Scientia Pharmaceutica

20 pages, 2329 KB

Open AccessArticle

Multivariate Robustness Modeling of Cannabidiol and Δ⁹-Tetrahydrocannabinol Quantification Using Two-Level Full Factorial Design

by Athip Maha, Thanapat Songsak, Surang Leelawat and Chaowalit Monton

Sci. Pharm. 2026, 94(2), 42; https://doi.org/10.3390/scipharm94020042 - 20 May 2026

Abstract

The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol [...] Read more.

The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol concentration (80–85% v/v), flow rate (0.8–1.2 mL/min), column temperature (23–27 °C), and detection wavelength (208–212 nm). Seven analytical responses for each compound were assessed, including peak area, retention time, resolution, asymmetry factor, number of theoretical plates, capacity factor, and peak area difference relative to the reference method. Statistical analysis demonstrated that both main effects and interaction effects significantly influenced the measured responses. Design space construction was performed based on predefined acceptance criteria to ensure method robustness: resolution > 1.5, asymmetry < 1.5, number of theoretical plates > 2000, capacity factor > 2, and peak area difference within −5% to 5%. Predictive performance of the developed models was verified by comparing predicted and experimental results. Good agreement was observed under most conditions, whereas deviation was noted for THC quantification at a detection wavelength of 212 nm. Furthermore, CBD and THC contents determined under three selected operating conditions within the established design space were statistically comparable to those obtained using the reference method, except for the condition employing 212 nm detection. The Analytical GREEnness Metric Approach (AGREE) assessment indicated moderate greenness performance of the analytical procedure. Overall, the multivariate two-level full factorial design proved to be an effective tool for robustness modeling of the HPLC method for simultaneous quantification of CBD and THC. Full article

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21 pages, 15430 KB

Open AccessReview

Active Pharmaceutical Ingredients in Medical Cannabis: Manufacturer Profiling, Standardization Challenges, and Technological Compatibility

by Liliia Vyshnevska, Maryana Yaromiy, Iryna Pestun, Kaloyan D. Georgiev, Iliya Zhelev Slavov and Oleh Koshovyi

Sci. Pharm. 2026, 94(2), 41; https://doi.org/10.3390/scipharm94020041 - 18 May 2026

Abstract

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of [...] Read more.

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of innovative dosage forms. This study analyses international practices among API manufacturers to identify technological parameters necessary to overcome domestic market barriers and support the implementation of advanced drug delivery systems. Content analysis was conducted on regulatory documentation, professional literature, and manufacturers’ technical specifications. Candidate evaluation followed predefined inclusion and exclusion criteria. The study assessed compliance with Good Manufacturing Practice (GMP) requirements, extraction and purification technologies, the extent of analytical characterization, and batch-to-batch reproducibility. Purposive sampling enabled a comparative analysis of various technological approaches. Marked heterogeneity was observed in API standardization and analytical control indicators among manufacturers. Possession of a GMP certificate was found necessary but may be insufficient to ensure the pharmaceutical equivalence of materials. Differences in extraction methods and purification levels may affect stability profiles, pharmaceutical development strategies, and risk management related to final product quality. The findings demonstrate that manufacturer selection is a critical decision point in pharmaceutical development, with substantiated supplier choice directly influencing dosage form development and regulatory compliance. Full article

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19 pages, 498 KB

Open AccessArticle

Synthesis and Biological Evaluation of Thiazolyl-Benzene/Camphor Sulfonamide Derivatives as Antibacterial, Antioxidant, and Antidiabetic Compounds

by Sreenivas Avula, Satish Koppireddi, Micky D. Tortorella and Cleopatra Neagoie

Sci. Pharm. 2026, 94(2), 40; https://doi.org/10.3390/scipharm94020040 - 14 May 2026

Abstract

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g [...] Read more.

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g and 5i displayed significant activity against most Gram-positive bacteria (MICs 4.68–18.75 µg/mL), while 4b and 5i were active against most Gram-negative bacteria with similar MIC ranges. In the DPPH assay, 4e, 4f, 4g and 4h exhibited slightly stronger radical-scavenging activity than ascorbic acid (IC₅₀ ≈ 3.5–3.8 µM vs. 4.14 µM); 5f emerged as the best dual carbohydrate-digesting enzyme inhibitor, and 5b and 5e demonstrated selectivity toward α-amylase. Full article

(This article belongs to the Special Issue Heterocyclic Chemistry in Drug Design 3.0)

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25 pages, 10660 KB

Open AccessArticle

Machine Learning Integration of In-Silico QSAR, Graph Neural Networks and Docking Reveal Natural Products Inhibitors Against Mycobacterium tuberculosis

by Sakthidhasan Periasamy, Rajesh Ramasamy, Rajasekar Chinnaiyan and Arun Sridhar

Sci. Pharm. 2026, 94(2), 39; https://doi.org/10.3390/scipharm94020039 - 14 May 2026

Abstract

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, exacerbated by the emergence of multidrug-resistant strains and limited efficacy of existing therapies. Given the involvement of multiple essential mycobacterial proteins, multitarget drug discovery represents a rational therapeutic strategy. [...] Read more.

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, exacerbated by the emergence of multidrug-resistant strains and limited efficacy of existing therapies. Given the involvement of multiple essential mycobacterial proteins, multitarget drug discovery represents a rational therapeutic strategy. Methods: In this study, an integrated in silico pipeline combining machine learning–based quantitative structure–activity relationship modeling, graph neural network–driven drug–target affinity prediction, molecular docking, molecular dynamics (MD) simulations, and pharmacokinetic–toxicity profiling was employed to identify potential antitubercular leads from natural products. Results: A curated library of over 0.69 million compounds from the COCONUT database was systematically screened against seven essential M. tuberculosis protein targets. Machine learning and heterogeneous graph neural network models effectively captured complex ligand–protein interaction patterns, enabling high-confidence multitarget prioritization. Structure-based docking and MM-GBSA analyses revealed favorable binding affinities, further supported by 100 ns Molecular Dynamics simulations demonstrating stable binding and conformational integrity. In silico ADMET and toxicity predictions identified pharmacokinetically balanced candidates, while density functional theory calculations corroborated favorable electronic properties. Conclusions: Notably, a myricetin-based flavonoid glycoside exhibited consistent multitarget binding and dynamic stability across all targets. Overall, this study underscores the potential of integrated artificial intelligence and structure-based approaches in accelerating natural product-based antitubercular drug discovery and supports further experimental validation of prioritized leads. Full article

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23 pages, 1695 KB

Open AccessReview

Experimental Design in Pharmaceutical Formulation Development: Achievements, Limitations and the Transition Toward Intelligent Optimization

by Ayşe Türkdoğan, Tarek Alloush and Burcu Demiralp

Sci. Pharm. 2026, 94(2), 38; https://doi.org/10.3390/scipharm94020038 - 13 May 2026

Abstract

Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a [...] Read more.

Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a more systematic framework for studying formulation variables, manufacturing parameters, and Critical Quality Attributes (CQAs). Approaches such as factorial designs, response-surface methodology, and mixture designs have therefore become central to modern pharmaceutical development because they improve experimental efficiency and support the definition of design space. However, as formulations become more nonlinear, high-dimensional, and multi-objective, these classical approaches may no longer be sufficient on their own. This review examines the evolution of experimental design in pharmaceutical research, from one-factor-at-a-time experimentation to structured DoE/QbD strategies, and then to emerging intelligent optimization methods. Its central objective is to clarify when conventional DoE/QbD remains appropriate and when it should be complemented by machine learning, Bayesian optimization, digital twins, and closed-loop experimental systems. The review first summarizes the foundations and strengths of classical experimental design; then, it discusses its practical limitations in complex formulation settings, and finally evaluates how data-driven and hybrid approaches can extend pharmaceutical development. Evidence from tablets, capsules, nanocarriers, transdermal patches, and biotherapeutic systems suggests that intelligent optimization can improve predictive performance and experimental efficiency when used alongside, rather than instead of, established pharmaceutical development principles. Full article

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31 pages, 4218 KB

Open AccessArticle

Design, Synthesis and Biological Activity of Regioisomeric 3,5-Disubstituted Isoxazoles and 5-(Hydroxy)Isoxazolines with Aryl and Either (Diterpenylfuran-2-Carbonyl) or (Methylfuran-2-Carbonyl) Moiety

by Maksim E. Mironov, Dmitry S. Baev, Mohammad S. Hamad, Sergey A. Borisov, Vyacheslav I. Krasnov, Tatyana V. Rybalova, Maksim P. Pitukhin, Irina V. Sorokina, Tatyana G. Tolstikova, Andrey G. Pokrovsky, Anastasia I. Poltanovich and Elvira E. Shults

Sci. Pharm. 2026, 94(2), 37; https://doi.org/10.3390/scipharm94020037 - 12 May 2026

Abstract

Alkyn-1,2-diones have gained great attention as useful building blocks in organic synthesis. Regioselective synthetic routes towards 3,5-disubstituted isoxazoles, containing the methylfuroyl or diterpenylfuroyl moiety at the C-3 or C-5 position from alkyne-1,2-diones 1, 2, 3, are reported. The reaction with [...] Read more.

Alkyn-1,2-diones have gained great attention as useful building blocks in organic synthesis. Regioselective synthetic routes towards 3,5-disubstituted isoxazoles, containing the methylfuroyl or diterpenylfuroyl moiety at the C-3 or C-5 position from alkyne-1,2-diones 1, 2, 3, are reported. The reaction with hydroxylamine hydrochloride 6 in ethanol afforded the 1,2-addition products: 5-aryl-3-(methylfuran-2-carbonyl)isoxazoles (yield 61–94%) or 16-(5-arylisoxazole-3-carbonyl)labdatrienes (yield 48–97%). The reaction of alkynediones 1–3 with 6 in THF in the presence of triethylamine led to 5-hydroxy-4,5-dihydroisoxazoles and subsequent dehydration afforded regioisomeric 3-aryl-5-(methylfuran-2-carbonyl)isoxazoles or 16-(3-arylisoxazole-5-carbonyl)labda-trienes (yield 65–98%). New heterocyclic compounds exhibited significant analgesic action in acetic acid writhing and hot-plate tests, and the activity was comparable to reference drugs diclofenac sodium and celecoxib. Isoxazoles, which possessed the most analgesic activity, reduced the concanavalin A-induced inflammation by 34–51%; the effect was comparable to the drug indomethacin. The results of in vitro biological assays (MTT test) revealed that isoxazoles were non-toxic against the normal epithelial VERO cells, and 16-(3-aryl-5-hydroxyisoxazoline-5-carbonyl)labdatrienes 20–24 exhibited selective cytotoxicity against the breast adenocarcinoma MCF 7 (GI₅₀ = 4.7–8.3 μM) and cervical cancer cells C33 A (GI₅₀ = 3.4–4.7 μM). Molecular docking analysis to determine the binding potential of new molecules to the active site of human COX-1 and COX-2 enzymes was conducted. Full article

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24 pages, 5125 KB

Open AccessArticle

Investigation of the Efficacy of Qin Pi Extract in Alleviating Dry Eye Disease in Murine Models and Its Association with Suppression of Lymphangiogenesis

by Feiyun Wang, Jing Hao, Mengjie Li, Yuying Zhu and Jiange Zhang

Sci. Pharm. 2026, 94(2), 36; https://doi.org/10.3390/scipharm94020036 - 5 May 2026

Abstract

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E [...] Read more.

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E alone, QP-E combined with Bing Pian (BP), and an ophthalmic formulation (QP-D) comprising both constituents in a preclinical model of dry eye disease (DED). DED was induced in mice via subcutaneous scopolamine administration alone, whereas a more robust dry eye phenotype was established in rats through combined treatment with scopolamine and environmental stressors. Ocular surface evaluation included measurement of tear secretion volume and corneal fluorescein staining scores. The results demonstrated that both QP-E monotherapy and the QP-E–BP combination significantly ameliorated key pathological features of DED, including tear film instability and corneal epithelial damage. QP-D—formulated with rationally optimized concentrations of QP-E and BP—significantly enhanced basal tear secretion and attenuated corneal epithelial injury in both murine and rat dry eye models. Mechanistic investigations revealed that QP-E treatment markedly inhibited VEGF-C secretion from classically activated (M1) macrophages, suppressed phosphorylation-dependent activation of the VEGF-C/VEGFR-3 signaling axis, and consequently impaired lymphatic endothelial cell migration and in vitro tube formation. These correlative findings indicate that QP-E may partially alleviate DED by suppressing lymphangiogenesis; however, direct causal evidence—such as genetic ablation of VEGF-C or pharmacological inhibition of VEGFR-3—was not established in the present study. Collectively, our data yield a testable mechanistic hypothesis and propose a novel therapeutic strategy targeting lymphatic remodeling for DED intervention. Full article

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9 pages, 322 KB

Open AccessCase Report

Personalized Dosage System as a Tool for Detecting Adverse Drug Reactions: Pharmaceutical Intervention in a Polymedicated Patient

by Adama Peña-Vera, Sandra Dévora-Gutiérrez, Chaxiraxi Morales Marrero, Isabel V. Figueiredo and Susana Abdala Kuri

Sci. Pharm. 2026, 94(2), 35; https://doi.org/10.3390/scipharm94020035 - 30 Apr 2026

Abstract

Adverse Drug Reactions (ADRs) represent a major public health concern due to their impact on patient safety. In Spain, the Spanish Agency of Medicines and Medical Devices, through the FEDRA database, coordinates the reporting of suspected ADRs under real-world conditions of use, contributing [...] Read more.

Adverse Drug Reactions (ADRs) represent a major public health concern due to their impact on patient safety. In Spain, the Spanish Agency of Medicines and Medical Devices, through the FEDRA database, coordinates the reporting of suspected ADRs under real-world conditions of use, contributing to the continuous updating of safety information. In this context, community pharmacist, through Professional Pharmaceutical Care Services, plays a key role in the early detection of ADRs and Drug-Related Problems (DRPs). This article describes the case of a 70-year-old polymedicated woman included in a Personalized Dosage System (PDS). Following the substitution of diazepam with clonazepam and an increase in the dose of semaglutide, the patient developed urinary incontinence, nausea and abdominal pain. Coordinated intervention between the community pharmacy and primary care enabled adjustment of the clonazepam dose, optimization of semaglutide administration and discontinuation of unnecessary naproxen use. These measures resulted in improved treatment tolerance and safety, as well as optimization of pharmacotherapy. Full article

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15 pages, 864 KB

Open AccessArticle

Leveraging ChatGPT for Vancomycin Therapeutic Drug Monitoring: Simulation Using Bayesian Estimation and Hyperparameter Optimization

by Akira Kageyama, Takahiko Aoyama, Rikuya Maehara, Dai Harada, Takashi Kawakubo and Yasuhiro Tsuji

Sci. Pharm. 2026, 94(2), 34; https://doi.org/10.3390/scipharm94020034 - 29 Apr 2026

Abstract

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the feasibility [...] Read more.

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the feasibility of using ChatGPT for vancomycin (VCM) TDM based on Bayesian estimation. A total of 1000 virtual patients were generated by Monte Carlo simulations using a population pharmacokinetic model of VCM. Bayesian-estimated pharmacokinetic parameters and predicted concentrations were input into ChatGPT, and dosage regimens were compared among the three conditions, using temperature as a hyperparameter (T = 0.1, 0.5, and 1.0). Reproducibility was evaluated using the mode percentage in repeated runs. The reproducibility of the ChatGPT output was higher at T = 0.1 than at T = 0.5 and T = 1.0. When ChatGPT simulated the mode-recommended regimen (T = 0.1), the target attainment rate of the area under the serum concentration (AUC) (400–600 mg·h/L) improved from 25.5% (pre-optimization AUC (fixed-dose regimen)) to 71.5% (post-optimization AUC (ChatGPT-guided regimen)). These findings demonstrate that ChatGPT-based TDM using Bayesian estimation can enhance dose optimization. Adjusting the hyperparameter temperature to 0.1 improved reproducibility, suggesting that a reliable ChatGPT-assisted TDM support system may be clinically useful. Full article

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23 pages, 6651 KB

Open AccessArticle

An Integrated In Vitro and In Silico Approach Demonstrates Promising Anticancer Potential of Novel Cyclopenta[d]pyrimidine Derivatives

by Valmik Sopan Aware, Shreya Rajesh Rao, Sanjay Pundalik Khairnar, Arati Prabhu, Hetal Abhay Shah and Sonal M. Manohar

Sci. Pharm. 2026, 94(2), 33; https://doi.org/10.3390/scipharm94020033 - 29 Apr 2026

Abstract

Background: Cancer is a leading cause of mortality worldwide. Discovery of small molecules as anticancer agents is an active area of research, as these molecules possess the remarkable ability to interact with specific targets within cancer cells. Objectives: In vitro anticancer activity of [...] Read more.

Background: Cancer is a leading cause of mortality worldwide. Discovery of small molecules as anticancer agents is an active area of research, as these molecules possess the remarkable ability to interact with specific targets within cancer cells. Objectives: In vitro anticancer activity of six hit derivatives from a series of 2-phenyl-substituted 4-amino–6, 7-dihydro-5H-cyclopenta[d]pyrimidines was tested against human cancer cell lines, viz., A549 (human lung cancer) and A431 (human skin cancer). Methods: Cytotoxicity was evaluated for six hits by the standard MTT assay. Further, their effect on clonogenic potential and cell cycle was tested using colony forming assay and flow cytometric analysis, respectively. Apoptosis-inducing potential was confirmed using Caspase-3/7 Glo assay and detection of cleaved caspase-3 by immunofluorescence. The effect on cell migration was tested using a wound healing assay. Target analysis, Molecular docking and ADMET simulations were performed to identify molecular targets, interactions and assess pharmacokinetic profiles. Results: Specific derivatives showed good to moderate cytotoxicity against A549 and A431 (with average IC50 in the range of ~30 µM), and these hits led to apoptosis and G1 arrest in these cell lines, respectively. Furthermore, identified hits inhibited cell migration in A549 cells. Computational consensus target analysis identified EGFR and CDK2 as high-confidence targets. Docking studies indicated favorable interactions and stability, whereas the ADMET analysis confirmed the drug-likeness and optimal pharmacokinetic and safety profiles of the small molecules. Conclusions: Our current study demonstrates the anticancer potential of novel pyrimidine derivatives. We envisage the use of these small molecules as promising anticancer agents, particularly in skin and non-small cell lung cancer. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Heterocyclic Compounds)

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16 pages, 3471 KB

Open AccessArticle

Analytical Method Optimization, Evaluation and Characterization of Ivermectin Solid Dispersion Formulations Using Hydrophilic Carriers

by Sajib Chandra Roy, Md. Jahid Hossain, Uttom Kumar, Sreedam Chandra Das, Fatema Moni, Deepankar Sutradhar, Faria Tasneem and A. S. M. Monjur Al Hossain

Sci. Pharm. 2026, 94(2), 32; https://doi.org/10.3390/scipharm94020032 - 22 Apr 2026

Abstract

Improving the dissolution and solubility of poorly water-soluble drugs remains a major challenge in drug development. Solid dispersion (SD) techniques offer an effective strategy by which to enhance the bioavailability of BCS Class II drugs such as ivermectin (IVM). This study aimed to [...] Read more.

Improving the dissolution and solubility of poorly water-soluble drugs remains a major challenge in drug development. Solid dispersion (SD) techniques offer an effective strategy by which to enhance the bioavailability of BCS Class II drugs such as ivermectin (IVM). This study aimed to develop and validate stability-indicating analytical methods for the quantification of IVM and to evaluate the performance of the formulated SDs. A novel RP-HPLC and a UV spectrophotometric method were developed and validated in accordance with ICH guidelines. IVM SDs were prepared via physical mixing (PM), solvent evaporation (SE), and melt fusion (MF) using Poloxamer 188, Kollicoat^® IR, and PEG 6000 at respective ratios of 1:1, 1:3, and 1:5. Dissolution studies showed a marked enhancement in drug release from SDs prepared by SE and MF methods compared with pure IVM. Among all formulations, the Poloxamer 188-based binary SD prepared by the SE method at a 1:5 ratio exhibited the highest dissolution (98.55% at 60 min), with release kinetics following anomalous (non-Fickian) transport (n = 0.681) according to the Korsmeyer–Peppas model. Solid-state characterization evidenced by FTIR, DSC, TGA, and SEM confirmed the transformation of IVM from its crystalline form to an amorphous state. Future studies will focus on the in vivo evaluation of the optimized IVM SD formulations. Full article

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20 pages, 2857 KB

Open AccessArticle

Development and Characterization of Melatonin-Loaded Glycerol–Gelatin-Based Vaginal Suppositories for Localized Delivery

by Regina Julieta Delgadillo Hernández, Gregorio Guadalupe Carbajal Arízaga, José Alfonso Cruz Ramos, Rodolfo Hernández Gutiérrez, José Armando Hernández Díaz, Ana Alejandra Arias García, Norma Morales-Hernández, José Nabor Haro-González, Zaira Yunuen García Carvajal and Moisés Martínez Velázquez

Sci. Pharm. 2026, 94(2), 31; https://doi.org/10.3390/scipharm94020031 - 17 Apr 2026

Abstract

This research aimed to develop glycerol–gelatin vaginal suppositories loaded with melatonin to enhance the localized effects of antineoplastic agents. The solubility of melatonin in different solvents was determined, and glycofurol, which is approved for pharmaceutical use, presented the highest solubilizing capacity. Furthermore, the [...] Read more.

This research aimed to develop glycerol–gelatin vaginal suppositories loaded with melatonin to enhance the localized effects of antineoplastic agents. The solubility of melatonin in different solvents was determined, and glycofurol, which is approved for pharmaceutical use, presented the highest solubilizing capacity. Furthermore, the cytotoxicity of melatonin incorporated into suppositories against HeLa cells was evaluated using MTT assays, individually and in combination with cisplatin. The results indicate that melatonin enhances the cytotoxic effects of cisplatin. The optimal formulation obtained from an experimental design was 33% gelatin, 1% PVA, 1% PEG 6000, 10% glycerol, 15% glycofurol, and 40% water. To ensure that the vaginal suppositories presented the necessary physical properties for optimal handling and application, tests were performed to determine weight uniformity, texture, surface features and disintegration time. Vaginal suppositories weighted around 1.43 g, showed Young’s modulus values of 7389.6 N/m² and hardness around 1100 g_f, and they disintegrated after 30 min at pH 4.2. Additionally, for in vitro melatonin release, FTIR and XRD tests confirmed the presence of melatonin in the formulation. It is concluded that the developed vaginal suppositories can be explored as potential vehicles for localized delivery of melatonin to the tumor site to enhance therapeutic outcomes. Full article

(This article belongs to the Topic Complementary Strategies in Drug Delivery: From Particle Engineering to System Optimization)

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17 pages, 2368 KB

Open AccessArticle

In Silico ADMET Profiling and Drug-Likeness Evaluation of Novel Thiopyrano[2,3-d]thiazole Derivatives as Potential Anticonvulsants

by Maryna Stasevych, Mykhailo Hoidyk, Viktor Zvarych, Andriy Karkhut, Svyatoslav Polovkovych and Roman Lesyk

Sci. Pharm. 2026, 94(2), 30; https://doi.org/10.3390/scipharm94020030 - 9 Apr 2026

Abstract

The development of novel antiepileptic agents requires early identification of pharmacokinetic limitations to mitigate risks at later stages. This study aimed to perform in silico profiling of a library containing 448 novel 2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-2-one derivatives to select lead [...] Read more.

The development of novel antiepileptic agents requires early identification of pharmacokinetic limitations to mitigate risks at later stages. This study aimed to perform in silico profiling of a library containing 448 novel 2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-2-one derivatives to select lead compounds with an optimal balance of safety and efficacy. The study was conducted using the ADMET-AI platform, based on a graph neural network, to predict physicochemical, pharmacokinetic, and toxicological properties. The methodology involved calculating drug-likeness descriptors for primary screening and a comparative statistical analysis of the top 20 selected structures against 16 approved antiepileptic drugs and four reference compounds. Based on drug-likeness descriptors and predicted ADMET (absorption, distribution, metabolism, excretion, toxicity) related parameters, 20 structures were prioritized for further analysis. Their predicted profiles suggested high intestinal absorption and blood–brain barrier (BBB) permeability, which may be relevant for central nervous system (CNS) directed agents. In comparison with the reference thiazolidinones, the prioritized compounds showed comparatively more favorable predicted mutagenicity and carcinogenicity profiles. Elevated predicted risks of hepatotoxicity and cardiotoxicity were observed for several structures, indicating the need for further structural optimization. The results suggest that the thiopyranothiazolidinone scaffold merits further anticonvulsant-oriented investigation at the stage of early compound prioritization. Experimental validation will be required to confirm the actual pharmacokinetic, toxicological, and anticonvulsant properties of the prioritized compounds. Full article

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33 pages, 2766 KB

Open AccessReview

Three Decades of Taxanes: Exploring the Next Frontier

by Rita I. L. Catarino, Maria Fernanda C. Leal, Adriana M. Pimenta, Maria Renata S. Souto and Francisco A. M. Silva

Sci. Pharm. 2026, 94(2), 29; https://doi.org/10.3390/scipharm94020029 - 8 Apr 2026

Abstract

Taxanes, such as paclitaxel and docetaxel, are microtubule-stabilizing agents widely used in oncology, either as monotherapy or in combination regimens. While highly effective, these first-generation taxanes face important limitations, including significant toxicity, reduced water solubility, and the emergence of multidrug resistance. To address [...] Read more.

Taxanes, such as paclitaxel and docetaxel, are microtubule-stabilizing agents widely used in oncology, either as monotherapy or in combination regimens. While highly effective, these first-generation taxanes face important limitations, including significant toxicity, reduced water solubility, and the emergence of multidrug resistance. To address these challenges, semi-synthetic taxoids have been developed, aiming to improve pharmacological profiles and overcome therapeutic barriers. Central to these efforts is the understanding of structure-activity relationships, which guides the rational design of taxane analogues with enhanced efficacy and safety. This review explores recent advances in taxoid development, highlights findings from clinical trials, and evaluates how these new agents compare with traditional taxanes in terms of therapeutic potential and tolerability. While novel delivery systems offer improved outcomes with existing drugs, the development of new taxane analogues remains a promising approach to address drug resistance, albeit with challenges related to toxicity, high costs, and historically low success rates in drug development. Furthermore, taxanes are already used in certain cardiovascular conditions and show emerging potential in neurodegenerative diseases, although current evidence remains largely limited to preclinical or early-phase clinical studies. These developments mark an important evolution in the field and offer new opportunities for future therapeutic strategies. Full article

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26 pages, 2726 KB

Open AccessReview

Orodispersible Tablets for Paediatric Use: A Systematic Review and Outlook for Future Research

by Samia Farhaj, Omar Hamid, Noman Ahmad, Barbara R. Conway and Muhammad Usman Ghori

Sci. Pharm. 2026, 94(2), 28; https://doi.org/10.3390/scipharm94020028 - 5 Apr 2026

Abstract

Children are often underserved by adult-oriented oral medicines, leading to off-label use and dosage-form manipulation that may compromise dosing accuracy. This review summarises recent advances in paediatric orodispersible tablets (ODTs), focusing on manufacturing technologies, superdisintegrants, taste masking, and in vitro disintegration testing. Following [...] Read more.

Children are often underserved by adult-oriented oral medicines, leading to off-label use and dosage-form manipulation that may compromise dosing accuracy. This review summarises recent advances in paediatric orodispersible tablets (ODTs), focusing on manufacturing technologies, superdisintegrants, taste masking, and in vitro disintegration testing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and a protocol registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (registration number INPLASY2025110022), we searched PubMed, EMBASE, MEDLINE, Scopus, and Google Scholar for experimental studies on paediatric-relevant ODT formulation and evaluation. Two reviewers screened studies and extracted data on manufacturing methods, excipients, disintegration/dissolution testing, and key outcomes. Risk of bias was assessed using a six-domain framework. Overall, 65 studies met the inclusion criteria for this review. Direct compression was the dominant method, with freeze-drying, sublimation, spray-drying, nanoparticle-in-tablet systems, and semi-solid extrusion/3D printing also reported. Crospovidone, croscarmellose sodium, and sodium starch glycolate were the most common superdisintegrants, while natural and co-processed disintegrants showed promise as cost-effective alternatives. Disintegration was usually assessed using pharmacopoeial methods, with some modified set-ups to better simulate oral conditions. Paediatric ODT development is advancing rapidly. Broader translation requires harmonised disintegration testing, age-stratified acceptability reporting, and GMP-ready workflows, alongside benchmarking of superdisintegrants and attention to dose flexibility, packaging, and affordability. Full article

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45 pages, 1270 KB

Open AccessReview

Kalanchoe daigremontiana from Ornamental to Pharmaceutical Applications

by Cecilia Guadalupe de Loza-García, Ana Belem Rubio-García, Salvador Hernández-Estrada, Luis Alfonso Hernández-Villaseñor, Luis Antonio Ramirez-Contreras, Jorge Manuel Silva-Jara, Jorge L. Mejía-Méndez, Zuamí Villagrán, Eugenio Sánchez-Arreola, Napoleón González-Silva and Luis Miguel Anaya-Esparza

Sci. Pharm. 2026, 94(2), 27; https://doi.org/10.3390/scipharm94020027 - 31 Mar 2026

Abstract

Kalanchoe daigremontiana, a succulent herbaceous plant in the Crassulaceae family from Madagascar, has gained global popularity as an ornamental and medicinal species. This review examines the traditional uses, phytochemical composition, biological properties, toxicological aspects, and regulatory challenges of K. daigremontiana. The [...] Read more.

Kalanchoe daigremontiana, a succulent herbaceous plant in the Crassulaceae family from Madagascar, has gained global popularity as an ornamental and medicinal species. This review examines the traditional uses, phytochemical composition, biological properties, toxicological aspects, and regulatory challenges of K. daigremontiana. The traditional medicinal uses of its leaves and roots include treating burns, rheumatic disorders, hypertension, diabetes, kidney pain, diarrhea, cough, fever, gastric issues, anxiety, inflammation, and cancer. Chemical compounds identified include phenolic acids, flavonoids, tannins, alkaloids, glycosides, saponins, sterols, terpenes, and fatty acids, with phenolic compounds and bufadienolides being predominant. In vitro studies of the crude extracts, bufadienolide-rich fractions, and isolated compounds have shown antioxidant, antibacterial, antifungal, antiviral, antiparasitic, anthelmintic, anti-inflammatory, anticoagulant, anti-aging, cytotoxic, antitumoral, and antiproliferative properties. In vivo studies have demonstrated hepatoprotective, skincare, and cardiac-glycoside-like effects. While crude extracts and bufadienolide-rich fractions have shown toxic effects in 2-week-old chicks, guinea pigs, and Artemia salina, no toxicity has been reported in goats, broiler chickens, laying hens, or human erythrocytes. Although K. daigremontiana-based products are commercially available as dietary supplements with various health claims, these lack scientific validation. Despite the potential pharmaceutical applications of K. daigremontiana, further research is needed to determine its effects, dosage, mechanisms, long-term safety, and side effects, with clinical studies essential to validate its therapeutic potential. Full article

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23 pages, 1785 KB

Open AccessArticle

Synthesis, Characterization, Antioxidant and Antimicrobial Potentials of Novel Organometallic Compounds Derived from Quercetin

by Orlando Maia Barboza, Luan Henrique Santos Barreto, Felipe dos Santos Mendes, Ivana Ferreira Simões, Luís Filipe Gomes Santos, Carlos Fernando da Silva Ferreira, Luís Guilherme dos Santos de Sant’Anna, Tainá Santos Lima, Kaique Souza Santos de Jesus, Saul Vislei Simões da Silva, Victor Pena Ribeiro, Silvia Lima Costa, Gustavo Souza dos Santos, Lourdes Cardoso de Souza Neta and Aníbal de Freitas Santos Júnior

Sci. Pharm. 2026, 94(2), 26; https://doi.org/10.3390/scipharm94020026 - 27 Mar 2026

Abstract

Quercetin, one of the most abundant flavonoids in nature, has attracted the attention of many researchers due to its chemical and biological properties. A series of metal–quercetin complexes (Cu²⁺, Co²⁺, Zn²⁺, Sn²⁺, Al³⁺, [...] Read more.

Quercetin, one of the most abundant flavonoids in nature, has attracted the attention of many researchers due to its chemical and biological properties. A series of metal–quercetin complexes (Cu²⁺, Co²⁺, Zn²⁺, Sn²⁺, Al³⁺, Cd²⁺ and Mg²⁺) were synthesized and systematically characterized by Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV–Vis) and nuclear magnetic resonance (NMR). These analyses confirmed that the complexes predominantly form through coordination with the 4-carbonyl group and adjacent phenolic hydroxyls. This induces measurable shifts in the ν(C=O), ν(O–H), and π→π* transition bands relative to free quercetin. The antioxidant capacity of the complexes was evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH^•) radical scavenging method, 2,2′-Azinobis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS^•)⁺ radical activity, and Ferric Reducing Antioxidant Power (FRAP) assay. Several complexes exhibited higher radical scavenging efficiency than quercetin, with inhibition percentages exceeding 80% in the DPPH^• and ABTS^•+ assays. Others showed reduced activity due to the masking of redox-active hydroxyl groups during metal coordination. FRAP results corroborated these trends, indicating metal-dependent modulation of reducing power. Antimicrobial evaluation revealed that selected complexes were more active than free quercetin, particularly against Staphylococcus aureus and Candida spp., with minimum inhibitory concentrations (MICs) ranging from 75–250 μg mL⁻¹. Overall, metal complexation significantly alters the electronic structure and biological behavior of quercetin, highlighting the potential of metal–flavonoid complexes as multifunctional antioxidants and antimicrobials. Full article

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15 pages, 1773 KB

Open AccessArticle

Blue Light-Based Method to Induce Oxidative Stress on Rabbit Corneal Epithelial (RCE) Cells: Development and Validation

by Valentina Paganini, Mariacristina Di Gangi, Patrizia Chetoni, Silvia Tampucci, Daniela Monti and Susi Burgalassi

Sci. Pharm. 2026, 94(1), 25; https://doi.org/10.3390/scipharm94010025 - 21 Mar 2026

Abstract

Daily exposure to blue light emitted by digital devices has raised concerns about oxidative stress-mediated damage to the ocular surface. Despite growing interest, validated in vitro models to study blue light-induced oxidative stress in corneal epithelial cells remain limited. A reproducible in vitro [...] Read more.

Daily exposure to blue light emitted by digital devices has raised concerns about oxidative stress-mediated damage to the ocular surface. Despite growing interest, validated in vitro models to study blue light-induced oxidative stress in corneal epithelial cells remain limited. A reproducible in vitro method was developed using rabbit corneal epithelial (RCE) cells exposed to blue LED light (405 nm). Irradiation parameters were optimized to induce oxidative stress without causing overt cytotoxicity. Cellular viability, intracellular ROS production, and mitochondrial oxidative stress were assessed. The model was validated using reference antioxidants (ascorbic acid and oleuropein), oleuropein formulated in a drug-in-cyclodextrin-in-liposome system (OLE-DCL), and two commercial ophthalmic formulations applied before or after irradiation. Blue light irradiation at 4.57 W/m² for 30 min significantly increased intracellular and mitochondrial ROS levels while preserving cell viability, indicating sublethal photo-oxidative stress. Ascorbic acid effectively suppressed ROS generation, whereas free oleuropein showed reduced efficacy, likely due to photosensitivity. OLE-DCL significantly enhanced antioxidant activity under irradiation. The model also discriminated between protective and restorative treatment strategies. This study establishes a validated in vitro blue light-induced oxidative stress model for corneal epithelial cells, suitable for screening antioxidant compounds, formulations, and application strategies relevant to ocular surface protection. Full article

(This article belongs to the Special Issue Innovative Perspectives in Ocular Drug Research)

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23 pages, 2049 KB

Open AccessReview

Cytotoxic Potential of Diterpenoids from the Genus Croton Against Breast Cancer Cell Lines: A Comprehensive Review

by José Jailson Lima Bezerra, Mateus Araújo da Luz, Aline Peres Ferreira, Joseilton Franco França, Tatiana Porto Santos, Anderson Angel Vieira Pinheiro and Maria da Conceição de Menezes Torres

Sci. Pharm. 2026, 94(1), 24; https://doi.org/10.3390/scipharm94010024 - 21 Mar 2026

Abstract

Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. [...] Read more.

Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. In this context, considering the importance of evaluating less aggressive and more efficient therapeutic alternatives to aid in the treatment of breast cancer, the present study critically discusses the cytotoxic effects of diterpenoids isolated from Croton species (Euphorbiaceae). The articles were retrieved from different databases, from the first report published in 2005 to October 2025. A total of 115 diterpenoids were isolated from 15 Croton species and investigated against different breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-468). These compounds mainly belong to the kaurane group (40%), followed by clerodane (14%), tigliane (12%), and abietane (10%). Of this total, only 25 compounds showed promising results (IC₅₀ = < 10 µM). The mechanisms of action of the compounds crokokaugenoid A, kongensin A, kongensin D, ent-16β,17α-dihydroxykaurane, and lauicyclone A have been reported. These compounds likely act by inducing apoptosis, autophagy, cell cycle arrest, inhibition of cell migration and invasion, and DNA fragmentation in breast cancer cell lines. To date, no randomized clinical trials have been conducted using Croton diterpenoids for the treatment of breast cancer. Therefore, further studies on the modulation of the immune response by these natural products are essential to better understand their immunotherapeutic activity in the tumor microenvironment during breast cancer progression. Full article

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