Development Of Drug Formulations Research Articles

Dual Targeting of Prostate-Specific Membrane Antigen and Fibroblast Activation Protein: Bridging Prostate Cancer Theranostics with Precision.

Targeting Prostate Specific Membrane Antigen (PSMA) has proven highly useful and beneficial for prostate cancer (PCa) theranostics. However, patients with advanced metastatic castration-resistant prostate cancer (mCRPC) lack optimal PSMA expression resulting in poor specificity. To address this limitation, combination targeting is gaining popularity by synergistically boosting the theranostic efficacy. Herein, we thoroughly reviewed the most recent development of drug formulation for PCa theranostics by targeting both PSMA and Fibroblast Activation Protein (FAP). FAP is known to overexpress in cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME). It has been extensively studied as an effective target for the identification and treatment of a variety of cancer phenotypes. Along with the advantages and current updates on combination targeting of PSMA and FAP, this Review thoroughly discussed the expression patterns of PSMA and FAP in various cancer phenotypes, as well as their role in tumor growth, invasion, and metastasis, which is of great interest in the design and development of prostate cancer theranostics.

Green/red fluorescent protein disrupting drugs for real‐time permeability tracking in three‐dimensional tumor spheroids

AbstractThree‐dimensional (3D) spheroid models offer a more physiologically relevant and complex environment compared to traditional two‐dimensional cultures, making them a promising tool for studying tumor biology and drug response. However, these models often face challenges in real‐time monitoring of drug diffusion, penetration, and target engagement, limiting their predictive power for in vivo and clinical outcomes. This study introduces a novel approach for real‐time tracking of drug permeability using small molecule drugs with GFP/RFP‐disrupting properties that correlate with their efficacy. We developed a reproducible 3D spheroid model with various cancer cell lines expressing GFP/RFP for efficient drug screening. Through screening over 20 FDA‐approved enzyme inhibitors, we identified three covalent kinase inhibitors—osimertinib, afatinib, and neratinib—that irreversibly disrupt GFP and RFP fluorescence. Our results reveal distinct drug diffusion and penetration profiles within GFP/RFP‐expressing spheroids, varying with drug concentration and formulation, and correlating with clinical volume of distribution (Vd) values. Additionally, we demonstrate that our approach is useful for evaluating different drug formulations as well as screening penetration enhancers for solid tumors. These findings offer a valuable 3D model for studying kinetics of drug permeability and efficacy in tumor‐like environments, with potential implications for drug delivery research and formulation development.

Toward nanosuspension preparation by modeling the solubility of levofloxacin and ofloxacin in ethanol + water solvent mixtures at different temperatures

The present study was conducted to assess the solubility of levofloxacin and ofloxacin in different mono- and mixed solvent systems at different temperatures to provide an experimental basis for the preparation of levofloxacin and ofloxacin nanosuspensions. To this end, the solubility of both compounds was evaluated using a solid–liquid equilibrium technique in DMSO, acetone, ethanol, NMP, and water monosolvents and ethanol–water mixed solvents at different volume fractions and temperatures. The modified versions of the van’t Hoff and Gibbs equations were recruited to calculate the thermodynamic properties of the solutions. The correlation between the solubility data of levofloxacin and ofloxacin and different mathematical models, including the Yalkowsky, Jouyban-Acree, and van’t Hoff models and their combinations was studied. According to the results, the highest and lowest solubility of levofloxacin and ofloxacin were attainable in 1 (pure ethanol monosolvent) and 0.1 v/v of ethanol fractions in ethanol/water mixed solvent. Moreover, the solubility of both compounds was superior at higher temperatures. Afterwards, the nanosuspensions were prepared using the solvent-antisolvent method. Different characterization techniques revealed the formation of the smallest particles with relatively irregular morphology in the 0.1 v/v volume fraction of ethanol in water. The XRD analysis exhibited the typical crystalline diffractions of levofloxacin and ofloxacin and the thermal transitions and stability of both compounds were investigated using DSC and TGA techniques. The results obtained in this study could be used to enhance the solubility and bioavailability of levofloxacin and ofloxacin during the drug formulation development and manufacturing processes.

Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.

Glioblastoma is a malignant manifestation of a solid brain tumour with a very dismal prognosis due to an overall median survival of 14 months. The currently administered Standard treatment plan, the STUPP regimen, is not very effective in tackling this neoplasia. A major concern that affects the development of new drug formulations, specifically for Glioma, is the inherent sub-clonal heterogeneity, which includes the dynamic and intricate nature of the Tumour Microenvironment (TME). Targeting the cellular niche using personalized medication for glioma specifically gene therapy, seems to be promising, with most studies in preclinical models yielding optimistic results. This paper analyses the great headways made in glioma gene therapy in the last 10 years while looking into different therapeutic strategies. That said, certain challenges do plague the clinical use of gene therapy which have been highlighted in the hopes that future researchers will address these concerns and further propel gene therapy in its journey from the Lab to the bedside.

A Comprehensive Review on Imperative Role of Ionic Liquids in Pharmaceutical Sciences.

Ionic liquids (ILs) are poorly-coordinated ionic salts that can exist as a liquid at room temperatures (or <100 °C). ILs are also referred to as "designer solvents" because so many of them have been created to solve particular synthetic issues. ILs are regarded as "green solvents" because they have several distinctive qualities, including better ionic conduction, recyclability, improved solvation ability, low volatility, and thermal stability. These have been at the forefront of the most innovative fields of science and technology during the past few years. ILs may be employed in new drug formulation development and drug design in the field of pharmacy for various functions such as improvement of solubility, targeted drug delivery, stabilizer, permeability enhancer, or improvement of bioavailability in the development of pharmaceutical or vaccine dosage formulations. Ionic liquids have become a key component in various areas such as synthetic and catalytic chemistry, extraction, analytics, biotechnology, etc., due to their superior abilities along with highly modifiable potential. This study concentrates on the usage of ILs in various pharmaceutical applications enlisting their numerous purposes from the delivery of drugs to pharmaceutical synthesis. To better comprehend cuttingedge technologies in IL-based drug delivery systems, highly focused mechanistic studies regarding the synthesis/preparation of ILs and their biocompatibility along with the ecotoxicological and biological effects need to be studied. The use of IL techniques can address key issues regarding pharmaceutical preparations such as lower solubility and bioavailability which plays a key role in the lack of effectiveness of significant commercially available drugs.

Nanotechnology in Drug Delivery: Overcoming Poor Solubility Challenges through Nanoformulations

Abstract: The pharmaceutical sector continues to face difficulties with poorly soluble drug solubility. Insufficiently soluble drugs have low bioavailability, and their effectiveness is frequently affected. Numerous approaches have been developed in response to this challenge, including using various dosage forms, solid dispersions, nano-suspensions, self-emulsifying drug delivery systems, and cyclodextrin complexes. By improving drug dissolving, decreasing drug particle size, and increasing drug dispersion, these dosage forms seek to increase drug solubility. Nanotechnology is one of the latest advances that has the potential to revolutionize the delivery of drugs and significantly improve the solubility of drugs that are now poorly soluble. Since they have a larger surface area and can pass through biological barriers, nanoparticles are particularly well suited for the delivery of drugs. These technologies can potentially enable the development of more effective and efficient drug formulations for the treatment of various diseases. In addition, the review highlights recent advances in the field, including emerging technologies such as nanotechnology, which can revolutionize drug delivery and significantly improve the solubility of poorly soluble drugs with their potential applications.

Nanotechnology in pharmaceutical manufacturing: present innovations and future opportunities

Nanotechnology has revolutionized the pharmaceutical industry by enabling the design and delivery of drugs with enhanced precision, efficacy, and safety. This review provides a comprehensive overview of current trends and future prospects in nanotechnology-based drug manufacturing. It explores the application of nanocarriers, such as liposomes, micelles, and nanoparticles, which have improved drug bioavailability, targeted delivery, and reduced side effects. Nano formulations like solid lipid nanoparticles (SLNs) and polymeric nanoparticles are also highlighted for their role in controlled drug release and cancer treatment. Technological innovations, including advanced nanofabrication techniques and 3D printing, are driving the development of complex drug formulations. The review also addresses the challenges in scaling production and the evolving regulatory landscape. Future prospects include the use of nanobots and advanced Nano machines for drug delivery, the integration of nanotechnology in gene therapy and CRISPR, and the exploration of new research and investment opportunities. Ethical and safety considerations, such as the long-term effects of nanomaterials on human health and the environment, are discussed. This review underscores the transformative potential of nanotechnology in drug manufacturing, offering insights into its role in shaping the future of the pharmaceutical industry.

MANNICH REACTION’S MESMERIZING MANIFESTATIONS

After introduction of a new natural or synthetic chemical entity as a drug, the focus of research has always shifted to the modification of this chemical entity with the objective of improving ADMET properties, formulations for its efficient delivery, solubility, stability, organoleptic properties, reduction of toxicity, expansion of pharmacological range, formation of precursors, condensation products, complexation, prevention of formation of trace impurities and more. For example, the analgesic and antipyretic drug antipyrine, one of the earliest synthetic drugs, forms an intermolecular hydrogen bond with salicylic acid to give the stable compound antipyrine salicylate, also known as salipyrin. During the development of an aqueous drug formulation containing salipyrin and hexamine, 112 years ago, the unusual formation of a precipitate after some time did not go unnoticed by the young pharmacist and chemist Carl Mannich at Berlin University. Mannich then went on to explain the possible mechanism of formation of the condensation product, later to be known as the first Mannich compound or Mannich base, in a seminal, 21-page publication along with his student Krösche. The explanation was as much brilliant as it was accurate. He recognised that it was a generally applicable reaction, which would open the doors to the then difficult-to- synthesize 1,3-ketamines and which would allow the formation of open and cyclic compounds containing nitrogen – and to the world of natural product chemistry. An artistic view of the first Mannich base, which also happened to be tris-symmetrical, is reproduced below.

Advancements and Applications of Artificial Intelligence in Pharmaceutical Sciences: A Comprehensive Review.

Artificial intelligence (AI) has revolutionized the pharmaceutical industry, improving drug discovery, development, and personalized patient care. Through machine learning (ML), deep learning, natural language processing (NLP), and robotic automation, AI has enhanced efficiency, accuracy, and innovation in the field. The purpose of this review is to shed light on the practical applications and potential of AI in various pharmaceutical fields. These fields include medicinal chemistry, pharmaceutics, pharmacology and toxicology, clinical pharmacy, pharmaceutical biotechnology, pharmaceutical nanotechnology, pharmacognosy, and pharmaceutical management and economics. By leveraging AI technologies such as ML, deep learning, NLP, and robotic automation, this review delves into the role of AI in enhancing drug discovery, development processes, and personalized patient care. It analyzes AI's impact in specific areas such as drug synthesis planning, formulation development, toxicology predictions, pharmacy automation, and market analysis. Artificial intelligence integration into pharmaceutical sciences has significantly improved medicinal chemistry, drug discovery, and synthesis planning. In pharmaceutics, AI has advanced personalized medicine and formulation development. In pharmacology and toxicology, AI offers predictive capabilities for drug mechanisms and toxic effects. In clinical pharmacy, AI has facilitated automation and enhanced patient care. Additionally, AI has contributed to protein engineering, gene therapy, nanocarrier design, discovery of natural product therapeutics, and pharmaceutical management and economics, including marketing research and clinical trials management. Artificial intelligence has transformed pharmaceuticals, improving efficiency, accuracy, and innovation. This review highlights AI's role in drug development and personalized care, serving as a reference for professionals. The future promises a revolutionized field with AI-driven methodologies.

Nanotechnology in medicine: prospects for integration with telemedicine, digital technologies, and AI

The article examines the prospects of integrating nanotechnology with telemedicine, digital technologies, and artificial intelligence in modern medicine. It analyzes potential applications of nanomedicine in diagnostics, therapy, regenerative medicine, and the development of new drug formulations. Special attention is given to the role of nanosensors in remote patient monitoring, nanorobots in telesurgery, and nanocomputers in medical data processing. The advantages and challenges of implementing nanotechnology in clinical practice are discussed, as well as its potential in transforming healthcare, making it more personalized, efficient, and accessible.

GGAS2SN: Gated Graph and SmilesToSeq Network for Solubility Prediction.

Aqueous solubility is a critical physicochemical property of drug discovery. Solubility is a key issue in pharmaceutical development because it can limit a drug's absorption capacity. Accurate solubility prediction is crucial for pharmacological, environmental, and drug development studies. This research introduces a novel method for solubility prediction by combining gated graph neural networks (GGNNs) and graph attention neural networks (GATs) with Smiles2Seq encoding. Our methodology involves converting chemical compounds into graph structures with nodes representing atoms and edges indicating chemical bonds. These graphs are then processed by using a specialized graph neural network (GNN) architecture. Incorporating attention mechanisms into GNN allows for capturing subtle structural dependencies, fostering improved solubility predictions. Furthermore, we utilized the Smiles2Seq encoding technique to bridge the semantic gap between molecular structures and their textual representations. Smiles2Seq seamlessly converts chemical notations into numeric sequences, facilitating the efficient transfer of information into our model. We demonstrate the efficacy of our approach through comprehensive experiments on benchmark solubility data sets, showcasing superior predictive performance compared to traditional methods. Our model outperforms existing solubility prediction models and provides interpretable insights into the molecular features driving solubility behavior. This research signifies an important advancement in solubility prediction, offering potent tools for drug discovery, formulation development, and environmental assessments. The fusion of GGNN and Smiles2Seq encoding establishes a robust framework for accurately forecasting solubility across various chemical compounds, fostering innovation in various domains reliant on solubility data.

Gastrointestinal-inert prebiotic micro-composites improve the growth and community diversity of mucosal-associated bacteria.

The process of microencapsulation and the development of microparticle-based drug formulations have gained increased pharmaceutical interest, particularly for drug delivery and bacterial-encapsulation purposes for probiotic delivery. Existing studies have examined microcomposite (MC) responses to gastrointestinal (GI) conditions with the aim of controlling disintegration, and thus release, across the small and large bowel. However, the delivery of MCs which remain intact, without degrading, could act as bacterial growth scaffolds or materials providing a prebiotic support, conferring potentially beneficial GI health properties. This present study employs prilling as a method to produce a portfolio of MCs using a variety of biopolymers (alginate, chitosan, pectin and gellan gum) with a range of MC diameters and density compositions. Fluorescent probes are co-encapsulated within each MC to enable flow-cytometry directed release profile assessments following exposure to chemical simulated gastric and intestinal digestion conditions. We observe that MC size, gel-strength, density, and biopolymer material all influence response to gastric and intestinal conditions. Gellan gum (GG) MCs demonstrated complete resistance to disintegration throughout GI-simulation in the stomach and small intestine. Considering these MCs could reach the colon intact, we then examined how such MCs, doped with prebiotic growth supporting carboxymethyl cellulose (CMC) polymers, could impact microbial communities using a bioreactor model of the colonic microbiome. Following supplementation with GGCMC MCs, mucosal bacterial diversity (using 16 s rRNA sequencing and Shannon entropy and observed feature diversity metrics) and taxonomic composition changes were observed. Concentrations of short chain fatty acid (SCFA) metabolites were also found to be altered. This is the first study to comprehensivelyexamine how MC physicochemistry can be manipulated to tailor MCs to have the desired GI release performance and subsequently, how GI-resistant MCs could have influential microbial altering properties and be adopted in novel prebiotic strategies.

Opportunities of topical drug products in a changing dermatological landscape

Despite the prevalence and the impact on quality of life of dermatological indications, drug products to treat such conditions have rarely been blockbusters. The prevailing perception of a limited commercial potential of dermatological drug products has restricted innovation and encouraged a more conservative development approach. For example, the focus was on repurposing/reformulation of existing active pharmaceutical ingredients (APIs) specifically for the topical delivery route.However, the situation is quite different today catalyzed in part by the blockbuster success of Dupixent (dupilumab), the first monoclonal antibody treatment for atopic dermatitis which has been approved by the US Food and Drug Administration (US FDA) in 2017. Dupixent's success not only encouraged the development of other biologics but also inspired the (re-)development of new dermal drug products that can reap the many benefits of topical administration.We have also witnessed a shift toward outsourcing development efforts (and associated risks) towards small- to mid-size pharmaceutical companies which often require support of contract research and development/manufacturing organizations (CRO and CDMO). Such trends also emphasize the need of greater expertise in topical formulation design, as well as associated commercial and regulatory considerations.Today, we believe that topical drug products remain not only an essential but also commercially viable class of dermatological therapeutics. In this opinion article, we will address the challenges as well as opportunities of coherent development strategies in the current market environment, formulation innovations of topical drug products and technological advances to facilitate rational topical drug formulation development.

Assessing the Compatibility of Menatetrenone with Excipients: A Spectroscopic Approach and Implication in Drug Formulation Development.

An experiment was conducted to evaluate the compatibility of menatetrenone with selected pharmaceutical excipients. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess drug-excipient compatibility. The present research systematically investigates the FTIR spectrum of each chemical compound separately and their physical blends, analyzing for possible shifts, alterations or novel peak that may indicate chemical interactions. This study aims to utilize spectral data interpretation to detect potential compatibility problems that may occur while design and production of menatetrenone containing dosage forms ensuring their increased stability and effectiveness. The FTIR results demonstrated that all the pharmaceutical excipients were compatible with menatetrenone. In conclusion, the compatibility of pharmaceutical excipients with menatetrenone was successfully assessed using FTIR that will aid in future design of formulations containing menatetrenone as therapeutic moiety.

Improving the Solubility, Stability, and Bioavailability of Albendazole through Synthetic Salts.

Albendazole (ABZ) is a highly effective yet poorly water-soluble antiparasitic drug known to form salts (ABZ-FMA, ABZ-DTA, and ABZ-HCl) with fumaric acid (FMA), D-tartaric acid (DTA), and hydrochloric acid (HCl). This research utilized a range of analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), to validate and characterize the solid-state properties of these drug salts. This study also assessed the solubility and intrinsic dissolution rate (IDR) of these salts under different pH conditions compared to the active pharmaceutical ingredient (API) and conducted stability studies. Moreover, the in vivo pharmacokinetic performance of ABZ salt was evaluated. The results of this study reveal that the new solid form of ABZ is primarily associated with amino acid esters and benzimidazole groups, forming intermolecular interactions. All three ABZ salts significantly improved the solubility and dissolution rate of ABZ, with ABZ-HCl demonstrating the optimal performance. Importantly, the drug salt exhibited robust physical stability when exposed to adverse conditions, including strong light irradiation (4500 ± 500 lux), high humidity (92.5 ± 5% relative humidity), elevated temperatures (50 ± 2 °C), and accelerated test conditions (40 °C/75 ± 5% relative humidity). Lastly, the in vivo pharmacokinetic analysis demonstrated that ABZ salt led to a substantial increase in AUC(0-24) and Cmax compared to ABZ. This elevation in solubility in aqueous solvents signifies that ABZ salt exhibits characteristics that can enhance oral bioavailability and pharmacokinetics. These findings provide potential solutions for the development of more effective and innovative drug formulations.

Investigation of Stabilized Amorphous Solid Dispersions to Improve Oral Olaparib Absorption.

In this study, we investigated the formulation of stable solid dispersions to enhance the bioavailability of olaparib (OLA), a therapeutic agent for ovarian cancer and breast cancer characterized as a BCS class IV drug with low solubility and low permeability. Various polymers were screened based on solubility tests, and OLA-loaded solid dispersions were prepared using spray drying. The physicochemical properties of these dispersions were investigated via scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier Transform Infrared Spectroscopy (FT-IR). Subsequent dissolution tests, along with assessments of morphological and crystallinity changes in aqueous solutions, led to the selection of a hypromellose (HPMC)-based OLA solid dispersion as the optimal formulation. HPMC was effective at maintaining the supersaturation of OLA in aqueous solutions and exhibited a stable amorphous state without recrystallization. In an in vivo study, this HPMC-based OLA solid dispersion significantly enhanced bioavailability, increasing AUC0-24 by 4.19-fold and Cmax by more than 10.68-fold compared to OLA drug powder (crystalline OLA). Our results highlight the effectiveness of HPMC-based solid dispersions in enhancing the oral bioavailability of OLA and suggest that they could be an effective tool for the development of oral drug formulations.

Systematic Review on Major Antiviral Phytocompounds from Common Medicinal Plants against SARS-CoV-2.

Viral infections are rising around the globe and with evolving virus types and increasing varieties of viral invasions; the human body is developing antimicrobial resistance continuously. This is making the fight of mankind against viruses weak and unsecured. On the other hand, changing lifestyle, globalization and human activities adversely affecting the environment are opening up risks for new viral predominance on human race. In this context the world has witnessed the pandemic of the human Coronavirus disease (COVID-19) recently. The disease is caused by the Coronavirus namely Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2). Developing potential and effective vaccine is also time consuming and challenging. The huge resource of plants around us has rich source of potent antiviral compounds. Some of these molecules may serve as tremendously potent lead molecules whose slight structural modifications may give us highly bioactive antiviral derivatives of phytocompounds. Every geographical region is rich in unique plant biodiversity and hence every corner of the world with rich plant biodiversity can serve as abode for potential magical phytocompounds most of which have not been extensively explored for development of antiviral drug formulations against various viruses like the HIV, HPV etc., and the Coronavirus, also known as SARS-CoV-2 which causes the disease COVID-19. Several phytocompounds from various medicinal plants have already been screened using in silico tools and some of them have yielded promising results establishing themselves as potent lead molecules for development of drugs against the highly mutating SARS-CoV-2 virus and thus these phytocompounds may be beneficial in treating COVID-19 and help human to win the life threatening battle against the deadly virus. The best advantage is that these phytocompounds being derived from nature in most of the cases, come with minimum or no side effects compared to that of chemically synthesized conventional bioactive compounds and are indigenously available hence are the source of cost effective drug formulations with strong therapeutic potentials.

Quality by Design Approach for the Stability Indicating Method Development and Validation of Selpercatinib Drug Formulation by using RP-HPLC

In method development quality design approach is useful for method goal identification evaluation, method selection and risk assessment. Selpercatinib is a drug used in the treatment of certain types of cancer. The method development includes selecting appropriate chromatographic conditions such as the mobile phase composition, column, and selection wave length. The aim is to achieve optimum separation and quantification of selpercatinib in the dosage form. Optimizing chromatographic conditions by using design expert software. The mobile phase methanol and 0.1% Acetic acid are used. The mobile phase range is 80:20 v/v. The range of this mobile phase is 80:20 .0.7 mL/min found flow rate. The retention time of selpercatinib is 3.20 minutes. The assay was found to be 99.01% for selpercatinib. Optimization was performed. Factorial design performed, i.e., flow rate and percentages of methanol. Analysis of variance confirmed that method parameters. UV detection at 220 nm. The International Council of Harmonization (ICH) guidelines ensure the accurate, precise and reliable results to validate the parameters is an acceptable range. Stress studies reveal that drugs were degraded acidic conditions, alkaline conditions, neutral conditions, oxidative conditions, and photolytic conditions. Hence the proposed method was stability, indicating using quality by design (QbD) approach all the method parameters were better understood. This systematic approach ensures a thorough understanding of the assay, facilitates process optimization, and enables effective control strategies to reduce variability and enhance product quality.

Ibuprofen Formulations: Permeability and Biodegradability Comparison Depending on the Type of Formulation

This study assesses ibuprofen’s permeability to different formulations and their biodegradation. Hydrogel, organogel, Eucerin ointment, silicone ointment, and zinc ointment were investigated. The objective was to comprehensively evaluate the therapeutic efficacy and environmental implications of these formulations. Diverse formulations were examined through the utilisation of Franz diffusion chambers to evaluate the in vitro permeability of both ibuprofen and ibuprofenate sodium. Moreover, biodegradation studies of the obtained formulations were carried out with activated sludge. The activity of the inoculum was confirmed by using SDS as a reference compound. The experimental settings used (carbon content and inoculum volume) were selected based on the criteria set by the OECD guidelines. Relevant parameters pertaining to the biodegradation process were estimated, including biodegradation values (%B) at specific time points, half-lives of initial compounds and API-containing formulations, and degradation phases (lag phase I; degradation phase II, and plate phase III). For comparison purposes, biodegradation studies were also carried out for the initial IBU and IBUNa compounds under the same conditions. The environmental implications of these findings underscore the need for a balanced consideration of therapeutic efficacy and environmental sustainability in pharmaceutical formulation design. This study provides valuable insights for pharmaceutical researchers, environmental scientists, and regulatory bodies involved in the development and assessment of drug formulations. The proposed method of removing NSAIDs from aquatic ecosystems is a cheaper alternative to techniques such as reverse osmosis, oxidation, UV degradation, or photolysis, which have not found practical use owing to the generation of toxic sludge or high capital and operating costs.

Development of bedaquiline nanoemulsions intended for paediatric multidrug-resistant tuberculosis: excipient selection and preformulation studies.

Preformulation investigations into the development of drug formulations, encompassing considerations related to the structure of the drug, excipients, composition, and physical attributes are crucial. This phase is pivotal in ensuring the ultimate success of nanoemulsion development. The objective of this study was to evaluate and define the properties of bedaquiline (BDQ) and the necessary excipients for the formulation of self-emulsifying BDQ-loaded nanoemulsions. To determine the saturation solubility of BDQ in various oils, an in-house validated HPLC method was used. Fourier transform infrared spectroscopy was utilised to identify and evaluate the compatibility between BDQ and the selected excipients. The water titration method was used to construct phase diagrams to identify the type of structure that resulted following emulsification and to characterise the behaviour of mixtures along dilution paths. The solubility studies revealed that BDQ exhibited the highest solubility in olive oil, with a solubility of 3.45 ± 0.041 mg/ml. The design space led to the formation of emulsions categorised as Winsor products. Importantly, the FTIR data indicated the absence of any potential interactions between BDQ and the chosen excipients. The preformulation studies were successful and facilitated the selection of compatible and suitable excipients for the formulation of BDQ-loaded nanoemulsions.