Drug Research Articles

Heterogeneous Photocatalytic Degradation of Selected Pharmaceuticals and Personal Care Products (PPCPs) Using Tungsten Doped TiO2: Effect of the Tungsten Precursors and Solvents

Pharmaceuticals and personal care products (PPCPs) which include antibiotics such as tetracycline (TC) and ciprofloxacin (CIP), etc., have attracted increasing attention worldwide due to their potential threat to the aquatic environment and human health. In this work, a facile sol-gel method was developed to prepare tungsten-doped TiO2 with tunable W5+/W6+ ratio for the removal of PPCPs. The influence of solvents in the synthesis of the three different tungsten precursors doped TiO2 is also taken into account. WCl6, ammonium metatungstate (AMT), and Na2WO4●2H2O not only acted as the tungsten precursors but also controlled the tungsten ratio. The photocatalyst prepared by WCl6 as the tungsten precursor and ethanol as the solvent showed the highest photodegradation performance for ciprofloxacin (CIP) and tetracycline (TC), and the photodegradation performance for tetracycline (TC) was 2.3, 2.8, and 7.8 times that of AMT, Na2WO4●2H2O as the tungsten precursors and pristine TiO2, respectively. These results were attributed to the influence of the tungsten precursors and solvents on the W5+/W6+ ratio, sample crystallinity and surface properties. This study provides an effective method for the design of tungsten-doped TiO2 with tunable W5+/W6+ ratio, which has a profound impact on future studies in the field of photocatalytic degradation of PPCPs using an environmentally friendly approach.

Three‐step integrated process for isolation and purification of impurities in drug substance by recycling chromatography

AbstractThis work reported the application of a twin‐column recycling chromatography system for the separation of three minor impurities in crude aloe‐emodin. The whole process went through three steps, each using a different mobile phase to separate corresponding impurity, which were integrated and automatically operated in a single device. Despite these impurities peaked closely in high‐performance liquid chromatography, they were successfully purified to a content exceeding 97%. In addition, the lab‐scale separation could reach the yields at the mg‐level. The high efficacy should be mainly attributed to the introduction of a small step solvent gradient between the upstream and downstream columns, which helped to counterbalance the band broadening. This report suggested that such an automated chromatographic system could provide fast and accurate separation of multiple impurities, allow the process of high‐throughput samples, and reduce the time required for purification and recovery of minor impurities in drugs.

Rice (Oryza sativa) Stem Cells as a Novel Promising Active Ingredient with Anti-Proliferative Effects for Potential Skin Cancer Prevention and Skin Whitening Activity

Rice is one of the plants proven to possess antioxidant, anti-inflammatory, anti-proliferative, and whitening properties, making it one of the most beneficial plants in this regard. This study aimed to introduce a novel natural cosmetic and pharmaceutical product based on rice callus as a source of active ingredients that can inhibit skin melanoma cell (B16F10) proliferation and brighten the skin. The 2,4-D hormone at concentrations of 1 µg/mL and 1.5 µg/mL was used to induce rice callus formation. Rice callus extracts were then prepared using aqueous and ethanolic solvents, with a concentration of 1 mg/mL used for characterization tests. To determine the optimal hormone concentration, the phenols/flavonoids, antioxidant activity, proteins, and carbohydrates in the extracts were measured. The optimal concentration of the hormone was found to be 1 µg/mL. Finally, the anti-melanocyte and skin-whitening activity of the extracts was assessed through measurements of their cytotoxicity and inhibition of melanin synthesis-related enzymes. Cellular cytotoxicity measurements revealed that the ethanolic extract induced more cytotoxicity than the aqueous extract, with IC50 values of 566.3 µg/mL for the ethanolic extract and 1327 µg/mL for the aqueous extract. Skin-whitening-related tests demonstrated that the extracts were 1.7 times more effective than arbutin in inhibiting factors that cause hyperpigmentation. The aqueous extract achieved 85% inhibition of melanin biosynthesis at a concentration of 3200 µg/mL, compared to 68% for the ethanolic extract and 50% for arbutin. Based on these findings, rice callus extract can be introduced as a new, effective substance for skin-lightening and anti-melanocyte products in cosmeceutical and pharmaceutical formulations.

Contextualising Experiences of Co-Occurring Mental Ill-Health and Substance Use Among Trans, Non-Binary, and Gender Diverse Young People: Implications for Tailored Harm Reduction Approaches.

Though significant research highlights higher rates of mental ill-health and substance use among trans, non-binary and gender diverse (henceforth 'trans') young people, little research has considered patterns, contextual characteristics, and correlates of co-occurring experiences of mental ill-health and substance use among trans young people. Using data from the Trans Pathways study, we used prevalence ratios and age- and gender-adjusted logistic regression models to examine prevalence and differences of co-occurring substance use (past six-month cigarette use, alcohol use, and other drug use) and contextual characteristics of substance use (past six-month solitary alcohol and/or drug use, substance use for coping) by mental ill-health (depression disorder, anxiety disorder, past 12-month self-harm thoughtsand behaviours,suicidal thoughts, planning, and attempt/s). Age- and gender-adjusted models assessed associations between co-occurring depressive and anxiety disorders and recent cigarette, alcohol, and other drug use (six co-occurring items total) and 18 interpersonal stressors. Significantly increased odds of smoking or recentuse of cannabis or sedatives was observed among trans young people reporting depressive disorder, anxiety disorder (aORs ranging 1.8-3.1). Trans young people who reported recent smoking or use of cannabis, inhalants, or sedatives, had 40% to 80% reduced odds of past 12-month self-harm thoughts, self-harm behaviours,suicidal thoughts, and suicide attempt/s (aORs ranging 0.2-0.6). On the other hand, solitary alcohol and/or other drug use and substance use for coping was significantly associated with increased odds of all mental ill-health outcomes. Issues with school, secure housing, and intimate partner abuse were themost robust correlates of co-occurring mental ill-health and substance use. Trans young people using substances, especially cigarettes, cannabis, and sedatives, often so do with co-occurring experiences of depression and anxiety though limited substance use in more 'social' contexts may confer benefits for preventingself-harm and suicide thoughts and behaviours. Continued research in partnership with trans young people is warranted to conceptualise more nuanced and precise conceptualparameters of trans-affirming substance useharm reduction approaches.

Understanding the mechanisms of food effect on omaveloxolone pharmacokinetics through physiologically based biopharmaceutics modeling.

Omaveloxolone is a nuclear factor (erythroid-derived 2)-like 2 activator approved in the United States and the European Union for the treatment of patients with Friedreich ataxia aged ≥16 years, with a recommended dosage of 150 mg orally once daily on an empty stomach. The effect of the US Food and Drug Administration (FDA) high-fat breakfast on the pharmacokinetic profile of omaveloxolone observed in study 408-C-1703 (NCT03664453) deviated from the usual linear correlation between fed/fasted maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) ratios reported for various oral drugs across 323 food effect studies. Here, physiologically based biopharmaceutics modeling (PBBM) was implemented to predict and explain the effect of the FDA high-fat breakfast on a 150-mg dose of omaveloxolone. The model was developed and validated based on dissolution and pharmacokinetic data available across dose-ranging, food effect, and drug-drug interaction clinical studies. PBBM predictions support clinical observations of the unique effect of a high-fat meal on omaveloxolone pharmacokinetic profile, in which the Cmax increased by 350% with only a 15% increase in the AUC. Key parameters influencing omaveloxolone pharmacokinetics in the fasted state based on a parameter sensitivity analysis included bile salt solubilization, CYP3A4 activity, drug substance particle size distribution, and permeability. Mechanistically, invivo omaveloxolone absorption was solubility and dissolution rate limited. However, in the fed state, higher bile salt solubilization led to more rapid dissolution with predominant absorption in the upper gastrointestinal tract, resulting in increased susceptibility to first-pass gut extraction; this accounts for the lack of correlation between Cmax and AUC for omaveloxolone.

International Workers' Day: Consumption Patterns of Morphine, Codeine, and Methamphetamine in Urban and Rural Areas Based on Wastewater-Based Epidemiology.

Wastewater-based epidemiology (WBE) is a reliable means to estimate drug consumption in a specific population. By measuring the concentration of drug residues or metabolites in wastewater, the consumption behavior pattern of a specific population can be deduced. Using the WBE method, the present study, for the first time, continuously monitored the differences in the consumption of morphine (MOR), codeine (CODE), and methamphetamine (METH) in three wastewater-treatment plants in a city and two surrounding villages in Xinjiang, China during International Workers' Day and the following week. The wastewater samples were pretreated by solid-phase extraction and then analyzed by high-performance liquid chromatography-tandem mass spectrometry. Methamphetamine was not detected in rural areas and was detected only on International Workers' Day in urban areas. According to the estimation of per capita consumption, the per capita consumption of MOR, CODE, and METH in urban inhabitants was 12.04 to 23.39, 10.44 to 16.39, and 1.31 mg/day/1000 inhabitants. The per capita consumption of MOR and CODE in rural areas was 5.19 to 8.35 and 2.56 to 3.52 mg/day/1000 inhabitants. The consumption of MOR in urban and rural areas was significantly higher than that of CODE and METH. During International Workers' Day, workdays, and weekends, the consumption of MOR and CODE in urban areas is significantly higher than that in rural areas. Compared with those on weekends, the consumption of urban MOR and CODE increased more during International Workers' Day. The consumption of MOR in urban areas showed a weekend effect. The present study can provide information for subsequent research and government departments. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC.

Selective and sensitive molecularly imprinted polymer-based electrochemical sensor for detection of Deltamethrin

Electrochemical sensors have a broad range of industrial applications due to their sensitivity, speed, and cost-effectiveness. These sensors enable the continuous monitoring and control of critical parameters in various industrial processes. For instance, they are essential in food safety, environmental monitoring, biomedical applications, and pharmaceutical production. In the food industry, electrochemical sensors facilitate the rapid and reliable detection of contaminants and pathogens in food products, thus enhancing product quality and consumer safety. An electrochemical sensor was developed with the molecularly imprinted polymer (MIP) technique to detect deltamethrin with high sensitivity and selectivity. The sensor was fabricated by electrodeposition of Co3O4 on indium tin oxide (ITO), followed by electropolymerization of o-phenylenediamine with deltamethrin as a template molecule. The template molecules were then removed from the modified electrode by a methanol. The MIP-based electrochemical sensor exhibited high sensitivity and selectivity towards deltamethrin. Under the optimized conditions, the LOD values for the MIP/Co3O4/ITO electrode in the first and second linear regressions were 1.53 nM for linear range of 2.82 nM to 56.5 nM and 0.34 μM for linear range of 0.25 μM to 3.98 μM. Moreover, the LOD values for the NIP/Co3O4/ITO electrode in the first and second regressions were 2.43 nM for the linear range of 3.91 nM to 65.0 nM and 726.0 nM for the linear range of 0.023 μM to 4.5 μM. The developed electrochromic pesticide sensor, being an electrochemical-based molecularly imprinted polymer (MIP) sensor incorporating electrochromic materials, enables both target-specific pesticide detection and visual pesticide identification based on color changes dependent on pesticide concentration. Consequently, this system is more advantageous compared to electrochemical-based MIP sensors, as it provides both qualitative and quantitative determinations. The qualitative assessment aims to enhance the ease of use of the sensor, thereby increasing the potential for it to become a commercially viable product by reducing the need for instrumental devices.

Highly Efficient Production of Furfural from Corncob by Barley Hull Biochar-Based Solid Acid in Cyclopentyl Methyl Ether–Water System

Furfural, an important biobased compound, can be synthesized through the chemocatalytic conversion of D-xylose and hemicelluloses from lignocellulose. It has widespread applications in the production of valuable furans, additives, resins, rubbers, synthetic fibers, polymers, plastics, biofuels, and pharmaceuticals. By using barley hulls (BHs) as biobased support, a heterogeneous biochar Sn-NUS-BH catalyst was created to transform corncob into furfural in cyclopentyl methyl ether–H2O. Sn-NUS-BH had a fibrous structure with voids, a large comparative area, and a large pore volume, which resulted in more catalytic active sites. Through the characterization of the physical and chemical properties of Sn-NUS-BH, it was observed that the Sn-NUS-BH had tin dioxide (Lewis acid sites) and a sulfonic acid group (Brønsted acid sites). This chemocatalyst had good thermostability. At 170 °C for 20 min, Sn-NUS-BH (3.6 wt%) was applied to transform 75 g/L of corncob with ZnCl2 (50 mM) to generate furfural (80.5% yield) in cyclopentyl methyl ether–H2O (2:1, v/v). This sustainable catalytic process shows great promise in the transformation of lignocellulose to furfural using biochar-based chemical catalysts.

S11-04 Derisking cardiovascular safety throughout the pharmaceutical product lifecycle

S11-04 Derisking cardiovascular safety throughout the pharmaceutical product lifecycle

Block Chain Technology in the Pharmaceutical Supply Chain: Enhancing Transparency and Security

Blockchain technology has been a key addition to the technology sector and its integration to various aspects of businesses has achieved immense success. Its implementation in the pharmaceutical industry continues to give promise of further optimizing the supply chain by increasing safety, efficiency, and transparency. This paper explores the fundamental concepts of Blockchain technology and its relevance to supply chain management, particularly within the pharmaceutical industry. It examines how Blockchain enhances transparency through real-time tracking and traceability of pharmaceutical products, thereby mitigating risks associated with counterfeiting and unauthorized distribution. This research will also look at various successful projects that have embraced the Blockchain technology such as the IBM and Walmart's Blockchain pilot and the Medi Ledger Project. It also highlights the challenges that companies need to address in the future so as to be able to successful implement the system. Overall, the research into how Blockchain technology is able to offer security and efficiency in the pharmaceutical supply chain is presented herein

Impact of reduced sampling frequency of illicit drug wastewater monitoring in the Netherlands

Drug consumption estimates are traditionally based on surveys or information from police seizures. Alternatively, residues of illicit drugs in untreated wastewater (influent) can be used to calculate mass loads and subsequently estimate drug consumption in the community throughout the week. For this purpose, wastewater is commonly sampled for seven consecutive days within the Sewage analysis CORe group Europe (SCORE), while other sampling schemes may be implemented in long-term studies outside this consortium. The current study demonstrates how sampling frequency of illicit drug residues in the influent of wastewater treatment plants (WWTPs) affects the derived weekly average. Thirty WWTPs were sampled over the course of 12 years and influents were analyzed for five drugs (metabolites): 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, amphetamine, benzoylecgonine (a metabolite of cocaine), and 11-nor-9-Carboxy tetrahydrocannabinol (THC-COOH). Subsequently, small and large WWTPs were grouped with a threshold of 100,000 inhabitants. After data curation, standardized loads were calculated (mg/d per 1000 inhabitants). Weekly averages of loads of the drug residues were calculated based on six scenarios (sampling one to six weekdays) and compared to the weekly average in the control situation (sampling seven weekdays) in a Monte Carlo simulation. Results indicate that drug residues with more dynamic loads over a week require more frequent sampling. The analysis illustrates that a decreased sampling frequency (4 or 5 days per week) still leads to a representative weekly average for all drugs tested when a deviation up to a factor of 1.25 is deemed acceptable. However, knowledge on typical levels is necessary to define outliers. We therefore recommend to study dynamics in drug residue loads for WWTPs before reducing sampling frequency in long term monitoring programs.

Concentrations, Partitioning and Ecological Risk of Pharmaceuticals and Personal Care Products in UK Freshwater Sediment

Pharmaceuticals and personal care products (PPCPs) have received increasing attention in recent years as emerging contaminants that could adversely affect human health and the environment. While previous studies focused mainly on water, little is known about the occurrence and risk of PPCPs in sediment. The present study investigated 30 widely used PPCPs in sediment samples from two rivers and two canals in the UK. Average Σ30PPCPs concentrations in sediments were 129, 79, 62 and 110ng/g dry weight in the River Tame, Coventry Canal, River Severn, and Birmingham & Worcester canal, respectively. Amoxicillin, gabapentin, caffeine, propranolol, DEET, naproxen, diclofenac Na, meclofenamic acid and β-estradiol were detected in all studied locations. The highest concentration measured was 43.6ng/g of diclofenac (Coventry Canal). The octanol-water partition coefficient (Log KOW) of target PPCPs, and their experimentally measured sediment–water distribution coefficient (Log KP), showed a significant positive correlation, indicating the partitioning of PPCPs between water and sediment may be attributed, at least partially, to their lipophilicity. The ecological risk of target PPCPs in sediment to aquatic biota was assessed using a risk quotient (RQ) approach. The estimated RQ values for amoxicillin on Cyanobacteria were > 1 in all studied locations, indicating high risk to freshwater Cyanobacteria, while 17-α-ethinyl estradiol and caffeine posed high ecological risk (RQ > 1) to fish. These results highlight the need for better removal efficiency of PPCPs by wastewater treatment plants to prevent their accumulation in sediment and call for further development of effect-based sediment quality standards.

Sequencing of Phosphorodiamidate Morpholino Oligomers by Hydrophilic Interaction Chromatography Coupled to Tandem Mass Spectrometry.

Sequencing of phosphorodiamidate morpholino oligomers (PMOs) by hydrophilic interaction chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) is reported. The MS/MS analysis was performed using a quadrupole/time-of-flight (Q-ToF) mass analyzer and collision induced dissociation (CID) in negative ion mode. To improve MS sensitivity in negative ion mode, HILIC conditions, including the separation column, mobile phases, and MS parameters, were optimized. Using the developed HILIC-CID-MS/MS method, 100% sequence coverage was achieved for PMOs ranging from 18-mer to 25-mer. Additionally, the method was successfully applied to identifying positional isomers of n - 1 deletion impurities present in PMO drug substances.

Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models.

Rapid Identification of Lactobacillus acidophilus and Bifidobacterium by a 16S rRNA PCR Method

Background: Probiotics are live microorganisms that, when administered, have beneficial effects on human health. Hence, various probiotic organisms belonging to the genera Lactobacillus and Bifidobacterium are being increasingly used in food and pharmaceutical products. For regulatory compliance, simple and reliable analytical methods are required for selective enumeration of different probiotic organisms present in food and pharmaceutical formulations. Objective: This study aimed to establish a rapid PCR-based method for the identification and differentiation of Lactobacillus acidophilus and Bifidobacterium strains. objective: The aim of our study is to establish a rapid PCR based method for the identification and differentiation of Lactobacillus acidophilus and Bifidobacterium strains. Methods: Species-specific and genus-specific primers for Lactobacillus and Bifidobacterium were designed based on their 16S rRNA gene sequence. Genomic DNA of different Lactobacillus and Bifidobacterium strains were subjected to PCR with annealing temperature specific for respective primer pairs. Results: Lactobacillus acidophilus primers gave positive PCR results only with Lactobacillus acidophilus strains and not with other Lactobacillus species, whereas Bifidobacterium genus-specific primers gave positive PCR results with most of the Bifidobacterium strains. Conclusion: The three species-specific L. acidophilus primer pairs and three genus-specific primer pairs of Bifidobacterium used in this study could easily identify and differentiate Lactobacillus acidophilus and Bifidobacterium with high specificity.

Eco Friendly Pharmaceutical Packaging

Abstract: Concerns over environmental contamination have been raised by the use of nonbiodegradable and non-renewable materials such as glass, plastics, and metals in packaging applications. With the goal of lessening the environmental impact of petroleum-based packaging materials, an extensive amount of research has been conducted to find alternative packaging materials. Due to their biodegradability, studies have shown that using bio-polymer-based materials can reduce the amount of packaging waste produced, which could partially address the issue of trash disposal. This review article is mainly focused on eco-friendly biodegradable material that can replace nonbiodegradable pharmaceutical packaging material. These materials come from natural resources like proteins, carbohydrates, etc. that have negligible to no negative effects on the environment and organisms that depend on it. This article depicts how we can replace the existing non-biodegradable plastics with eco-friendly material as the use of pharmaceutical packaging material also plays a crucial role in the therapeutic performance of pharmaceutical products.

An Overview of the Analytical Methods for Products based on Clindamycin and Eco-efficiency Perspectives.

Clindamycin (CLIN), an antibiotic sold in the form of capsules, injectable solution, gel, and lotion, is easily soluble in water and ethanol. However, it lacks eco-efficient methods for evaluating pharmaceutical products. The objective of this review is to provide an overview of the analytical methods present both in the literature and in official compendia for evaluating pharmaceutical matrices based on CLIN in the context of Green Analytical Chemistry (GAC). Firstly, microbiological methods for evaluating the potency of CLIN final products were not found, which already shows the need to develop new methods. Among the methods found, which are all physicalchemical, the most used method is HPLC (71%) followed by UV-Vis (14%). Among the targets of the methods, capsules and raw materials were the most studied (33% each). Among the choices of analytical conditions for the methods, acetonitrile is the preferred solvent (27.7%), even though CLIN is easily soluble in ethanol. Thus, the gap in eco-friendly and sustainable analytical methods is a reality and an opportunity for analytical development centers to provide means for evaluating the quality of CLIN-based products.

Development of a Stable Lyophilized Cyclophosphamide Monohydrate Formulation Using Non-Aqueous Solvents.

To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55°C with annealing step at -22°C by which the reconstitution time was significantly reduced. The drying was performed at below - 25°C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.

Buccal lidocaine mucoadhesive patches for pediatrics’ teething pain: overcoming possible hazards of oral gels

Objectives The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population. Methods The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing. Key findings The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects. Conclusion The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.

A novel step towards the heterologous biosynthesis of paclitaxel: Characterization of T1βOH taxane hydroxylase

In the quest for innovative cancer therapeutics, paclitaxel remains a cornerstone in clinical oncology. However, its complex biosynthetic pathway, particularly the intricate oxygenation steps, has remained a puzzle in the decades following the characterization of the last taxane hydroxylase. The high divergence and promiscuity of enzymes involved have posed significant challenges. In this study, we adopted an innovative approach, combining in silico methods and functional gene analysis, to shed light on this elusive pathway. Our molecular docking investigations using a library of potential ligands uncovered TB574 as a potential missing enzyme in the paclitaxel biosynthetic pathway, demonstrating auspicious interactions. Complementary in vivo assays utilizing engineered S. cerevisiae strains as novel microbial cell factory consortia not only validated TB574's critical role in forging the elusive paclitaxel intermediate, T5αAc-1β,10β-diol, but also achieved the biosynthesis of paclitaxel precursors at an unprecedented yield including T5αAc-1β,10β-diol with approximately 40 mg/L. This achievement is highly promising, offering a new direction for further exploration of a novel metabolic engineering approaches using microbial consortia. In conclusion, our study not only furthers study the roles of previously uncharacterized enzymes in paclitaxel biosynthesis but also forges a path for pioneering advancements in the complete understanding of paclitaxel biosynthesis and its heterologous production. The characterization of T1βOH underscores a significant leap forward for future advancements in paclitaxel production using heterologous systems to improve cancer treatment and pharmaceutical production, thereby holding immense promise for enhancing the efficacy of cancer therapies and the efficiency of pharmaceutical manufacturing.