Pharmaceutical Industry Research Articles

Quantitative systems toxicology modeling in pharmaceutical research and development: An industry-wide survey and selected case study examples.

Quantitative systems toxicology (QST) models are increasingly being applied for predicting and understanding toxicity liabilities in pharmaceutical research and development. A European Federation of Pharmaceutical Industries and Associations (EFPIA)-wide survey was completed by 15 companies. The results provide insights into the current use of QST models across the industry. 73% of responding companies with more than 10,000 employees utilize QST models. The most applied QST models are for liver, cardiac electrophysiology, and bone marrow/hematology. Responders indicated particular interest in QST models for the central nervous system (CNS), kidney, lung, and skin. QST models are used to support decisions in both preclinical and clinical stages of pharmaceutical development. The survey suggests high demand for QST models and resource limitations were indicated as a common obstacle to broader use and impact. Increased investment in QST resources and training may accelerate application and impact. Case studies of QST model use in decision-making within EFPIA companies are also discussed. This article aims to (i) share industry experience and learnings from applying QST models to inform decision-making in drug discovery and development programs, and (ii) share approaches taken during QST model development and validation and compare these with recommendations for modeling best practices and frameworks proposed in the literature. Discussion of QST-specific applications in relation to these modeling frameworks is relevant in the context of the recently proposed International Council for Harmonization (ICH) M15 guideline on general principles for Model-Informed Drug Development (MIDD).

Green strategies for the valorization of industrial medicinal residues of Serenoa repens small (saw palmetto) as source of bioactive compounds

Serenoa repens is a medicinal plant well-known for its therapeutic potential in treating various urological disorders and prevention of prostatic cancer. However, the extraction process in the pharmaceutical industry leads to the generation of plant residues, typically discarded, wasting valuable resources. In this study, we aimed to explore a series of green extraction strategies to effectively valorize the residues of Serenoa repens fruits. Initially, we employed supercritical CO2 (1.2% yield on dry biomass) on the discarded biomass to identify and quantify residual fatty acids and polyprenols (1.6% of the extract dry weight), a class of unsaturated isoprenoid alcohols with promising biomedical applications. Subsequently, subcritical water extraction was utilized on the exhausted biomass to extract polar compounds. An increase in the extraction yield was observed with the rise in processing temperature up to 180 °C (yields were found higher than 26%). Phenolic compounds and carbohydrate macromolecules profiles were affected by the increased hydrolytic conditions. Polar extracts exhibited robust bioactivities, demonstrating significant antioxidant activity and antimicrobial efficacy against Gram-positive and Gram-negative bacteria strains. Extracts obtained at 180 °C demonstrated the highest efficacy. Furthermore, in vitro assessment of mannans-rich fraction provided a new perspective of potential applications in the cosmeceuticals field. Results underscore the potential of the sustainable extraction biorefinery for the residue of this medicinal plant and demonstrate that, harnessing these bioactive compounds, new sustainable and eco-friendly approaches for its complete utilization can be offered, thereby promoting near-zero waste practices and contributing to a more sustainable future.

Extraction of bioactive components from date palm waste, various extraction processes and their applications: A review

Dates are vital sources of nutrients and bioactive components which are widely consumed throughout the world. Agro-industrial waste, such as date palm waste, has been recognized as a potential candidate of bioactive chemicals and essential oils for utilization in food, medicine, and cosmetics. Date fruit and seed are well-known for their nutritional worth, which includes high sugar, vitamins, and mineral content that includes potassium and magnesium. Presence of phenolic compounds diverges the attention of researchers towards efficient extraction processes. Various traditional e.g., soxhlet, maceration, infusion, and digesting and advanced extraction techniques, i.e., pressurised fluid extraction (PFE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and supercritical CO2 extraction (SC-CO2) have been discussed briefly to extract bioactive components for instance flavonoids, tocopherols, tannins, carotenoids, tocotrienols and hydroxybenzoic acid from date palm fruit, seed, and leaves. The findings reveal that the higher total phenolic content in a shorter time can be obtained by combining ultrasonic with PLE or SFE extraction techniques. These bioactive components can be used in the food and pharmaceutical industries for pre-treatment of certain ailments. Moreover, the natural bioactive components with potential therapeutic benefits, such as non-starch polysaccharides and selenium. The purpose of this study is to highlight the advances achieved in understanding bioactive components e.g., phenolic compounds, flavonoids, tannins hydroxycinnamic, hydroxybenzoic and bio-oil of date palm fruits, including their synthesis, probable functions, and health advantages, to find prospective uses for date-derived materials in the cosmetics, pharmaceutical and food sector.

The state of individual participant data sharing for the highest-revenue medicines.

Amid growing emphasis from pharmaceutical companies, advocacy groups, and regulatory bodies for sharing of individual participant data, recent audits reveal limited sharing, particularly for high-revenue medicines. Therefore, this study aimed to assess the individual participant data-sharing eligibility of clinical trials supporting the Food and Drug Administration approval of the top 30 highest-revenue medicines for 2021. A cross-sectional analysis was conducted on 316 clinical trials supporting approval of the top 30 revenue-generating medicines of 2021. The study assessed whether these trials were eligible for individual participant data sharing, defined as being publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. Information was gathered from various sources including ClinicalTrials.gov, the European Union Clinical Trials Register, and PubMed. Key factors such as the trial phase, completion dates, and the nature of the data-sharing process were also examined. Of the 316 trials, 201 (64%) were confirmed eligible for sharing, meaning they were either publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. A total of 102 (32%) were confirmed ineligible, and for 13 (4%), the sponsor indicated that a full research proposal would be required to determine eligibility. The analysis also revealed a higher rate of individual participant data sharing among companies that utilized independent platforms, such as Vivli, for managing their individual participant data-sharing process. Trials not marked as completed had significantly lower eligibility for individual participant data sharing. This study highlights that a substantial portion of trials for top revenue-generating medicines are eligible for individual participant data sharing. However, challenges persist, particularly for trials that are marked as ongoing and for trials where the sharing processes are managed internally by pharmaceutical companies. Data-sharing rates could be improved by adopting open-access individual participant data-sharing models or using independent platforms. Standardizing policies to facilitate immediate individual participant data availability for approved medicines is necessary.

Advancing Analytical Excellence: A Comprehensive Exploration of ICH Q14 in the Lifecycle of Analytical Procedure Development and Optimization

This research article addresses the complexities of analytical process development and optimization in line with the principles set out in the Commission's Effectiveness of the Requirements for Medicinal Products for Human Use (ICH) Q14 guidelines. Focusing on the pharmaceutical and chemical industry, this article describes the early stages of development in terms of sustainable lifestyles. The first study explores the important role of analytical procedures in ensuring product quality and regulatory compliance, introduces ICH Q14 and explains its scope and objectives. The fundamental principles of audit development are reviewed in depth, including risk assessment, design, and the interaction between Audit Objectives (ATP) and Methodology. Operational Development Region (MODR). Concepts such as Design of Operations (DoE) and Quality by Design (QbD) are under scrutiny for their development and optimization. Real-life case studies demonstrate the application of Q14 principles and demonstrate successful examples of effective methods and continuous improvement in drug screening, drug purity testing and environmental analysis. Looking ahead, this article explores how new technologies, potentially innovative regulations and international cooperation will shape the development landscape. Challenges such as the complexity of new compounds and the need for sustainable practices are addressed and the need for business professionals to be flexible and innovative is emphasized. In summary, this research article can serve as a general guide for professionals in the pharmaceutical and chemical industry, providing insight into the content, eight owners, and use of development analysis. Using the principles defined in ICH Q14, community auditors can investigate the changing landscape and make further progress on quality assurance.

The Impact of Macroeconomic Factors on Stock Valuation

The widely accepted notion that capital markets are significantly influenced by macroeconomic factors underscores the importance of examining how these factors directly and indirectly affect stock valuations. Stock prices are inherently volatile, subject to the whims of the market, yet they are expected to converge with the intrinsic value of the shares they represent. Uncovering this fair value is essential for strategic investment decisions. This review article aims to provide an in-depth analysis of the impact of macroeconomic variables on the financial performance of specific companies, using macroeconomic data to elucidate the shifts in the fair value of their shares. By focusing on Baiyunshan, a leading pharmaceutical company in China, the article illustrates the tangible effects of macroeconomic factors on stock valuation. It offers a comprehensive exploration of various evaluation models, providing investors with a robust framework to assess the intrinsic value of publicly traded pharmaceutical companies. This study not only bridges the gap in current understanding but also equips investors with the necessary tools to navigate the complexities of the capital market with greater confidence and precision.

The Influence of Aloe Vera Biocoagulant and Mixing Time in Reducing Biological Oxygen Demand, Chemical Oxygen Demand and Total Suspended Solids Levels

Aloe vera is a plant with complex composition of carbohydrates, sugars, and mucilage, enabling it to bind particles in water and serve as a coagulant in the coagulation-flocculation process. This study aims to assess the impact of varying doses and rapid stirring times on the reduction of biochemical oxygen demand (BOD), chemical oxygen demand (COD), and total suspended solids (TSS) levels in liquid waste from pharmaceutical companies. The research involves two factors: (1) aloe vera concentration at three levels (20 mL/L, 40 mL/L, and 60 mL/L); (2) fast mixing time at three levels (20 minutes, 40 minutes, and 60 minutes), with each treatment repeated thrice. Levels of BOD, COD and TSS were measured post-treatment using a jar test tool. The results of the analysis showed that the optimal efficacy of the aloe vera coagulant occurred at a concentration of 40 mL/L for 40 minutes. At this optimal condition, the effectiveness of the aloe vera coagulant in reducing BOD, COD and TSS levels was 72.3%, 78.5%, and 65.3%, respectively. This indicates that the aloe vera coagulant can be effectively utilized in the treatment of pharmaceutical industrial wastewater to reduce BOD, COD and TSS levels

Review article on self emulsifying system

The solubility challenges faced by the pharmaceutical industry, particularly with orally administered drugs, are indeed significant. Low aqueous solubility often leads to poor dissolution and subsequently, low bioavailability, which can result in inconsistent drug effects among patients. Various methods have been explored to address this issue, including salt formation, solid dispersion, and complex formation.Among these approaches, Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising solution for enhancing the solubility of lipophilic drugs. SEDDS consist of isotropic mixtures of hydrophilic solvents, co-solvents, and surfactants. They possess the unique ability to form fine oil-in-water micro emulsions upon mild agitation and dilution in aqueous media, such as gastrointestinal fluids.The advancement in SEDDS technology encompasses improvements in composition, evaluation methods, development of different dosage forms, and techniques for converting liquid SEDDS into solid forms. These advancements not only enhance solubility but also offer versatility in administration routes and dosage forms, thereby expanding the potential applications of SEDDS in pharmaceutical formulations.This comprehensive review provides valuable insights into the latest developments in SEDDS, offering a detailed account of its composition, evaluation parameters, diverse dosage forms, and innovative techniques for solidification. Moreover, it highlights the diverse applications of SEDDS across various therapeutic areas, underscoring its growing significance in modern pharmaceutical research and development.

Advancements of Biomacromolecular Hydrogel Applications in Food Nutrition and Health.

Hydrogels exhibit remarkable degradability, biocompatibility and functionality, which position them as highly promising materials for applications within the food and pharmaceutical industries. Although many relevant studies on hydrogels have been reported in the chemical industry, materials, and other fields, there have been few reviews on their potential applications in food nutrition and human health. This study aims to address this gap by reviewing the functional properties of hydrogels and assessing their value in terms of food nutrition and human health. The use of hydrogels in preserving bioactive ingredients, food packaging and food distribution is delved into specifically in this review. Hydrogels can serve as cutting-edge materials for food packaging and delivery, ensuring the preservation of nutritional activity within food products, facilitating targeted delivery of bioactive compounds and regulating the digestion and absorption processes in the human body, thereby promoting human health. Moreover, hydrogels find applications in in vitro cell and tissue culture, human tissue repair, as well as chronic disease prevention and treatment. These broad applications have attracted great attention in the fields of human food nutrition and health. Ultimately, this paper serves as a valuable reference for further utilization and exploration of hydrogels in these respective fields.

Could I become a physician in the pharmaceutical industry? - practical insights from a 12-year veteran in pharma

Could I become a physician in the pharmaceutical industry? - practical insights from a 12-year veteran in pharma

EVALUATION OF STUDENTS' TRAINING LEVEL IN THE ELECTIVE DISCIPLINE "QUALITY SYSTEMS IN PHARMACY"

The pharmaceutical industry is rapidly developing and implementing new innovative approaches and legal regulation of the quality management system of medicinal products, which includes a set of methods, processes and resources that are necessary for quality management. Therefore, the study by students of the specialty 226 "Pharmacy, industrial pharmacy" of the elective discipline "Quality systems in pharmacy" is an important area of professional training of a qualified specialist who will master the methodology of quality management, normative-legislative and organizational-economic aspects of quality control of medicinal products at pharmaceutical enterprises. Training of domestic students in the field of drug technology is an important direction of pharmaceutical education today. The main tasks of studying the elective discipline "Quality Systems in Pharmacy" are: formation of students of higher education in general knowledge about the quality indicators of medicinal products according to the stage of their life cycle by fulfilling the requirements of proper pharmaceutical practices and developing documentation in accordance with their requirements; formation of practical skills; raising the level of general and scientific development of students of higher education, forming their outlook and perspective as modern qualified specialists in the field of pharmacy. The purpose of the work was to study the assessment of the level of training of domestic students in the elective discipline "Quality Systems in Pharmacy". Materials and methods. We used an empirical research method (questionnaire). Questionnaire was a key research method, as it allows to get answers from the student audience regarding the organization of the educational process. A survey was conducted to assess the level of preparation of domestic students of the 5th year of the Faculty of Pharmacy who completed the study of the selective discipline "Quality Systems in Pharmacy". 50 full-time students and 2 distance learning students took part in the survey. Out of all the respondents, only one studies on budget forms of education. Research results. According to the curriculum, the elective discipline "Quality Systems in Pharmacy" at the Faculty of Pharmacy of IFNMU is studied in the V course in the IX semester, at the stage when students have already acquired basic knowledge of pharmaceutical disciplines. The discipline is chosen by already formed specialists who possess a large stock of theoretical knowledge and practical skills and are motivated to study a new subject, so it remains for the teacher to systematize information for the proper conduct of the discipline study course. 3 ECTS credits are provided for the study of the discipline in the curriculum. The discipline includes 20 hours of lectures, 30 hours of practical classes, 40 hours of independent student work and ends with a module. Lecture and practical material taught at the level of modern scientific and practical data with the aim of forming students' program results. We conducted an analysis of problems in the organization of the educational process for students of the Faculty of Pharmacy of the Ivano-Frankivsk National Medical University during full-time education. The success of implementing the selective discipline "Quality Systems in Pharmacy" and ensuring a high level of training depends primarily on the quality of the work of scientific and pedagogical workers.

Green Chemistry in Pharmaceutical Synthesis: Sustainable Strategies for Drug Production

The world is shifting from traditional synthetic or chemical technologies towards greener methods due to increasing concerns about maintaining a clean and sustainable environment. The development of eco-friendly products through processes that support environmental sustainability is referred to as a "green approach." In the pharmaceutical industry, there is growing attention to green synthesis of chemicals and materials, both in research and applied science, because green chemistry eliminates harmful processes and materials while promoting innovation in drug and therapeutic agent development. Green chemistry encompasses chemical reactions that minimize environmental impact and reduce toxicity. This field is rapidly evolving within pharmaceutical synthesis, focusing on the creation of sustainable medicines. This review explores the principles and practical applications of this innovative strategy within the pharmaceutical sector. By using environmentally friendly chemical processes, green chemistry reduces hazardous materials and pollution. Its aim is to mitigate the environmental footprint of drug production without compromising the quality and effectiveness of medicines. The approach also emphasizes the use of renewable and sustainable resources, such as shifting from petrochemical-based to bio-based feedstocks, allowing pharmaceutical companies to reduce their greenhouse gas emissions

The Resilience of Supply Chain: The Case of Vietnamese Pharmaceutical Companies

The Resilience of Supply Chain: The Case of Vietnamese Pharmaceutical Companies

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.

Nanoparticulate Herbal Formulation for the Management of Fungal Infection

Abstract: Fungal infections have been more common during the past few years as a result of an increase in the population of immunocompromised people, including those with cancer, HIV/AIDS, and organ transplant recipients. It has been reported that fungal infection is brought on by different pathogens. The main focus of this review is the use of nanosized plant components to stop fungal infections for the pharmaceutical industry and research projects. According to research about 40 million people have fungal infections. Echinocandins, griseofulvin, azoles, allylamines, and flucytosine are only a few antifungal medications used in clinical settings to treat fungal infections. Skin infections caused by fungi are among the most prevalent dermatological issues of today. Fungal infections at the skin's surface or under the skin's surface may harm the skin, keratinous tissues, and mucous membranes. Therefore, there is a high need for producing an antifungal agent that may act selectively on new targets while having minor side effects and can belong to a variety of structural classes. Natural goods offer limitless prospects for innovative medicine development due to their typically unrivaled chemical variety, whether in the form of pure phyto-compounds or standardized plant extracts. Plants have been an excellent source of medicine since the beginning of time. When compared to synthetically produced medications, phytochemicals from various plant species have been versicolor as a more potent source of therapy. Novel cell targets and antifungal chemicals, as well as new methods for the delivery of drugs based on nanotechnology, are all currently being studied.

Improving the bioconversion of phytosterols to 9α-hydroxy-4-androstene-3,17-dione by disruption of acyltransferase SucT and TmaT associated with the mycobacterial cell wall synthesis.

The bioconversion of low value-added phytosterols into high value-added 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) in Mycolicibacterium neoaurum is a representative step in the steroid pharmaceutical industry. However, the complex mycobacterial cell walls with extremely low permeability and flowability greatly decrease the overall conversion efficiency. Herein, we preliminarily identified two key acyltransferases encoded by Mn_TmaT and Mn_SucT required for the proper synthesis of cell wall in mycobacteria and achieved a significant increase in cell permeability by disrupting them without affecting the cell wall structural stability. At length, the destruction of Mn_TmaT and Mn_SucT alone increased the conversion rate of 9-OHAD from 45.3% (6.67 ± 0.39g/L) to 62.4% (9.19 ± 0.58g/L) and 67.9% (10.02 ± 0.62g/L) while the continuous destruction of Mn_TmaT and Mn_SucT did not further improve the conversion efficiency of 9-OHAD. Notably, it was investigated that the continuous destruction of Mn_TmaT and Mn_SucT led to alterations in both the covalent and non-covalent binding layers of the cell wall, resulting in excessive changes in cell morphology and structure, which ultimately decreased 9-OHAD production. Therefore, this study deciphered a pivotal biosynthetic path of cell wall and provided an efficient and feasible construction strategy of 9-OHAD synthesis in mycobacteria.

Coating Tablets, Compositions, Recent Advancement and Current Status: A Comprehensive Review

Conventional Tablets are solid oral dosage forms that contain an active pharmaceutical ingredient (API) along with excipients. These tablets are typically prepared through direct compression, wet granulation, or dry granulation. They are designed to disintegrate and release the API in a controlled or immediate manner, depending on the formulation. Tablet coating is a vital process in pharmaceutical technology, designed to improve the therapeutic efficacy, patient compliance, and stability of oral dosage forms. This comprehensive review explores the key aspects of tablet coating, including the types, compositions, and recent advancements. Coating materials such as polymers, plasticizers, and pigments are discussed in detail, along with their roles in controlling drug release, masking taste, and enhancing aesthetic appeal. The recent advancements focus on innovative coating techniques like film coatings, enteric coatings, and the application of nanotechnology to improve precision and functionality. Additionally, the current status of tablet coating is analyzed in terms of regulatory compliance and industry trends. The review highlights the future potential of personalized coatings, smart coatings, and environmentally friendly approaches, showcasing the evolving landscape of tablet coating technologies/pans in modern pharmaceutical manufacturing and development. Keywords: Table coating; dosage form; enteric; coating pans; formulation; advancement; polymers

Artificial Intelligence (AI) Applications in Drug Discovery and Drug Delivery: Revolutionizing Personalized Medicine

Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI’s applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI’s transformative impact on the pharmaceutical industry and its broader implications for healthcare.

Factors affecting the performance of government R&D support programs in pharmaceutical enterprises

Purpose The government support for research and development (R&D) initiatives in the pharmaceutical sector has been declining. The purpose of this study is to analyze factors influencing the efficacy of government R&D support programs directed at pharmaceutical enterprises in South Korea, aiming to provide valuable insights for policymakers responsible for resource allocation in the pharmaceutical industry. Design/methodology/approach The study uses data from 490 R&D projects conducted by 106 pharmaceutical enterprises between 2018 and 2020, sourced from the National Technical Information Service and Drug Approval Research and Technology repositories. The data were analyzed using negative binomial regression analysis operated by the Statistical Package for the Social Sciences. Findings Applied research, cooperative research and the number of doctoral researchers positively impact both the quantitative and qualitative performance of the papers. The number of doctoral researchers, government research funds and the ratio of private investment to total R&D investment positively impacted the quantitative and qualitative performance of patents. However, enterprise age negatively affected patent performance. Notably, sales were significantly associated with patent qualitative performance but not with patent quantitative performance. Originality/value While previous studies have primarily focused on specific types of government R&D support or individual sectors, this study provides a broader perspective by incorporating a variety of variables, to examine the overall performance of government R&D programs in the pharmaceutical sector. This paper addresses the growing concern over declining government support and offers insights that were not fully explored in prior studies. By doing so, this research highlights the importance of understanding how diverse factors collectively influence the effectiveness of government R&D support, providing new directions for innovation and excellence in the pharmaceutical industry.

AQbD-guided stability indicating HPLC method for azelnidipine and chlorthalidone fixed-dose combination tablet: a green approach

This study developed a stability-indicating RP-HPLC method for quantifying azelnidipine and chlorthalidone in fixed-dose formulations using Analytical Quality by Design (AQbD) principles. A Plackett-Burman design was used for factor screening, followed by risk assessment and optimization using a central composite design to evaluate the effects of the organic phase percentage, flow rate, and modifier concentration. Acetonitrile percentage was identified as the most critical factor. The optimized method employed a Reliant™ C18 Waters column with a mobile phase of 0.1% formic acid and acetonitrile (62:38% v/v), with chlorthalidone and azelnidipine eluting at 4.1 and 13.7 minutes, respectively. Validation showed the method's robustness, accuracy, and precision. Forced degradation studies confirmed its reliability for tablet formulation analysis, and an Analytical Greenness score of 0.55 highlighted its environmental sustainability. This method is efficient, simple, and well-suited for routine quality control in the pharmaceutical industry.