292 for post block values) The thickness fraction was found to decrease by 9.21% in Group A as compared to 9.04% in Group B (P value 0.248 baseline values and 0.292 post-block values). There was no statistically significant difference between the diaphragm thickness in both the group'spre- and post-block, irrespective of the approach used. Conclusion: The ABCDE approach to measure diaphragm thickness can be used as a simple bedside modality to quantify the amount of HDP occurring after ultrasound-guided BPB. It is easy to learn &amp; a non-invasive modality which can be used to improve patient safety during BPB Bangladesh Journal of Medical Science Vol.23 (Special Issue) 2024 p.S101-S106

Exploring the biological diversity and source species of medicinal horseflies through metabarcoding

Horseflies from the Tabanidae family play a significant role in traditional Chinese medicine to treat various health conditions, including coronary heart disease, stroke, headaches, liver cirrhosis, psoriasis, and hepatic carcinoma. There are 27 species of Tabaninae (Tabanidae) used as medicine, and they showed high morphological similarities with those for which medicinal properties have not been reported. Nonetheless, there have been reports suggesting that medicinal crude drugs sometimes contain irrelevant or false species, impacting the drug's efficacy. In this current study, we collected 14 batches, totaling 13,528 individuals, from various provinces in China. Instead of “classic” DNA barcoding strategy, we employed a high-throughput metabarcoding approach to assess the biological composition of crude drug mixtures derived from horseflies. Our analysis identified 40 Amplicon Sequence Variants (ASVs) with similarity percentages ranging from 92% to 100% with 12 previously reported species. Species delimitation methods revealed the presence of 11 Molecular Operational Taxonomic Units (MOTUs), with ten belonging to the Tabanus genus and one to Hybomitra. Tabanus sp6 displayed the highest relative abundance, and its ASVs showed close resemblance to Tabanus pleski. Our investigations revealed that the medicinal batches were biologically composed of 6 to 12 species. Some batches contained ASVs that closely resembled species previously associated with false Tabanus species. In conclusion, our findings offer valuable insights into the biological composition of crude drugs derived from horseflies and have the potential to enhance the quality of these traditional medicines.

Solar-enhanced photodegradation of dye and drug mixture and evaluation of phytotoxicity on seed germination and growth by an eggshell HAp/Nb2O5 heterostructure

In this work, heterostructures of hydroxyapatite (HAp) and Nb2O5 (NO) were obtained to study their photocatalytic activity under sunlight. The samples were synthesized by the microwave-assisted hydrothermal method, and the calcium precursor used to obtain HAp was obtained from an eggshell. The influence of adding NO at 10, 30 and 50% by mass on the heterostructures was evaluated. The XRD results and the functional groups present in the FTIR spectrum confirmed the presence of the two phases in the heterostructures. UV–vis spectroscopy revealed that activation was promoted by sunlight, while PL and electrochemical analyses indicated minimized recombination of the electron/hole pairs of heterostructures due to improved charge transfer. The TEM micrographs indicated interfacial contact between the two materials. The photocatalytic efficiency of the materials was studied for the degradation of methylene blue (MB), crystal violet (CV) and tetracycline (TC) under sunlight irradiation. The heterostructure with 50% NO showed better efficiency than the other combinations and was also tested for degrading the mixture (MIX) of MB, CV and TC, for which the efficiencies were 100, 98.66 and 67.33%, respectively. Furthermore, the effects of the photocalytic dosage, concentration and pH of the solution were investigated through the MIX degradation efficiency. It was possible to propose the mechanism for the photocatalytic activity of the HAp/NO heterostructure as a direct Z-schema. The reusability of the photocatalyst and the germination tests with treated water indicated that the HAp/NO heterostructure has potential application as an efficient and nontoxic alternative for the degradation of contaminants.

Preparation and Evaluation of Mouth Dissolving Tablet of Albendazole Using Different Concentrations of Super-Disintegrant

Anthelmintic medications are anticipated to act more quickly and have greater absorption. Mouth-dissolving albendazole tablets were created using a direct compression approach and a mixture of super disintegrants to accomplish rapid disintegration of the tablets in the oral cavity. The preparation of ten batches of mouth-dissolving tablets using different grades of Kollidon, crospovidone, sodium starch glycolate, and croscarmellose sodium as super disintegrants produced the greatest results. For a compatibility investigation, FTIR was used to characterize the drug and physical mixture. An optimization technique was used to forecast the most effective formulation out of all the prepared combinations. All the physical characteristics of the tablet are within the limit. All preformulation results indicated good flow properties. Disintegration time and drug content of the F4 batch were found to be 28 seconds and 95.69%, respectively. In vitro release of the drug was performed in a phosphorus buffer pH 6.8 for 40 min, in which F4 shows maximum drug release. Based on the stability studies, it was confirmed that the optimized formulation remained at accelerated stability conditions. It was discovered that the mouth-dissolving tablet exhibits effective drug release.

Developing Aptamer-Based Colorimetric Opioid Tests.

Opioids collectively cause over 80,000 deaths in the United States annually. The ability to rapidly identify these compounds in seized drug samples on-site will be essential for curtailing trafficking and distribution. Chemical reagent-based tests are fast and simple but also notorious for giving false results due to poor specificity, whereas portable Raman spectrometers have excellent selectivity but often face interference challenges with impure drug samples. In this work, we develop on-site sensors for morphine and structurally related opioid compounds based on in vitro-selected oligonucleotide affinity reagents known as aptamers. We employ a parallel-and-serial selection strategy to isolate aptamers that recognize heroin, morphine, codeine, hydrocodone, and hydromorphone, along with a toggle-selection approach to isolate aptamers that bind oxycodone and oxymorphone. We then utilize a new high-throughput sequencing-based approach to examine aptamer growth patterns over the course of selection and a high-throughput exonuclease-based screening assay to identify optimal aptamer candidates. Finally, we use two high-performance aptamers with KD of ∼1 μM to develop colorimetric dye-displacement assays that can specifically detect opioids like heroin and oxycodone at concentrations as low as 0.5 μM with a linear range of 0-16 μM. Importantly, our assays can detect opioids in complex chemical matrices, including pharmaceutical tablets and drug mixtures; in contrast, the conventional Marquis test completely fails in this context. These aptamer-based colorimetric assays enable the naked-eye identification of specific opioids within seconds and will play an important role in combatting opioid abuse.