Hydrochloride Research Articles

Self-Assembly, In Vitro Gene Transfection, and Antimicrobial Activity of Biodegradable Cationic Bolaamphiphiles.

Bolaamphiphiles or bolaforms have drawn particular interest in drug and gene delivery, and studies of bolaforms have been growing continuously. Bolaforms, due to their unique structure, exhibit specific self-assembly behavior in water. The present work aims to develop biodegradable cationic bolaforms with a better gene transfection ability. In this work, a novel cationic bolaform (Bola-1) with head groups bearing hydroxyl (OH) functionality was designed and synthesized to investigate self-assembly and gene transfection efficiency. The self-assembly behavior of Bola-1 in water was compared with that of the hydrochloride salt (Bola-2) of its precursor molecule to investigate the effect of the -OH functionality on their solution properties. Several techniques, including surface tension, electrical conductivity, fluorescence probe, calorimetry, dynamic light scattering, and atomic force microscopy, were employed for the physicochemical characterization of Bola-1 and Bola-2. Despite the presence of polar urea groups in the spacer chain, both bolaforms were found to form spherical or elongated micelles above a relatively low critical aggregation concentration (CAC). The presence of the OH group was found to significantly affect the CAC value. The results of calorimetric measurements suggested a thermodynamically favorable aggregate formation in salt-free water. Despite stronger binding efficiency with calf thymus DNA, in vitro gene transfection studies performed using adherent cell Hek 293 suggested that both Bola-1 and Bola-2 have gene transfection efficiency comparable to that of turbofectamine standard. Both bolaforms were found to exhibit significant in vitro cytotoxicity at higher concentrations. Also, the bolaforms showed beneficial antibacterial activity at higher concentrations.

Thienylpicolinamidine derivatives as new dissolution inhibitors for carbon steels in HCl medium: experimental and theoretical studies

Abstract One of the main ways that metallic materials lose their useful qualities is through dissolution; hence corrosion management is crucial for protecting the metal. In this paper, new thienylpicolinamidine derivatives, namely; 5-[5-(3,4,5-trimethoxyphenyl)thiophen-2-yl]picolinamidine hydrochloride salt (MA-1517), 5-[5-(4-methoxyphenyl)thiophen-2-yl]picolinamidine hydrochloride salt (MA-1543), and 5-[5-(3-chloro-4-methoxyphenyl)thiophen-2-yl]picolinamidine hydrochloride salt (MA-1516), were utilized as corrosion inhibitors for C-steel in 1.0 mol L−1 HCl. Their corrosion inhibiting impact can be demonstrated by experimental methods as chemical approaches (mass reduction) and electrochemical techniques (electrochemical impedance examination, EIS, and Tafel polarization). These methods gave inhibition efficiencies (IE%) of 97.41 %, 93.84 % and 91 % for MA-1517, MA-1543 and MA-1516, respectively at 323 K and concentration 17 × 10−6 mol. L−1. The rise in IE% with rising inhibitor concentration and temperature illustrate that the adsorption of these studied compounds is chemisorption, declared via the Langmuir isotherm. Thermodynamic and kinetic parameters are computed and discussed. Polarization research exhibits that these thienylpicolinamidines act as mixed type inhibitors. The outer part morphology of C-steel surfaces and the adsorption of these compounds on C-steel outer part can be checked by atomic force microscopy (AFM), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX). The mechanism of inhibition can be backed by quantum chemical examination and Monte Carlo model. A theoretical estimate proves that the use of cationic derivatives of pyridine is good impediments versus corroding of C-steel in HCl medium.

Detection and Identification of an Unknown Impurity in Ephedrine HCl 5mg/mL Cyclic Olefin Syringes: Formulation Development.

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5mg/mL prefilled sterilized syringes after 4months of storage in the dark at room temperature (20°C ± 5°C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9months gathered already.

The free hydralazine anti-hypertensive drug and new salts with improved solubility

Although long used as an antihypertensive drug because of its vasodilator properties, Hydralazine (HDZ) has received renewed attention in the last few years due to its secondary therapeutic effects, which has led to its repurposing for its antioxidative, anti-apoptotic, and anti-inflammatory abilities, especially in cardiovascular and renal diseases. Given the worldwide prevalence of these diseases and that only the hydrochloride salt form of this drug has been reported and commercialized until now, in this paper we describe the synthesis, crystalline structure and physicochemical properties of the free hydralazine and its two new salts, a bromide (HDZ-Br) and a nitrate (HDZ-NO3), aiming to provide new candidates of HDZ solid forms that can be potentially used as an alternative to the pattern antihypertensive treatment, with better properties than the commercial one and can also be used in new applications addressed to this drug. Herein we investigated the three new multicomponent solid forms using single crystal X-ray diffraction (SCXRD), X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA), Infrared/Raman spectroscopies, and relative solubility studies. Interestingly, all structures showed the formation of HDZ columns intercalated with ions columns as well as a strong tendency to develop π···π stacking interactions among HDZ molecules which can be useful for future design of new potential multicomponent forms of HDZ. The new reported salts show a relative solubility higher than the commercially hydralazine hydrochloride form, suggesting that they can be potentially useful in new pharmaceutical formulations.

Evaluation of the In Vitro Antifungal Activity of Novel Arylsulfonamides against Candida spp.

The antifungal activity of molecules belonging to the arylsulfonamide chemotype has previously been demonstrated. Here, we screened arylsulfonamide-type compounds against a range of Candida spp. and further established the structure-activity relationship based on a "hit compound". A series of four sulfonamide-based compounds, N-(4-sulfamoylbenzyl) biphenyl-4-carboxamide (3), 2,2-diphenyl-N-(4-sulfamoylbenzyl) acetamide (4), N-(4-sulfamoylphenethyl) biphenyl-4-carboxamide (5) and 2,2-diphenyl-N-(4-sulfamoylphenethyl) acetamide (6), were tested against the American Type Culture Collection (ATCC) and clinical strains of C. albicans, C. parapsilosis and C. glabrata. Based on the fungistatic potential of prototype 3, a further subset of compounds, structurally related to hit compound 3, was synthesized and tested: two benzamides (10-11), the related amine 4-[[(4-4-((biphenyl-4-ylmethylamino)methyl) benzenesulfonamide (13) and the corresponding hydrochloride, 13.HCl. Both amine 13 and its hydrochloride salt had fungicidal effects against Candida glabrata strain 33 (MFC of 1.000 mg/mL). An indifferent effect was detected in the association of the compounds with amphotericin B and fluconazole. The cytotoxicity of the active compounds was also evaluated. This data could be useful to develop novel therapeutics for topical use against fungal infections.

Experimental and computational approaches of methoxy naphthylbithiophene derivatives and their use as corrosion protection for carbon steel in acidic medium

The inhibition efficiency and adsorption affinity were investigated for two novel compounds, namely: 6-methoxy-2-naphthyl-[2, 2’-bithiophene]-5-carboxamidine hydrochloride salt (MA-1440) and 5'-(4-chlorophenyl)-2, 2’-bifuran-5-carboxamidine hydrochloride salt (MA-1456). The inhibition study was conducted on carbon steel surface in 1.0 M HCl with different inhibitor doses and different temperature levels, to investigate the optimum dose and preferable temperature. The performed investigation included chemical, electrochemical, instrumental, and quantum computation techniques. A chemical technique was accomplished by using weight-loss measurements. Different factors were studied using weight-loss measurements in order to reach the maximum inhibition efficiency. The adsorption study revealed that the examined inhibitors obey the Langmuir adsorption isotherm and are chemically adsorbed on the steel surface. The electrochemical measurements were accomplished through the electrochemical impedance (EIS) and potentiodynamic polarization (PDP) techniques. Based on the electrochemical measurements, the examined compounds were categorized as mixed inhibitors. The instrumental examination using different techniques namely: scanning electron microscope (SEM), energy dispersive X-ray (EDX), Fourier-transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) confirmed that the considered inhibitors are excellently adsorbed over the carbon steel surface. The extent of the adsorption affinity of these compounds on the carbon steel surface was studied theoretically using quantum computations and Monte Carlo simulation. The theoretical investigation results of quantum chemistry were validated with those obtained by chemical and electrochemical methodologies. All investigations prove that, the tested compounds were adsorbed chemically on the steel surface and achieved maximum inhibition efficiency of, 94.69% and 90.85% for M-1440 and MA-1456, respectively, at the optimum concentration 30 times 10–6 mol L−1 and temperature 328 K.

Exploring the Efficacy and Safety of Levamisole Hydrochloride against Microcotyle sebastis in Korean Rockfish (Sebastes schlegelii): An In Vitro and In Vivo Approach.

Parasitic infections pose significant challenges in aquaculture, and the increasing resistance to conventional anthelmintics necessitates the exploration of alternative treatments. Levamisole hydrochloride (HCl) has demonstrated efficacy against monogenean infections in various fish species; however, research focused on Microcotyle sebastis infections in Korean rockfish (Sebastes schlegelii) remains limited. Therefore, this study aimed to evaluate the efficacy of levamisole HCl against M. sebastis infections in Korean rockfish with the goal of optimizing anthelmintic usage in aquaculture. In this study, we first assessed the susceptibility of M. sebastis to levamisole HCl in vitro. Subsequently, in vivo evaluations were conducted to assess the drug's efficacy, safety, and to identify optimal administration methods. In vitro experiments revealed concentration-dependent sensitivity of M. sebastis to levamisole HCl, with a minimum effective concentration (MEC) of 100 mg/L. In vivo experiments employed oral administration, intraperitoneal injection, and immersion treatments based on the MEC. Oral administration proved to be a safe method, yielding efficacy rates of 27.3% and 41.6% for 100 mg/kg and 200 mg/kg doses, respectively, in contrast to the immersion and injection methods, which induced symptoms of abnormal swimming, vomiting, and death. Biochemical analyses conducted to assess the safety of levamisole HCl revealed a transient, statistically significant elevation in the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) on day three post-administration at 20 °C. Following this, no substantial differences were observed. However, at 13 °C, the enzyme levels remained relatively consistent, emphasizing the role of water temperature conditions in influencing the action of levamisole HCl. Our research findings substantiate the efficacy of levamisole HCl against M. sebastis in Korean rockfish, underscoring its potential for safe oral administration. These results provide valuable insights for developing parasite control strategies involving levamisole HCl in Korean rockfish populations while minimizing adverse impacts on fish health and the environment. However, this study bears limitations due to its controlled setting and narrow focus. Future research should expand on these findings by testing levamisole HCl in diverse environments, exploring different administration protocols, and examining wider temperature ranges.

Transcriptional analysis of the molecular mechanism underlying the response of Lactiplantibacillus plantarum to lactic acid stress conditions

Lactic acid bacteria (LAB) present various benefits to humans; they play key roles in the fermentation of food and as probiotics. Acidic conditions are common to both LAB in the intestinal tract as well as fermented foods. Lactiplantibacillus plantarum is a facultative homofermentative bacterium, and lactic acid is the end metabolite of glycolysis. To characterize how L. plantarum responds to lactic acid, we investigated its transcriptome following treatment with hydrochloride (HCl) or dl-lactic acid at an early stage of growth. Bacterial growth was more attenuated in the presence of lactic acid than in the presence of HCl at the same pH range. Bacterial transcriptome analysis showed that the expression of 67 genes was significantly altered (log2FC > 2 or < 2). A total of 31 genes were up- or downregulated under both conditions: 19 genes in the presence of HCl and 17 genes in the presence of dl-lactic acid. The fatty acid synthesis-related genes were upregulated in both acidic conditions, whereas the lactate racemization-related gene (lar) was only upregulated following treatment with dl-lactic acid. In particular, lar expression increased following l-lactic acid treatment but did not increase following HCl or d-lactic acid treatment. Expression of lar and production of d-lactic acid were investigated with malic and acetic acid; the results revealed a higher expression of lar and production of d-lactic acid in the presence of malic acid than that in the presence of acetic acid.

Therapeutic effects of axitinib, an anti-angiogenic tyrosine kinase inhibitor, on interstitial cystitis

To investigate the therapeutic effects of axitinib, a tyrosine kinase inhibitor, in an interstitial cystitis (IC) rat model. IC patients with or without Hunner lesion and non-IC controls were enrolled (n = 5/group). Bladder tissues were stained with vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), platelet-derived growth factor (PDGF), and PDGF receptor B (PDGFR-B). The IC group showed extensive VEGFR-2 and PDGFR-B staining compared with controls. Next, ten-week-old female Sprague Dawley rats were divided into three groups (n = 10/group): sham, hydrochloride (HCl), and axitinib groups. One week after HCl instillation (day 0), the axitinib group received oral axitinib (1 mg/kg) for five consecutive days and pain was evaluated daily. Bladder function, histology and genetics were evaluated on day 7. The pain threshold significantly improved 3 days after axitinib administration. Axitinib decreased non-voiding contraction and increased the micturition interval and micturition volume and alleviated urothelial denudation, angiogenesis, mast cell infiltration, and fibrosis. HCl instillation increased the expression of tyrosine kinase receptors, including VEGFR-2 and PDGFR-B; axitinib administration inhibited their expression. Oral administration of axitinib improved pain, voiding profiles, and urothelial integrity by inhibiting angiogenesis in IC rat model. Axitinib may have potential therapeutic efficacy in IC patients.

Selectfluor-mediated chlorination and fluorination of arenes: late stage functionalization of APIs and its biological effects.

By using APIs previously recovered from expired drugs, it is shown that Selectfluor can act as a reagent for operationally simple late-stage fluorination and chlorination of electron-rich arenes under mild reaction conditions. As shown in mechanistic experiments, aromatic fluorination thereby competes with chlorine-for-fluorine exchange on Selectfluor and subsequent aromatic chlorination, whereat the chloride ions may either be provided by the hydrochloride salt of the respective API or by triethylammonium chloride. Biological testing of the fluorinated or chlorinated APIs at adrenergic, dopaminergic, muscarinergic, opioid or serotoninergic receptors demonstrated that improved binding affinities can be achieved via this straightforward strategy.

An Insight into the Asymmetric Resolution of 1‐Aminoindane Derivatives

AbstractCompounds with 1‐aminoindane motif exhibit vital biological activities in the central nervous system. Therefore, it is very important to synthesize new compounds with this moiety and to obtain them in high enantiopurity. In this study, novel substituted 1‐aminoindane derivatives were synthesized, and their asymmetric resolutions were carried out. Accordingly, the reduction of 1‐indanones with NaBH4, conversion of alcohols to azides via an alternative Mitsunobu reaction followed by reduction of azides afforded (±)‐1‐aminoindane hydrochloride or hydrobromide salts. Amine salts were converted into their free amines by using excess amount of Et3N and then in situ occurred free (±)‐amines were reacted with (R)‐O‐acetylmandeloyl chloride to give diastereomeric mixtures. The crystallization of the diastereomeric mixtures followed by hydrolysis yielded the corresponding asymmetric amines with high enantio‐purity.

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty

IntroductionSurgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl),...

Molluscicidal and Larvicidal Potency of N-Heterocylic Analogs against Biomophalaria alexandrina Snails and Schistosoma mansoni Larval Stages.

This work describes the synthesis of quinoline-based N--heterocyclic arenes and their biological evaluation as molluscicides against adult Biomophalaria alexandrina snails as well as larvicides against Schistosoma mansoni larvae (miracidia and cercariae). Molecular docking studies were demonstrated to investigate their affinity for cysteine protease protein as an interesting target for antiparasitics. Compound AEAN showed the best docking results followed by APAN in comparison to the co-crystallized ligand D1R reflected by their binding affinities and RMSD values. The egg production, hatchability of B. alexandrina snails and ultrastructural topography of S. mansoni cercariae using SEM were assessed. Biological evaluations (hatchability and egg-laying capacity) revealed that the quinoline hydrochloride salt CAAQ was the most effective compound against adult B. alexandrina snails, whereas the indolo-quinoline derivative APAN had the most efficiency against miracidia, and the acridinyl derivative AEAA was the most effective against cercariae and caused 100% mortality. CAAQ and AEAA were found to modulate the biological responses of B. alexandrina snails with/without S. mansoni infection and larval stages that will affect S. mansoni infection. AEAA caused deleterious morphological effects on cercariae. CAAQ caused inhibition in the number of eggs/snail/week and reduced reproductive rate to 43.8% in all the experimental groups. CAAQ and AEAA can be recommended as an effective molluscicide of plant origin for the control program of schistosomiasis.

Comparative evaluation of rapidity of action of benzydamine hydrochloride 0.3% oromucosal spray and benzydamine hydrochloride 3 mg lozenges in patients with acute sore throat: A phase IV randomized trial.

Acute sore throat (ST) can occur as part of a common cold of viral origin or caused by pharyngeal bacterial pathogens. The majority of patients with acute ST complain of pain on swallowing and dry scratchiness which can have a negative impact on the quality of life (QoL). This study aimed to evaluate the time to pain relief in patients with acute ST, following a single administration of benzydamine hydrochloride (HCl) 0.3% oromucosal spray or benzydamine HCl 3 mg lozenges. This multicenter, randomized, active-controlled, open label, parallel-group, international phase IV study was conducted at 12 investigational centers in Poland, Hungary, and Russian Federation. The study population consisted of 363 adult patients with recent onset (≤3 days) of ST and a diagnosis of tonsillopharyngitis. The primary endpoint was to assess the efficacy of benzydamine HCl in ST pain relief at 2 minutes after a single-dose administration. Secondary endpoints included, among others, the assessment of a first perceived ST relief at 1 minute after a single-dose administration of benzydamine HCl spray or lozenge. Both the spray and lozenges are effective in providing a ST relief starting already at 2 minutes after a single administration, with an effect lasting up to up to 4 hours. Clinical efficacy after 7 days of treatment and a good safety profile were also demonstrated. Anesthetic and analgesic properties of benzydamine spray and lozenges effectively addressed the patient priority of a rapid relief of symptoms of upper respiratory tract infections (URTI).

Unprecedented Route to Amide-Functionalized Double-Decker Silsesquioxanes Using Carboxylic Acid Derivatives and a Hydrochloride Salt of Aminopropyl-DDSQ.

An easy, efficient, and scalable synthetic procedure is described to obtain novel amide-functionalized double-decker silsesquioxanes (DDSQs). The use of mild conditions of deprotection of the BOC group, which does not result to the cleavage of the cage-like silsesquioxane structure, is reported. This method leads to the so far undescribed hydrochloride salt of aminoalkyl-DDSQ. Interestingly, the cis/trans-isomerization of DDSQ molecules was observed during the reaction. The resulting compounds are characterized using multinuclear NMR (1H, 13C, and 29Si), MALDI-TOF, FT-IR, and elemental analysis. Moreover, crystal structures are reported for three trans DDSQs. The chloride salt of aminoalkyl derivative, obtained in one of the steps of the synthetic pathway, shows an intriguing structure of the crystal lattice in which large channels are present, caused by ionic interactions in the lattice. The described approach opens the way to synthesizing new DDSQ derivatives and materials using BOC-blocked amines. We believe our findings would advance investigations about new materials based on little known organic-inorganic DDSQ-based hybrids.

OBTAINING OXYTETRACYCLINE CONJUGATES WITH PROTEIN CARRIERS

Oxytetracycline is widely used in veterinary medicine for the treatment of animals, as well as growth promoters. They can have adverse effects on human health through animal products if the rules for the use of antibiotics are not followed. The World Health Organization has established maximum residue limits of antibiotics in milk and meat, which require accurate, rapid and inexpensive methods to determine. Immunochromatographic assay (ICA) is ideal for this purpose due to its speed of analysis, high sensitivity and ease of use. This paper describes the results of study on the obtaining an oxytetracycline (OTC) conjugate with bovine serum albumin (BSA) and/or ovalbumin (OVA). OTC has been chemically purified from the antibiotic hydrochloride salt (OTC HC), which is widely used in animal husbandry and is more affordable than its chemically pure analogue. Spectrophotometric analysis of the prepared conjugates and immunization of laboratory animals showed the suitability of OTC, chemically purified from OTC HC, for crosslinking into BSA and/or OVA molecules and obtaining hapten-specific antibodies. The results obtained could be used for the manufacture of ICA components - labeled OTC-specific antibodies and test line antigen.

The development of an in-situ biopolymer-based floating gel for the oral delivery of metformin hydrochloride

Diabetes remains a global public health threat because of its increasing prevalence and mortality, especially in people under the age of 25. Metformin hydrochloride (HCl), as recommended by American Diabetes Association in 2022, is the first-line therapy for type 2 diabetes in adults. Metformin has low oral bioavailability due to poor permeability. Therefore, by developing metformin HCl oral in situ gel, sustained delivery of metformin can be achieved, thus enhancing the absorption of the drug. Sodium alginate and pectin were used for formulating the system. Different adjuvant polymers, including HPMC K4M, HPMC K100 LV, PEG 4000, and SCMC were used as released-pattern-modifying agents. All formulations could afloat in 0.1 N HCl at the pH of 1.2 within a minute and stay afloat for over 8 h. The optimized formulation could be made from either sodium alginate (2%) and HPMC K4M (0.5%) or pectin (2%) and HPMC K4M (2%). The optimized formulations gradually released metformin HCl with a cumulative release of 80% within 8 h. We successfully developed floating in situ gels that can release metformin HCl sustainedly.

Characterization of the hydrochloride salt hemihydrate as a new salt of the antifungal agent tioconazole

Tioconazole is an effective antifungal agent, which has a very low solubility in aqueous media, that limits its bioavailability and efficacy. In an effort to overcome the drug limitations by improving its solubility, the hydrochloride salt was prepared in methanolic 1 M HCl and obtained as the hemihydrate, as demonstrated by elemental analysis. Single crystals were grown by slow evaporation from an aqueous 1 M HCl solution and their structure was determined using single-crystal X-ray diffraction at 302 K. The structures resulting from dehydration and further rehydration were also assessed, at 333 and 283 K, respectively. The morphology of the crystal, which exhibited birefringence under polarized light, was verified by hot stage microscopy. The solid was characterized by additional means, including thermal analysis (melting point, differential scanning calorimetry and thermogravimetry), spectroscopic methods (mid infrared, near infrared, 1H, 13C and 15N nuclear magnetic resonance in solution, as well as 13C and 15N solid state with spinning at the magic angle) and X-ray diffraction techniques. Functional evaluation tests, including the intrinsic dissolution rate and the dissolution of powders were also performed. In the intrinsic dissolution rate test, the salt proved to dissolve over 2000 times faster than tioconazole. The results suggest that the new salt has physicochemical and performance properties which may support its use as a replacement of the free base in certain applications, especially where improved dissolution rate, solubility or bioavailability of the drug would be desired.

Preparation and Characterization of Chitosan coated alginate and carrageenan beads Loaded with Venlafaxine HCl: A Comprehensive Study

This study focuses on the development of microsphere systems for the sustained release of Venlafaxine Hydrochloride (HCl) using the ionotropic gelation method with sodium alginate, chitosan, carrageenan and calcium chloride as key components. The microspheres were characterized for their size, shape, and surface morphology using scanning electron microscopy (SEM). X-ray powder diffraction analysis (X-RD) was employed to determine the physical state of the drug within the formulations, while Fourier-transform infrared spectroscopy (FTIR) was used to investigate the drug-polymer interactions. Additionally, entrapment efficiency, in vitro release, and release kinetics were evaluated.The results of FTIR analysis indicated no significant interactions between the drug and polymers, ensuring the stability of the formulated microspheres. X-RD analysis confirmed the presence of the drug in an amorphous state within the beads, facilitating its sustained release. Furthermore, the absence of significant drug-polymer interactions, as indicated by FTIR analysis, supports the stability and integrity of the formulated beads. In conclusion, the developed microsphere systems demonstrate promising potential for the sustained release of Venlafaxine HCl. Their high entrapment efficiency, controlled release rate, and stability make them viable option for improving the therapeutic efficacy and patient compliance associated with Venlafaxine HCl administration. Further studies are warranted to evaluate their pharmacokinetic and pharmacodynamic profiles, as well as their long-term stability, to ensure their suitability for clinical applications.

Triethylenetetramine (TETA)

The WEEL for triethylenetetramine (TETA; CAS No. 112-24-3) was originally established in 1991 and updated in 1998 and 2009. Recent literature searches to identify new toxicity information were performed in 2016 and January 2021. No new studies or data relevant to the WEEL were identified. TETA is used in manufacturing; the hydrochloride salt of TETA is used as a copper-chelating drug in the treatment of Wilson's disease. TETA is severely irritating to the skin and eyes and produces skin sensitization; however, it is of low to moderate acute toxicity via the oral and dermal routes of exposure. In subchronic studies, signs of toxicity included multi-organ effects (lung, liver, and spleen) in mice, but not rats. TETA was genotoxic/mutagenic in short-term in vitro assays but not in in vivo assays. No data on reproductive toxicity were available. Embryo/fetal toxicity occurred at maternally toxic doses and was associated with copper deficiency. In humans, the use of TETA·2HCl for treatment of Wilson's disease during pregnancy resulted in no miscarriages or fetal abnormalities. No evidence of carcinogenicity was noted in a lifetime dermal study in mice. Based on a subchronic drinking water study in mice, 600 ppm (95mg/kg-day) was determined to be the no-observed-adverse-effect level (NOAEL) and the point of departure (POD). This NOAEL was converted to an equivalent inhalation concentration by adjusting for respiratory rate, interindividual variability, and uncertainty. The resulting 8-h time-weighted average WEEL value of 1 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to airborne TETA.