Pharmaceutical Science: New Insights and Developments Vol. 9

Methodological Advances in the Study of Drug-Drug Interactions

2025-11-11T10:50:11+00:00

Drug-drug interactions (DDIs) represent a critical pharmacokinetic parameter that significantly influences the efficacy and safety of therapeutic agents. While the majority of DDI studies employ in vitro methodologies, in vivo and in silico approaches are also applied. This book chapter provides a comprehensive summary of the various methods utilised to study drug-drug interactions. We thoroughly explain and discuss nine prominent in vitro techniques: UV-VIS absorption spectral analysis, conductometric analysis, Ardon’s method, Job’s continuous variation method, Differential Scanning Calorimetry (DSC), FTIR spectroscopic investigation, and Thin Layer Chromatography (TLC)—all demonstrated through the detection of interactions between two model drugs (DRUG A and DRUG B). Additionally, we cover fluorescence spectroscopy, exemplified by its use in examining drug-protein interactions and high-performance liquid chromatography (HPLC), as applied to detect the interaction between drugs and their excipients. Furthermore, we outline fundamental in vivo methods, which typically involve the use of young, healthy animals of varying body weights. Finally, we explore three key in silico methods: Quantitative Structure–Activity Relationship (QSAR) Models, Molecular Docking and Molecular Dynamics (MD) Simulations, and Physiologically Based Pharmacokinetic (PBPK) Modelling and AI and ML methods. Overall, this chapter offers an in-depth exploration of DDI methodologies and serves as an accessible and foundational guide for researchers wanting to conduct DDI studies.

Formulation and Design of Metformin and Glibenclamide in Controlled-Release Osmotic Capsules

2025-11-11T10:58:21+00:00

Background: Diabetes mellitus (DM) is a disorder of carbohydrate metabolism characterised by chronic hyperglycemia, although lipid and protein metabolism are also affected. Underlying its pathophysiology is a deficit in insulin secretion or action, or there may be a simultaneous deficit in both insulin secretion and activity. Diabetes represents a global health challenge. In 2021, it was estimated that 536.6 million people suffered from this disease. Today, a wide range of drugs is available for the treatment of Type 2 Diabetes Mellitus. In 2022, in Mexico, the most cost-effective intervention for Type 2 Diabetes was a combined oral treatment of metformin and glibenclamide, with a total cost of USD 951.75, an effectiveness rate of 42.30%, and an effectiveness coefficient of 2.25. Osmotic systems offer clear advantages over conventional pharmaceutical forms, as they allow for the maintenance of constant plasma concentrations over long periods.

Aims: This study aims to target the improvement of the treatment of people suffering from Diabetes. Rather than using multiple doses and dosage forms for effective treatment, the author provides a robust solution in the form of a combination of drugs as an osmotic capsule, which has a controlled release pattern and aims at treating the disease effectively. This study also presents, for the first time, a compatibility study using a non-destructive methodology with a Raman spectrometer, which can be considered as the article’s novelty.

Methodology: A compatibility drug-excipient with Raman spectroscopy study at 50°C for four weeks was conducted. A 32 experimental design was successfully developed to obtain controlled-release osmotic capsules containing metformin/Glibenclamide. Pharmaceutical Technology Laboratory, College of Pharmacy, Universidad Autonoma del Estado de Morelos. 2013-2015. Compatibility study between Metformin and Glibenclamide with 15 excipients using Raman spectrofotometer during 4 weeks at 50C, then manual encapsulation of the 9 formulations and coating with cellulose acetate in acetone and finally release study in two steps: 2.5 hours in gastric medium and ten hours in enteric medium for a total of 12.5 hrs of release study.

Results: Capsules free of excipient incompatibilities, with a constant release rate over 12.5 hours, independent of pH and stirring speed. These controlled-release osmotic capsules were sealed and coated with a cellulose acetate membrane, with a weight gain of 3% and a release hole of 635 μm. The best formulation exhibited lag times of 2.09 hours for metformin and 0.18 hours for glibenclamide. The 1:1 Mannitol-Sorbitol mixture in this study showed a reduction in osmotic potential, with Mannitol exhibiting lower osmotic potential and Sorbitol providing the highest osmotic potential. The most important findings indicate that the release rate for both drugs remained linear for 12.5 hours, with the lag time being close to zero. The lag time in the systems was better when the highest level of osmotic agent (sorbitol) and the highest amount of the osmotic agent (100 mg) were present in the osmotic system.

Conclusion: For the first time presented a compatibility study was presented using a nondestructive methodology with a Raman spectrometer. The capsules presented constant release for 12.5 hours; the best lag time was 2.09 hours for metformin and 0.18 hours for Glibenclamide. the mixture 1:1 sorbitol– mannitol presented a reduction in osmotic potential. The limited release rate of glibenclamide may be attributed to its solubility constraints. The combination of a high amount of sorbitol as the osmotic agent, along with the use of non-disintegrating capsules, effectively reduced the system's lag time. The manuscript compares the pharmacological agents used by diabetes patients, and they have to take multiple doses for the efficacy of the treatment with an osmotic system, improving treatment adherence through controlled release, easier and more effective with a lower number of administrations.

In silico Evaluation of Bioactive Molecules from Scoparia dulcis L. as Potential Inhibitors of SARS-CoV-2 Main Protease (\(M^{pro}\))

2025-11-11T11:02:03+00:00

Background: The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 coronavirus, remains a global threat despite lifting the health emergency. This pandemic has affected all areas of human life, with the most devastating consequences affecting health and the economy. Scientists from all continents have been mobilised to develop vaccines and medicines for prevention and cure. In Burkina Faso, traditional healers proposed using Scoparia dulcis L., a medicinal plant, to manage COVID-19. Scoparia dulcis L. is a medicinal herb widely used in Africa, America, and Asia. More than 160 compounds with therapeutic potential have been found in S. dulcis.

Aim: This study aims to identify bioactive molecules from Scoparia dulcis L. that could potentially inhibit the SARS-CoV-2 main protease (M^pro) through in silico methods.

Methods: In silico screening offers a quick drug-likeness evaluation of Scoparia dulcis L.- isolated biomolecules toward SARS-CoV-2 targets, such as M^pro protease. A review of the literature retrieved 35 biomolecules isolated from Scoparia dulcis. Compounds isolated from polar extracts (water and alcohol) were used in this study. Autodock Tools were used to optimise the selected ligands. All molecular docking experiments were performed using AutoDock Vina® software. The potential interactions of these biomolecules with the amino acid residues of the SARS-CoV-2 M^pro protease were visualised. Affinities and probable oral route delivery were assessed using reference molecules such as remdesivir and nelfinavir.

Findings: The screening allowed the retention of 20 hit molecules, which had a better affinity for the target than the reference molecules remdesivir and nelfinavir, and analysis of the results identified height lead molecules with a significant interaction with the M^pro protease and being druggable. There are six flavonoids: cirsimarin, cynaroside, hydroxy-tetramethoxyflavone, gossypetin, luteolin, vitexin, one diterpene, glutinol, and one glycoside, eugenyl-glucoside. These molecules interact with methionine 6, and tyrosine 126 of SARS-CoV-2 M^pro. These two amino acids are essential for the dimerisation of M^pro protease. Inhibitory action on M^pro protease can be expected from these biomolecules.

Conclusion: Scoparia dulcis L. could help manage COVID-19 because it contains biomolecules that can inactivate SARS-CoV-2 M^pro. These findings provide a basis for further in vitro and in vivo validation of Scoparia dulcis phytocompounds as potential anti-COVID-19 agents.

Limnophila heterophylla (Scrophulariaceae): A Review of Chemical and Pharmacological Aspects

2025-11-11T11:10:18+00:00

Limnophila (family: Scrophulariaceae) originates from a Latin word that means pond-loving, indicating its existence in aquatic environments. This is an aquatic, or nearly aquatic, perennial herb found as a submersed, emergent, and amphibious stem plant. Limnophila plants are extensively used in the indigenous system of medicine and are found to be useful and effective. This study offers a review of the chemistry and pharmacology of Limnophila heterophylla (Roxb.) Benth., recognised as one of the most significant plant species in traditional medicine and established as a source of flavonoids, terpenoids, etc. The isolated phytochemicals, as well as different extracts, exhibited some kind of biological activities such as antimicrobial, anti-inflammatory, and wound healing. Exhaustive research regarding the isolation of more phytochemicals and pharmacology studies on this medicinal plant is still necessary so as to explore the plant regarding its medicinal importance. This review encourages contemporary researchers to undertake further investigations, ultimately facilitating the development of effective drugs derived from Limnophila heterophylla in the near future.

Pharmacological Evaluation of Tamarindus indica Leaf Extract: Analgesic, Anti-inflammatory, and CNS Depressant Effects

2026-01-12T11:20:05+00:00

Background: Tamarindus indica leaves have been traditionally used to manage pain, inflammation, and disorders of the nervous system. Different parts of plants—including leaves, fruit pulp, bark, and seeds—are traditionally used to treat fever, gastrointestinal disorders, inflammation, pain, and various infections. Scientific evidence supporting these uses is limited, prompting an evaluation of their pharmacological activities in experimental models.

Aim: The present study aimed to evaluate the pharmacological effects of Tamarindus indica leaf extract, specifically its analgesic, anti-inflammatory, and central nervous system (CNS) depressant activities, in order to assess its potential therapeutic applications.

Methods: Fresh leaves of T. indica were collected from the campus of the University of Rajshahi, Bangladesh. An aqueous extract of T. indica leaves was administered to mice at doses of 50 mg/kg and 100 mg/kg. Analgesic activity was assessed using the acetic acid–induced writhing test. Anti-inflammatory effects were measured through carrageenan-induced paw oedema. Central nervous system (CNS) depressant activity was examined using the Open Field and Hole Cross tests to determine changes in locomotor and exploratory behaviours.

Results: The extract produced significant, dose-dependent analgesic effects, with 100 mg/kg showing 77.94% inhibition of writhing, comparable to the standard drug (83.33%). Anti-inflammatory activity also increased with dose and time, with notable suppression of paw oedema at later phases of inflammation. In CNS activity tests, both doses—particularly 100 mg/kg—significantly reduced movement and exploratory behaviours, indicating strong CNS depressant action.

Conclusion: T. indica leaf extract exhibits potent analgesic, anti-inflammatory, and CNS depressant properties in mice. These effects may involve modulation of inflammatory pathways and central neurotransmitter systems such as GABA. The results support traditional uses of the plant and highlight its potential for future development of natural therapeutic agents. Further studies are needed to identify active compounds and clarify their mechanisms of action.

Synthesis, In silico, and Pharmacokinetic Drug Likeness of Some Schiff Bases as Hybrid Antibacterial and Antifungal Agents

2026-01-12T11:24:51+00:00

Background: Schiff bases, which may be synthesised from sulfonamide and aldehydes, have a broad range of biological effects in clinical medicine, are also referred to as anticancer and antiviral medicines. Sulfonamides and their derivatives are frequently reported for their antibacterial, antiviral, antifungal, anticancer, and anti-inflammatory properties.

Objective: The aim of the study was to synthesise new derivatives of sulfonamide compounds containing azo and Schiff base fragments and confirm the structures by 1H-NMR and FT-IR spectroscopy, as well as to investigate the antibacterial activities against medically important Gram (+) and Gram (-) bacterial strains.

Methods: Novel sulfonamide derivatives S1, S2, S3, A1, A2, and A3 were synthesised and tested with Staphylococcus aureus and Pseudomonas aeruginosa as well as against Candida albicans fungi. Studies on antimicrobial agents were carried out using the agar diffusion method. Molecular docking was used to study the theoretical binding of the compounds with some selected proteins. Docking studies were carried out using the program MOE (2015.10).

Results: The results of antimicrobial evaluation revealed that especially compounds of Schiff bases (S1, S2, and S3) exhibited good activity against all microorganisms of bacteria and fungi as compared with A1, A2, and A3. Against Candida albicans, it was found that compounds S1 and S3 gave the best activity, 21 and 20 mm, respectively. Antibacterial activity showed that compound A2 gave the best activity (34 mm at 1000 µg/mL) against Staphylococcus aureus. Other compounds S1, S2, S3, A1, and A3 gave very good activities against the same bacteria, 29, 13, 29, 28, and 28 mm, respectively, at the same concentration. Antibacterial activity against Pseudomonas aeruginosa revealed that the compound S1 gave the best inhibition zone (25 mm) at 1000 µg/mL, whereas compounds S2 and S3 showed good potent activity (15 and 20 mm, respectively). In Silico studies showed that free binding energy (S) of the compounds against S. aureus using protein 1JIJ were -7.15 to -8.60 kcal/mol, whereas free binding energy (S) using 5V5Z fungi protein gave the values -7.10 to -8.22 kcal/mol.

Conclusion: Schiff base derivatives exhibited superior antimicrobial activity compared with azo derivatives. A clear correlation was observed between the activity of the compounds and their molecular docking through the high negative values of free binding energy. This investigation revealed these compounds with binding energies that were on par with those of typical medications. Additionally, these compounds were shown to be powerful antibacterial agents bioactivity score and bioavailability radar analysis.

Dermatological Applications of Punica granatum: Phytochemistry and Therapeutic Potential in Skin Disorders

2026-01-12T11:29:02+00:00

Pomegranate (Punica granatum) is a popular fruit known for its rich nutritional value and diverse bioactive compounds. The fruit has many potential health benefits, and it has been evaluated in clinical trials for different diseases. There are limited studies investigating the comprehensive use of pomegranate in cosmetic and dermatological applications. This chapter presents a comprehensive review of the dermatological applications and therapeutic potential of Punica granatum, with a focus on its phytochemistry and mechanisms of action. The increasing use of botanical extracts in skincare and cosmetic formulations underscores the relevance of Punica granatum, a plant native to Iran. A structured literature search was conducted across various databases, including PubMed, ScienceDirect, Springer, and Google Scholar, to evaluate evidence from preclinical and clinical studies. Key findings indicate that pomegranate extracts and their bioactive compounds—particularly punicalagin, ellagic acid, and anthocyanins—exhibit significant antioxidant, anti-inflammatory, antimicrobial, and wound-healing properties. Specific dermatological benefits explored include the promotion of wound repair, inhibition of acne pathogenesis, protection against UV-induced photoaging, skin brightening, and management of inflammatory skin conditions such as atopic dermatitis. This review consolidates current scientific research to highlight the promising role of Punica granatum as a multifunctional agent in the treatment and prevention of skin disorders, supporting its continued integration into dermatological and cosmetic products.

Metered-Dose Inhalers: Contemporary Technologies, Industrial Development, Regulatory Considerations, and Emerging Trends

2026-01-12T11:31:07+00:00

Background and objective: Metered-dose inhalers (MDIs) remain fundamental to the management of asthma and chronic obstructive pulmonary disease (COPD) due to their portability, dosing accuracy, patient convenience, and cost-effectiveness. Despite advances in inhalation therapy encompassing formulation science, device engineering, and regulatory frameworks, MDIs continue to occupy a central role in clinical practice and pharmaceutical development.

Objectives: This chapter provides a comprehensive and critical overview of contemporary MDI technologies, including conventional pressurised MDIs, breath-actuated devices, and non-pressurised soft mist inhalers (SMIs). Key aspects addressed include operating principles, formulation and propellant considerations, device design, aerosol performance, and dose delivery characteristics. The chapter further evaluates recent technological advancements, clinical benefits, and persistent challenges, including patient adherence, environmental sustainability, and dose reproducibility. Industrial and regulatory perspectives influencing inhalation product development and commercialisation are also discussed.

Methodology: This chapter is based on a structured critical review of current scientific, technical, and industrial literature related to MDI development and performance. Peer-reviewed research articles, review papers, pharmacopeial standards, and regulatory guidance documents were systematically analysed to capture advances in formulation science, device technology, regulatory expectations, and sustainability initiatives. Authoritative guidance from regulatory agencies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the International Council for Harmonisation (ICH) was examined to contextualise development and compliance requirements. Particular emphasis was placed on device engineering, aerosol generation and characterisation, formulation device interactions, and the application of quality-by-design (QbD) principles across product development, manufacturing, and lifecycle management.

Conclusions: MDIs remain indispensable in the long-term treatment of asthma and COPD; however, their continued clinical relevance depends on effectively addressing challenges related to patient misuse, adherence, and the environmental impact of hydrofluoroalkane (HFA) propellants. Future progress in MDI technology will require an integrated, multidisciplinary approach that combines advances in formulation science, environmentally sustainable propellant alternatives, and user-centred device design. From a regulatory and quality standpoint, critical performance attributes such as aerodynamic particle size distribution, emitted dose uniformity, extractables and leachables assessment, and robust in vitro-in vivo correlations will remain essential for ensuring product safety and therapeutic efficacy. Alignment with evolving regulatory expectations, supported by risk-based design strategies and QbD-driven development, will be pivotal in advancing next-generation MDIs that are clinically effective, patient-friendly, and environmentally responsible. Emerging trends and future research directions are highlighted to provide a forward-looking framework for researchers, clinicians, and industry stakeholders in inhalation drug delivery.

Revealing The Gut-brain Connection: The Effects of Microbiota Extend Beyond Digestion

2026-01-12T11:33:28+00:00

The gut microbiome is a dynamic internal ecosystem that plays a crucial role in shaping our overall health. A balanced gut microbiome aids in digestion, nutrient absorption, immune function, mental clarity, and emotional regulation, and protects against diseases such as diabetes, neurodegenerative disorders, and autoimmune conditions. Comprising bacteria, viruses, fungi, and other microorganisms, this vast ecosystem is essential but often overlooked in its impact on health. It transforms dietary components into important neurotransmitters and antioxidants, including serotonin and indole-3-propionic acid (IPA). However, factors like poor diet, excessive hygiene, stress, and antibiotic use can disrupt this delicate balance by decreasing microbial diversity and impairing function. The gut microbiota is linked not only to digestive diseases but also to mental health conditions. This chapter emphasises the influence of stress, probiotics, circadian rhythms, diet, and environmental exposures on the gut microbiota’s interaction with brain function via the gut-brain axis—a bidirectional communication system. It explores how gut microbes affect the nervous system through neurotransmitters, the endocrine system, immune mechanisms, and microbial metabolites. Additionally, it discusses how alterations in gut microbiota may be involved in psychiatric disorders such as major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD).