Pakistan journal of pharmaceutical sciencesMuhammad Sajid Nawaz, Muhammad Zaman, Huma Hameed, Waqar Siddique, Ahmad Salawi, Yosif Almoshari, Jawaher Abdullah Alamoudi
BACKGROUND: Multiparticulate Drug Delivery (MDD) system are particularly considered as well suited systems for controlling oral preparations that have low risk of dose-dumping. OBJECTIVES: The current research work was aimed to prepare Fexofenadine HCl immediate release (IR) and Paracetamol sustained release (SR) pellets in a single dosage unit for the treatment of Allergic Rhinitis. Extrusion-spheronization was used to fabricate pellets. METHODS: The formulations were analyzed for several parameters, including micromeritic studies, Friability, Weight variation test, Swelling, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), in-vitro release and stability studies. RESULTS: The results showed that the formulated pellets have an excellent flowability (23.01° to 25.23°), bulk density falls in the range of 1.23 g cm -3 to 1.42 g cm -3 , tapped density ranges 1.43 g/cm 3 1.58 g/cm 3 , carr's compressibility index lie between 10.31 % to 15.17 %, Hausner's ratio ranges 1.11 to 1.18 which concluded pellets had good flow properties. Friability was less than 1%; the T6 formulation showed the maximum swelling of 99.28%. No interaction between excipient and drug was found. T6 showed a drug release of 99.08% in 24 hours. CONCLUSION: The research effectively demonstrated that preparing a single-unit dosage form of paracetamol and fexofenadine is a safe, simple and promising technique for SR of Paracetamol, thereby increasing patient compliance by reducing the dosage frequency.
Pakistan journal of pharmaceutical sciencesOrcun Can
BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.
Basic & clinical pharmacology & toxicologyAbraham García-López, Andrea Guzmán-de Antonio, Tania S Rubio-Lepe, Elena Diago-Sempere, Juan Raffo-Nogueira, Pedro Arias, Belén Ferrer-Martínez, Sonia Rodrigu…
VKORC1 genetic variants are major determinants of interindividual variability in vitamin K antagonist (VKA) dose requirements and are incorporated into several pharmacogenetic dosing guidelines. The promoter variant rs9923231 is considered the clinically relevant marker for genotype-guided VKA dosing. However, the intronic variant rs9934438 is sometimes used as a surrogate marker because it is assumed to be in strong linkage disequilibrium with rs9923231. We aimed to assess whether rs9934438 can reliably substitute rs9923231 in clinical practice. We conducted a retrospective, single-centre study including 939 patients who underwent pharmacogenetic testing. Both variants were genotyped using a TaqMan OpenArray custom panel. Concordance between rs9934438 and rs9923231 was evaluated, and the diagnostic performance of rs9934438 for predicting clinically relevant rs9923231 diplotypes was assessed. Although concordance was high overall, rs9934438 misclassified two patients who, according to rs9923231, required a reduced VKA dose, resulting in potential false-negative classifications. These findings indicate that, while rs9934438 provides informative results in most cases, it may fail to identify some patients requiring dose adjustment. Our results highlight the clinical implications of relying on surrogate markers in pharmacogenetic-guided VKA therapy and support the preferential use of rs9923231 to ensure accurate individualized dosing and optimize treatment safety.
Drug development researchShuyu Jia, Jieman Lin, Janjun Wu, Hao Xu, Qingwei Zeng, Meipin Liu, Jiayi Shen
BRAF is a cytoplasmic serine-threonine protein kinase that plays a critical role in the MAPK signaling pathway. BRAF is the only member of the RAF family activated by mutation in human cancers. Many classes of B-Raf small molecule inhibitors have been identified. In this review, we will highlight typical BRAF inhibitors developed during these decades and provide a reference for the exploration of more potential BRAF inhibitors in the future.
Natural products, including isolated compounds, complex extracts, traditional medicinal preparations and marine, microbial, fungal and animal-derived materials, remain important sources of therapeutic agents and pharmacological discovery. However, variation in biological source materials, preparation methods, chemical composition and experimental design may compromise reproducibility and interpretation. This guideline presents the requirements of Basic & Clinical Pharmacology & Toxicology for studies involving natural products and their semisynthetic or biotransformed derivatives. It provides recommendations for documenting scientific and ethnopharmacological rationale, taxonomy, authentication, provenance, sustainable and lawful sourcing, extraction, chemical characterisation, dosing, bioactivity, safety and data accessibility. Particular emphasis is placed on studying the preparation actually administered, using pharmacologically relevant concentrations and doses, controlling vehicle effects and assay interference and aligning mechanistic and therapeutic claims with the supporting evidence. Complex mixtures do not necessarily need to be reduced to a single active constituent; however, their composition must be adequately characterised, and claims concerning individual constituents, additivity, synergy or antagonism require experimental substantiation. Computational, network and systems-pharmacology analyses should be transparent and reproducible, with experimental validation of central predictions. These recommendations apply equivalent standards to natural products and other interventions while recognising the additional information required to define complex biological materials and improve overall translational relevance.
ChemMedChemJosé Arion da Silva Moura, Matheus Vinicius Guimarães de Melo, Diane Regis Santos do Nascimento, Thaynara Paula Warren Bezerra, Mathieu Métifiot, Patricia Reco…
The therapy to treat the Human Immunodeficiency virus (HIV) and decrease the viral load has been a challenge since its discovery due to its ability to mutate, escape from drug therapies, and immunologic system. Consequently, the development of new therapies, especially potential molecules that focus on specific viral mechanisms to block viral replication, became a critical challenge in recent decades. The Reverse Transcriptase (RT) is an RNA- and DNA-dependent DNA polymerase enzyme that is responsible for transcribing viral RNA into double-stranded DNA. Non-nucleoside RT Inhibitors perform important role in HIV therapy, and they are responsible for inhibiting RT by blocking its allosteric site, which shows physico-chemical properties such as high hydrophobicity and key amino acid-to-hydrogen bond interactions. For this reason, designing new molecules with innovative heterocycles compatible with these characteristics can provide new potential inhibitors. For example, pentacyclic heterocycles like thiazole and its derivatives like thiazolidinedione, which have physico-chemical properties that can interact with the allosteric site of RT, can be a new perspective in designing new Non-nucleoside RT Inhibitors. This work reviews the scientific literature concerning these compounds and can help the design of new antiviral therapeutics.
The pharmacogenomics journalOchuko M Orherhe, Omolabake F Ayodele, Jeremiah O Omojuyigbe, Ayodapo O Jegede, Olumide A Alade, Kikelomo Oladimeji, Oluwatimilehin S Ogunde, Promise U Okereke…
This study assessed the knowledge, attitude, and perception of pharmacogenomics among healthcare workers in Southwest Nigeria. A structured, questionnaire-based survey was administered to 229 healthcare workers in Southwestern Nigeria using a stratified sampling approach. Descriptive and inferential statistics using the Kruskal-Wallis or Chi-Square/Fisher's Exact test were performed with SPSS v. 29 at a 5% significance level. Good general knowledge was displayed by half of the participants (123, 53.7%), but specific knowledge declined significantly. The majority (200, 87.3%) expressed interest in receiving further education, with healthcare practitioners with <5 years' experience expressing higher optimism for getting involved in pharmacogenetic testing (p = 0.003) and expressing greater ability to identify sources of information on pharmacogenomics (p = 0.02). This suggests a significant gap between current educational provisions and the requisite understanding needed to implement pharmacogenomics effectively in the Nigerian healthcare system.
BMJ openStefanie Lip, Pieter Theo Pepler, Alex McConnachie, Leslie J Sheffield, Sam Mostafa, Linsay McCallum, Neil Hawkins, Olivia Wu, Louise Bennett, Iain Frater, Kat…
INTRODUCTION: Pharmacogenomic (PGx) panel testing may reduce adverse drug reactions (ADRs), treatment failures and downstream healthcare use by aligning prescribing with germline genetic variation. The PREPARE trial reported an approximately 30% reduction in clinically relevant ADRs using a pre-emptive multigene panel, but its open-label design, patient-reported endpoint and subsequent methodological critiques limit its use for National Health Service (NHS) decision-making. Whether panel-based PGx delivers benefit in acute NHS secondary care, where prescribing is time-critical, patients are older and multimorbid and outcomes can be linkage-adjudicated, remains unknown. METHODS AND ANALYSIS: PHOENIX is a pragmatic, pilot, parallel-group, individually randomised controlled trial with blinded outcome adjudication, in NHS Greater Glasgow and Clyde (NHSGGC) hospitals and NHS Golden Jubilee National Hospital. Adults newly prescribed an eligible PGx-relevant index drug are identified through a data-driven screening system integrating electronic prescribing, community prescribing linkage and record review and randomised 1:1 to PGx-guided care or standard care with delayed PGx testing. In the intervention arm, buccal-swab DNA is genotyped (Clinical Laboratory Improvement Amendments/College of American Pathologist (CLIA/CAP)-accredited laboratory) and a Clinical Pharmacogenetics Implementation Consortium (CPIC)/Dutch Pharmacogenetics Working Group (DPWG)-based report returned within approximately 10 days; results are research-use-only. The trial aims to recruit 2000-4000 participants constrained by a fixed operational end-date (30 September 2026). The primary outcome is index-drug-related ADR or treatment failure within 3 months, adjudicated using Common Terminology Criteria for Adverse Events (CTCAE) V.6 and validated causality tools, with deterministic linkage via the West of Scotland Safe Haven. Secondary outcomes include ADR severity, hospitalisations, mortality, actionable prescribing uptake, biomarker levels, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and healthcare utilisation. The primary analysis is intention-to-treat logistic regression adjusted for stratification factors; a within-trial cost-utility analysis estimates cost per quality-adjusted life year (QALY). ETHICS AND DISSEMINATION: Approved by Scotland A Research Ethics Committee (24/SS/0064; IRAS 344412; NHS R&I INGN24MG113). Co-sponsors are NHSGGC and the University of Glasgow. Findings will be disseminated via peer-reviewed publication, conferences, patient and public involvement and engagement-co-produced lay summaries and the trial website. TRIAL REGISTRATION NUMBER: NCT06907784.
MedicineMasi A Almalki, Saleh A Almarshad, Ghadeer A Joudah, Nouf M Alourfi, Saad M Wali
Pharmacology teaching in pharmacy education remains largely lecture-driven, which can encourage surface learning and limit student engagement. Student-led presentations offer an active-learning approach that may combine conceptual learning with communication, teamwork, and professional-skill development. This study explores pharmacy students' perceptions of how student-led pharmacology presentations influenced their understanding, communication confidence, collaboration, and perceived academic and professional preparedness. A qualitative descriptive cross-sectional study was conducted among 90 second-year Doctor of Pharmacy students at Umm Al-Qura University, Makkah, Saudi Arabia, in Spring 2025. Following 6-minute group presentations, participants completed an anonymous open-ended questionnaire. Responses were examined using Braun and Clarke's 6-phase reflexive thematic analysis. An audit trail, peer debriefing, comparison across questionnaire domains, and iterative review of themes against the complete dataset supported analytic trustworthiness. Five interconnected themes were generated: Deepened Understanding and Active Learning Engagement; Growth in Communication Confidence; Collaboration and Team Synergy; Professional and Academic Preparedness; and Endorsement and Recommendations for Integration. Students' accounts associated the activity with active knowledge construction, practice in scientific communication, shared responsibility, and transferable academic and professional skills. Time pressure, unequal participation, cognitive load, and presentation anxiety were also identified as qualifying conditions. Students perceived student-led presentations as a feasible, low-cost strategy that supported engagement, pharmacological understanding, communication, and teamwork. Because the findings derive from a single-institution, post-activity self-report dataset, they indicate pedagogical promise rather than causal effectiveness. Longitudinal and mixed-methods studies should assess objective learning, retention, transfer, and professional outcomes.
The present study explores the potential of sorafenib (SOR) and atorvastatin (ATST) to induce a ferroptosis and apoptosis-based hybrid cell death mechanism. The synergistic ATST + SOR combination was delivered through Glutamine-tagged PLGA nanoparticles (ATST + SOR/G-PLGA NPs) to promote intratumoral specificity. The formulation was optimized using DesignExpert® software by adopting Box-Behnken design (BBD). The optimized ATST + SOR/G-PLGA NPs had a spherical particle size of ~ 178.3 ± 12.6 nm, a PDI of 0.151 ± 0.08, and a Z-potential of -24.8 ± 5.8 mV. The formulation revealed a biphasic sustained release with higher release at acidic pH. In-vitro biological assessment showed a dose-dependent decrease in cell viability with reduced IC50 values. In the presence of ferrostatin-1, the IC50 value was significantly increased. The exposure to ATST + SOR/G-PLGA NPs led to elevated levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), increased late apoptotic/necrotic cells, and mitochondrial membrane depolarization. Pharmacokinetic study revealed a 2.63- and 2.93-fold improved AUC0-∞, and 2.58- and 2.84-fold improvement in MRT as compared to free SOR and ATST. Preclinical efficacy study showed a marked reduction in tumor volume and a higher inhibition rate. Toxicity assessment revealed no signs of systemic or organ toxicity, implying suitability of formulation for in-vivo delivery. In a nutshell, the proposed strategy offers a powerful avenue to manage advanced malignancies by inducing a hybrid cell death mechanism. Also, the nutrient transporter targeted polymeric nanosystems present an effective approach, which warrants further investigation.
CPT: pharmacometrics & systems pharmacologyNazanin Ahmadi Daryakenari, Mohammad Kohandel
Inverse problems in pharmacometrics and quantitative systems pharmacology (QSP) often involve sparse, noisy data, limited measurable states, and complex dynamical systems. Traditional parameter estimation methods can struggle with ill-posed problems, stiffness, discontinuities, and gray-box scenarios where only part of the system dynamics is known or observable. This tutorial provides an end-to-end, reproducible workflow for applying physics-informed neural networks (PINNs) to PK/PD/QSP inverse problems and gray-box discovery tasks. We present three worked case studies: (1) constant parameter recovery in a three-state compartmental system, (2) gray-box discovery of an unknown right-hand-side function, and (3) inference of a time-varying chemotherapy efficacy function under partial observation. For each, we provide implementation guidance, validation checks, and practical advice on collocation design, feature expansion, optimizer selection, numerical precision, constraint enforcement, loss weighting, and residual-based attention. We also discuss when to consider newer architectures such as Kolmogorov-Arnold networks (KANs) as drop-in alternatives to standard multilayer perceptrons. All code and notebooks are provided through our PhINs library, short for Pharmacometrics-Informed Networks, and are publicly available at https://github.com/NazAhmadi/PhINs/.
Animal geneticsMonica Nielsen, Hanne Gredal, Åsa Karlsson, Jennifer R S Meadows, Maja Arendt
Ivermectin-associated neurotoxicity is a potentially life-threatening condition caused by disruption of the ABCB1 encoded P-glycoprotein drug transporter in certain dog breeds. Skye terriers are considered at increased risk of ivermectin toxicity despite the absence of an identified molecular cause. We searched the Dog10K variant dataset for ABCB1 variants potentially underlying ivermectin sensitivity in Skye terriers and screened an independent cohort of 27 dogs to confirm sequence variants. A 1-bp frameshift deletion predicted to cause loss of function in ABCB1 was identified in two of three Skye terriers in the Dog10K dataset and was absent from all 1869 non-Skye-terrier genomes. The variant had an allele frequency of 16.7% in the independent Skye terrier cohort. This is the first reported ABCB1 variant in Skye terriers and represents a plausible candidate genetic basis for the anecdotally observed ivermectin sensitivity in the breed.
Pharmacoepidemiology and drug safetyI Truter, J Hugo, H Smith, S Bansal, A Vira
PURPOSE: The primary aim was to conduct a longitudinal pharmacoepidemiological study on the dispensing patterns of the influenza and pneumococcal vaccines in a section of the private healthcare sector in South Africa in the presence of the COVID-19 vaccine to document the dispensing of these two respiratory vaccines alongside COVID-19 vaccines. METHODS: A quantitative cross-sectional pharmacoepidemiological study on health insurance data covering 5 years (2017-2021) was conducted. The study population consisted of approximately 3.8 million individuals. Profile analysis was used to compare annual dispensing patterns of both vaccines. Ethical approval for the study was obtained. RESULTS: The annual dispensing patterns of the pneumococcal and influenza vaccines differed significantly for the period 2017-2021 (p-value < 0.01), with the influenza vaccine dispensed most frequently from March to June. A similar pattern was observed for both the pre-COVID-19 period (2017-2019) (p-value < 0.01) and the post-COVID-19 period (2020-2021) (p-value < 0.01). At the 5% level of significance, there was a slight increase in the dispensing pattern of pneumococcal vaccines post-COVID-19, when compared to the dispensing pattern pre-COVID-19 (p-value < 0.05). For the period March to June, there was, however, a significant increase in the dispensing pattern of influenza vaccines post-COVID-19 (p-value < 0.01). CONCLUSIONS: The presence of the COVID-19 vaccine has collectively not had a significant impact on the dispensing patterns of pneumococcal and influenza vaccines. When considering the vaccines separately, however, for the months between March and June, significantly more influenza vaccines were dispensed post-COVID-19.
Pakistan journal of pharmaceutical sciencesAmina Arshad, Muhammad Zaman, Humayun Riaz, Muhammad Sajjad Haider, Wafa Ishaq, Sherjeel Adnan, Zeeshan Masood, Hammad Ahmed, Nabeela Ameer, Hafiz Muhammad Abd…
BACKGROUND: Pitavastatin (PVN), a BCS class-II drug, exhibits poor aqueous solubility leading to limited oral bioavailability and therapeutic efficacy. OBJECTIVES: This study aimed to enhance the solubility and anti-hyperlipidemic efficacy of Pitavastatin (PVN) by encapsulating it in chitosan-based polymeric nanoparticles. METHODS: Pitavastatin-loaded chitosan nanoparticles (NPs) were prepared using the ionic gelation method. Formulations were characterized by particle size, zeta potential, drug loading, In-vitro drug release and surface morphology. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (TGA and DSC), ex-vivo intestinal permeability and in-vivo pharmacodynamic analysis were also performed. RESULTS: The size of PVN-loaded NP ranged from 219.9±1.11 to 292.7±2.29 nm with PDI 0.2-0.4, surface charge of +28.4 ± 0.43 to 32.5 ± 1.02 mV and entrapment efficiency 65±1.12-93±1.23%. Solubility in different media (PBS (pH 6.8), 0.1N HCl (pH 1.2) and distilled water showed a 56-102-fold increase compared to PVN. SEM analysis revealed a smooth surface and spherical geometry of the NP. FTIR analysis confirmed that there was no physicochemical interaction between PVN and chitosan in NP formulations (NP1-NP5). XRD and thermal analysis indicated the amorphous nature of PVN-loaded NP. In-vitro drug release from NP formulations (NPI-NP5) ranged from 80.97±4.80 to 81±3.90% indicating sustained release, while ex-vivo intestinal permeability was 1.5-fold higher than PVN. The optimized formulation (NP1) followed Higuchi release model, indicating Fickian diffusion. Pharmacodynamic analysis of lipid profiles in hyperlipidemic albino rats suggested that NP1 reduced low-density lipoprotein (LDL) by 33±1.24 %, total cholesterol by 29±2.13% and triglycerides by 23±1.21%, showing better results than PVN. CONCLUSION: Chitosan-based Pitavastatin nanoparticles successfully enhanced drug solubility and provided sustained release, leading to improved ex-vivo permeability and greater in-vivo anti-hyperlipidemic activity in albino rats. This approach represents a promising strategy for enhancing therapeutic potential of Pitavastatin.
Journal of the American Association of Nurse PractitionersLaurie M Connors
Genomics is increasingly influencing psychiatric practice as evidence links genetic variation with neurodevelopmental disorders, treatment response, and complex psychiatric presentations. Psychiatric nurse practitioners are well positioned to incorporate genomics into patient assessment and management; however, familiarity with testing options and clinical indications remains limited. This column reviews key genomic considerations for psychiatric practice, including pharmacogenomics, chromosomal microarray analysis, and exome or genome sequencing. Clinical "red flags," such as developmental delay, dysmorphic features, early-onset psychosis, epilepsy, and strong family patterns of neuropsychiatric disease, can guide decisions on when to refer for further genetic evaluation. Integrating genomics enhances diagnostic clarity, supports precision prescribing, and informs risk assessment, ultimately improving patient outcomes. Strengthening nurse practitioner genomic literacy is essential to advancing person-centered mental health care and ensuring that emerging genomic tools are applied responsibly, ethically, and effectively in practice.
Pharmacoepidemiology and drug safetyByeong Yeob Choi
BACKGROUND: In observational pharmacoepidemiology, estimating average treatment effects (ATEs) is often challenging due to a lack of practical positivity. In highly selective clinical settings, certain patients almost always or never receive treatment, causing ATE estimators to rely on unstable extrapolation. Incremental propensity score interventions (IPSIs) offer a stochastic alternative by shifting each patient's probability of treatment, providing a more clinically realistic framework that circumvents positivity violations. METHODS: We illustrate the IPSI approach, including key identification results and inferential procedures. Using observational data from a cohort of 996 patients undergoing percutaneous coronary intervention (PCI), we evaluated the effect of shifting each patient's probability of receiving abciximab by a predetermined amount on six-month mortality. Propensity scores (PSs) and outcome predictions were estimated using a machine learning ensemble (Super Learner) with 10-fold sample splitting. RESULTS: The ATE estimate suggested that abciximab administration reduced the 6-month mortality risk by 5.9 percentage points compared with PCI alone (risk difference = -0.059, 95% CI: -0.104 to -0.015). However, the practical interpretability of the ATE estimate may be limited because it implicitly assumes that patients with a near-certain probability of treatment could realistically be assigned to withhold abciximab. In contrast, shifting each patient's treatment propensity by odds ratios ranging from 0.1 to 10 showed that 6-month mortality would be significantly reduced under a strong treatment policy promoting abciximab administration. CONCLUSIONS: IPSIs provide a robust and practical alternative to conventional causal inference methods in pharmacoepidemiology settings where treatment assignment is highly selective and the strict positivity is violated.
Pharmacoepidemiology and drug safetyJames M Gwinnutt, Rodrigo de Oliveira, Miriam J Haviland, Julien H Shippee, Elizabeth Eldridge, Lenon Mendes Pereira, Emily Bratton, Jay Nanavati, Christina De…
Large language models (LLMs) represent a type of generative artificial intelligence (GenAI) that generate and interpret text, with some LLMs able to process multimodal content (e.g., images, audio, video), and can be deployed as part of agents to perform users' tasks. LLMs can perform natural language processing functions such as summarization, translation, and extraction giving them the potential to enhance and scale pharmacoepidemiological and real-world research by performing tasks such as literature review, data extraction, and medical writing. Despite the growing integration of GenAI tools into research workflows, their technical foundations and methodological implications remain unfamiliar to many pharmacoepidemiologists, who are often responsible for the reliability and accuracy of research that relies on these tools. This paper aims to inform pharmacoepidemiologists about the capabilities and limitations of LLMs to support responsible integration into the field of pharmacoepidemiology, providing an intuitive overview of how LLMs work, focusing on training and text generation, and reviews current and emerging applications in drug effectiveness and safety research and epidemiology. The article addresses challenges associated with LLM use in real-world evidence generation, including concerns regarding reproducibility, bias, hallucinations, plagiarism, data privacy, and the need for validation.
Health expectations : an international journal of public participation in health care and health policyJulie Rigoureau, Manon Verroul, Valentine Vieillard, Anne Termoz, Laurie Panse, Anaïs Havet, Marie Viprey, Julie Haesebaert
BACKGROUND: Patient and public involvement in pharmacoepidemiology using healthcare administrative databases remains limited despite its potential to enhance research relevance and societal impact. We evaluated the feasibility and benefits of involving patients as research partners in a Patient Committee for a pharmacoepidemiological study using the French nationwide health insurance database (SNDS). METHODS: A participatory feasibility study was conducted through the establishment of a Patient Committee alongside the study's Scientific Committee. A mixed-methods evaluation assessed feasibility combining quantitative indicators, analysis of group dynamics, and thematic analysis of the transcription of the second meeting. Benefits were evaluated based on changes made in protocol, statistical analysis, and civil society dissemination plans based on patients' proposals. The McMaster tool was used to assess the involvement process. RESULTS: Three patients were recruited out of the minimum expected five. Of the five meetings, three were attended by all participants. Consensus was reached on most points discussed and a good cohesion was observed within the Committee. The questions asked to the moderators focused primarily on the progress of the research and on the availability of data beyond the reimbursement-related data available in the SNDS, as data related to the patient's perspective (quality of life or anxiety). At the second meeting, only 13% of coded exchanges fell within the categories previously predefined according to the meeting's objectives. The remaining themes were unrelated to their illness, drug utilisation or care pathways. Patient involvement led to an effective modification of a primary outcome in the research protocol and an additional statistical analysis. Patient Committee also contributed several points for discussion and produced two visual abstracts. Finally, patients expressed satisfaction with their participation, feeling that their opinions had been listened to and taken into account. Project team members involved in project management appeared satisfied with the process, except in logistical needs (very long research timeline with specific deadlines to be met). CONCLUSION: Although benefits of patient involvement were observed, feasibility was partial due to several obstacles related to participant recruitment and patients' understanding of the SDNS. To improve feasibility, future initiatives should co-construct appropriate methodologies with stakeholders and provide adequate training tailored to the complexity of pharmacoepidemiology research. PATIENT AND PUBLIC CONTRIBUTION: The study was conducted in collaboration with the patient partner from the research laboratory. She was involved in recruiting the Patient Committee and drafting the recruitment materials (flyer and email). The patient partner also proofread the content of the training session.
The pharmacogenomics journalNajmeh Ahangari, Mohammad Doosti, Mojtaba Safi, Narges Hashemi, Shima Imannezhad, Bita Barazandeh, Ehsan Ghayoor Karimiani, Mehran Beiraghi Toosi
Epilepsy is a diverse and often severe neurological disorder characterized by frequent and unpredictable seizures caused by the simultaneous discharge of brain cells in one or both hemispheres. Recently, there has been a significant shift in the approach to healthcare, moving from a standardized model to a more personalized and targeted model. This transformation has been made possible by advances in pharmacogenomics. It has great potential in customizing treatments based on the specific needs of patients, and this is particularly evident in the management of epilepsy. With ongoing research, the development of comprehensive genetic databases, and the integration of pharmacogenomics into clinical practice using artificial intelligence, a brighter future can be expected for personalized epilepsy treatment. Using the potential of pharmacogenomics, we can expect to provide the best possible care for epilepsy patients and improve their quality of life.
In today's world, research has evolved a lot in the field of cancer and docetaxel (DTX) has been intensively studied for its ability to cure different types of cancers. However, the intravenous delivery of DTX puts forth various undesirable side effects, while oral delivery has its own solubility and permeability drawbacks. The advancements in research have focused on overcoming these disadvantages by developing novel and efficient DTX-based drug delivery systems. The review aims at identifying challenges faced by DTX and thereby forecasting the different DTX formulations established to surpass them. The successful DTX delivery is mediated by certain efficient nanocarriers, inclusion complexes, etc., effectively destroying the cancerous cells. The current clinical status of these formulations has also been listed in this review. The dedicated efforts of researchers have been fruitful in site-specific targeting of DTX by novel formulations, thus enhancing its antitumor effect. However, this success has been restricted only to preclinical studies and only a few formulations have entered the CTs, while none have received market approval. A deep understanding of the basics of nanoformulations, along with their toxicological insights and flexible production procedures, will help to combat the clinical hurdles faced by them.
AAPS PharmSciTechRaghda Abd El Moneum Ali Abdel Mawla, Wedad Sakran, Fares Ibrahim Farag Masry, Mohammed Salah Ahmed Teiama
This study was designed to develop and optimize a thermosensitive intranasal gel incorporating temozolomide (TMZ) and N-acetylcysteine (NAC) as a promising platform for direct nose-to-brain drug delivery. Formulations were fabricated via cold technique utilizing Carbopol 934P and poloxamer 407 to improve gelation and mucoadhesion. After evaluating the formulations for clarity, pH, gelation temperature, gelling time, mucoadhesion, and drug loading, the formula A13 was elected as the optimized formulation based on a factorial design optimization approach. The optimized formula was further evaluated for stability, ex-vivo permeability, histopathology and in-vivo pharmacokinetic in rats. Compared with the corresponding in-situ gels containing the pure drugs, formulation A13 enhanced the ex-vivo nasal mucosal permeation of TMZ and NAC by 1.42-fold and 1.64-fold, respectively, indicating the superior permeability-enhancing effect of A13. Furthermore, histopathological examination revealed no evidence of structural damage following administration of formulation A13, confirming its safety for intranasal application. The in-vivo studies performed on rats showed significantly higher Cmax and AUC 0-24 results in brain of the optimized A13 by 1.4, 1.4, 2.6 and 1.87 folds in TMZ and NAC, respectively compared to in-situ gel of pure TMZ and in-situ gel of pure NAC, with a delayed (Tmax). The brain-to-blood concentration ratios of the TMZ-NAC-loaded in-situ gel were consistently higher than those of the pure-drug in-situ gels at most sampling time points, indicating more efficient nose-to-brain transport. Overall, these findings demonstrate that the optimized A13 is a promising and safe intranasal delivery system for enhancing the nose-to-brain delivery and bioavailability of TMZ and NAC.
Burn wound infections remain a major clinical challenge due to extensive tissue damage, delayed healing, and increased susceptibility to microbial contamination, which can limit the effectiveness of conventional topical formulations. This study aimed to develop and optimize a Quality-by-Design (QbD)-based non-propellant foam (NPF) containing silver nitrate, chlorhexidine, and asiaticoside for enhanced burn wound management. A sequential design of experiments strategy was employed, involving Taguchi L8 screening followed by Box-Behnken optimization to identify the critical formulation variables influencing foam performance and drug release. The optimized formulation exhibited desirable physicochemical characteristics, including a foam density of 0.192 ± 0.002 g/mL, a skin-compatible pH of 5.56 ± 0.04, uniform drug content (98-99%), and satisfactory foam stability. In-vitro studies demonstrated cumulative drug release of 94.69% chlorhexidine, 82.13% asiaticoside, and 78.63% silver nitrate within 6 h, with the release profiles predominantly following the Higuchi diffusion model. Accelerated stability studies indicated that the formulation remained stable over six months. In a Sprague-Dawley rat burn wound model, the optimized foam achieved 93.29 ± 1.75% wound contraction by day 14, outperforming both the untreated control and the marketed formulation. Furthermore, biochemical analyses revealed increased hydroxyproline, hexosamine, and hexuronic acid levels, while histopathological examination confirmed enhanced collagen deposition, neovascularization, and re-epithelialization. These findings demonstrate that the developed QbD-based non-propellant foam represents a promising preclinical topical delivery platform capable of supporting both antimicrobial protection and tissue repair during burn wound healing.
AAPS PharmSciTechAawaz Raj Pokhrel, Jayanti Das, Boren Ke, Lisa Ma, Shawn Zhang, Maxwell Korang-Yeboah
Microstructural characterization of pharmaceutical drug products is essential for understanding process-microstructure-performance relationships and ensuring consistent product quality. However, quantitative characterization is limited by a trade-off between imaging resolution and field of view: high-resolution imaging captures fine structural detail but over small sample volumes, whereas lower-resolution imaging provides broader coverage while missing critical morphological features. To address this limitation, we developed and validated an integrated framework combining convolutional neural network (CNN)-based super-resolution with Generative Adversarial Network (GAN)-based microstructure synthesis. Lyophilized drug products imaged by X-ray microscopy at multiple resolutions served as the model system. We first demonstrated that imaging resolution is a governing factor in quantitative microstructural analysis: mean pore size showed a coefficient of variation of 40.2% across resolution levels, compared with only 0.47% attributable to spatial heterogeneity within the same sample. CNN-based upscaling using ESRGAN/BSRGAN recovered solid-wall structures and pore-size distributions lost after downsampling and restored effective diffusivity toward values measured in the original high-resolution data. In an independent validation using a separate formulation imaged at 5 and 10 µm per voxel, the upscaled images reproduced pore-size distributions and diffusivity profiles closer to the 5 µm reference and showed better recovery of CQA-relevant structural features than conventional bicubic interpolation, despite lower pixel-level image fidelity scores. GAN-based synthesis expanded the field of view four-fold from a small high-resolution seed region while preserving pore-size distributions and transport properties. Together, these findings demonstrate a scalable approach for improving microstructural characterization under practical imaging constraints.
In vitro dissolution testing is central to pharmaceutical development, yet it is increasingly challenged by poorly soluble drugs, which account for over 40% of marketed products and up to 90% of new chemical entities, for which dissolution often limits absorption. Surfactants are widely incorporated into dissolution media to achieve sink conditions and improve the discriminatory powder of dissolution methods, but inappropriate surfactant selection or concentration can alter drug release mechanisms, mask formulation differences, and reduce biopredictive performance. This review examines the mechanisms of surfactant action, including wetting enhancement, micellar solubilization, and drug-surfactant interactions, together with the physicochemical properties of anionic, cationic, non-ionic, and zwitterionic surfactant relevant to dissolution testing. Building on these principles, we discuss practical considerations for surfactant selection, concentration optimization, analytical compatibility, surfactant quality and source variability, formulation-specific considerations for enabled drug delivery systems, integration with physiologically based biopharmaceutics modeling, and evolving regulatory expectations. Together, these provide a practical framework for developing robust, reproducible, and discriminating dissolution methods that better reflect in vivo performance and support decision-making across drug development.
AAPS PharmSciTechMagdi E A Abobaker, Mershen Govender, Yahya E Choonara
The therapeutic efficacy of interferon alpha (IFNα) is well-established in various conditions, including Hepatitis B and C, lymphoma and skin cancer, attributed to its potent angiostatic, immunomodulatory, and antiproliferative properties. Clinical applications using this bioactive are, however, hindered by systemic toxicity due to the high doses used, increasing costs and reducing patient adherence. The use of a controlled-release polymeric nanoparticulate system that can potentially decrease the administered dose, and therefore the associated costs, may additionally improve overall patient acceptability without affecting therapeutic efficacy. This study provides for the development, statistical optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles (PLGANPs) for the controlled release of IFNα. A double-emulsion solvent evaporation method was employed for nanoparticle (NP) synthesis, with formulation optimization achieved through a Central Composite Design (CCD) approach to ensure adequate size, stability, and sustained release over five days. Characterization of the optimized IFNα-PLGANPs using dynamic light scattering, zeta potential analysis, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and drug release studies at pH 7.2 displayed an average particle size of 97.03 nm (PDI = 0.182), zeta potential of - 34.10 mV and a maximum drug release of 5 days, with morphological analysis revealing the formation of spherical NPs with a smooth surface topology, confirming the homogeneity and structural stability of the formulation. These findings underscore the potential of the developed PLGANPs as a suitable platform for the controlled release of IFNα, noting the use of advanced nanotechnology-driven solutions to overcome the limitations of conventional therapies.
Statins are widely regarded as the gold standard first-line treatment for hyperlipidemia, as they inhibit HMG-CoA reductase in the liver. This effectively reduces LDL cholesterol levels and reduces cardiovascular risks, such as heart attack and stroke. Simvastatin is a well-established, effective, and cost-efficient statin for lowering LDL cholesterol and reducing cardiovascular risk. However, it causes myopathy, rhabdomyolysis, myalgia, constipation, kidney failure, headache, abdominal pain, diarrhoea, nausea, and increased blood sugar levels with its use and higher doses of 80 mg/day. To address this, a liposomal simvastatin formulation with particle sizes of 150-250 nm was developed for intravenous administration. This formulation can potentially accumulate in the liver via passive targeting via the RES, thereby enhancing hepatic uptake and improving safety. The liposome was formulated using the thin-film hydration method and optimised using a central composite design. The optimized formulation's vesicle size was 204.66 ± 2.84 nm, with a PDI of 0.27 and a zeta potential of -58.11 mV, indicating uniform distribution and high stability. In-vitro drug release demonstrated controlled release of up to 92.46% over 60 h. The cellular toxicity assay showed that the optimized liposome was 10 times safer than pure simvastatin. In-vivo, the liposomal formulation significantly reduced lipid levels after administration of a 5 mg/kg dose in Triton X-100-induced hyperlipidemic rats, outperforming marketed formulations and standard drugs. Simvastatin-liposomes are safe, stable, and a more potent alternative to traditional oral simvastatin, offering improved liver targeting and a reduced toxicity profile.
AAPS PharmSciTechMariame A Hassan, Bhanu Prakash Dongala, Annette DeSantiago, Ziyaur Rahman, Mansoor A Khan
Divalproex Sodium (DVS) is an antiepileptic agent with a narrow therapeutic window and a wide range of side effects. Its delayed-release forms demonstrated better tolerability in terms of gastrointestinal side effects. DVS has high sensitivity to temperature and humidity. Owing to a high frequency of daily administration, outpatients may keep their medication supply accessible in places that might not qualify for proper drug storage. In this study, five FDA-approved DVS delayed-release tablet products (A-E) were assessed for physical integrity, physicochemical changes and drug release pattern before and after repackaging in amber-colored closed pharmacy vials and storage at 30°C/75%RH. Initially, one product showed dissimilarity to the others (f1 = 19.6, f2 = 41.6). Upon storage, tablets showed signs of physical damage after 1 month. At 3 months, A, B and E tablets lost their integrity completely. Product C displayed high variability in acid (44.9 ± 31.5% drug release). Tablets that remained intact after storage failed the f1 and f2 tests. The images showed evidence of chemical changes in all products. The results indicated that repackaging and improper in-use keep could result in unpredictable drug release. It is debated that the total daily systemic bioavailability of DVS, rather than the peak-to-trough differences, is the primary determinant of seizure control. However, variability in drug release can result in gastric irritation, systemic side effects, drug intolerance and patients' noncompliance. This unnecessary burdening of the health care system can be avoided when revising dispensing and storage recommendations of DVS products.
ChemMedChemPascal Heitel, Philipp Barbie, Alessia Gambardella, Marta Pinto, Felix Pape, Anika Tarasewicz, Gerhard Hessler, Bernhard Wünsch, Matthias Schiedel, Christina L…
The Frontiers in Medicinal Chemistry (FiMC) was held in Münster from March 24th to 27th as the largest international Medicinal Chemistry conference in Germany. Welcoming more than 240 participants from around 20 countries, it was a vibrant conference, celebrating the community and the Medicinal Chemistry division of the German Chemical Society (GDCh). The program filled 4 days with over 40 lectures from industry and academia, and 125 posters. Herein, the NextGenMedChem group reports their highlights from this conference.
BMC complementary medicine and therapiesAhmed Zayed, Meryem El Jemli, Mourad Kharbach, My El Abbes Faouzi, Rasha Ali Radwan, Shahira M Ezzat
BACKGROUND: Traditional Moroccan herbal teas are widely consumed and have been traditionally used for managing chronic metabolic disorders, particularly type 2 diabetes mellitus (T2DM). Although these preparations have a long history of ethnomedicinal use, their phenolic composition and biological activities remain insufficiently characterized. Scientific validation is needed to support their traditional application and provide evidence for their potential relevance to T2DM management. This study aimed to characterize the phenolic profile, antioxidant potential, and carbohydrate-digestive enzyme inhibitory activity of 21 traditional Moroccan herbal teas used for glycaemic control. METHODS: Phenolic constituents were identified and quantified using HPLC-MS. Antioxidant capacity was evaluated through DPPH, ABTS, and FRAP assays. Inhibitory effects on α-amylase and α-glucosidase were assessed in vitro. Correlation analyses were conducted to explore associations between phenolic constituents and biological activities. FINDINGS: Marked variability in total phenolic content (TPC) was observed, with Mentha × piperita and Thymus broussonetii exhibiting the highest levels at 883.2 ± 13.0 and 746.8 ± 22.4 mg GAE/g dry weight, respectively. Antioxidant activity varied substantially among the investigated teas, with T. broussonetii (FRAP reducing power: 423.6 ± 9.8 µg/mL) and Mentha rotundifolia (162.6 ± 0.6 µg/mL) showing significant reducing capacities. TPC exhibited strong positive correlations with antioxidant indices (r = 0.93-0.96). Pelargonium graveolens presented potent α-amylase inhibition (IC50 = 2.98 ± 1.7 µg/mL), whereas Mentha viridis and Calamintha officinalis were among the most active α-glucosidase inhibitors (IC50 = 1.9 ± 0.4 and 1.2 ± 0.1 µg/mL, respectively). Negative correlations were found between rutin (r = - 0.49) and gallic acid (r = - 0.44) contents and α-amylase IC50 values. CONCLUSION: The investigated Moroccan herbal teas exhibited variable antioxidant and digestive-enzyme inhibitory activities that were associated with their phenolic composition. Variability among samples may reflect differences in plant species and environmental or agronomic factors. These findings provide comparative in vitro evidence supporting the traditional use of Moroccan herbal teas and highlight several species as promising sources of bioactive phenolics. However, the present findings do not establish therapeutic efficacy, and further in vivo, mechanistic, pharmacokinetic, and clinical studies are required to confirm their efficacy, safety, and clinical relevance.
European journal of clinical pharmacologyChangsong Wu, Xiangyi Yuan, Yanling Pan, Jing Yang, Bin Zhao, Longkuan Li
PURPOSE: Valproic acid (VPA) is one of the most commonly prescribed broad-spectrum antiseizure medications for pediatric epilepsy. However, substantial interindividual variability exists in therapeutic efficacy and hepatotoxicity during VPA treatment, and reliable biomarkers for individualized prediction remain limited. This study aimed to identify metabolomic biomarkers associated with VPA therapeutic response and hepatotoxicity in pediatric patients with epilepsy and to construct integrated metabolomic-genomic prediction models for VPA efficacy and hepatotoxicity. METHODS: A total of 194 pediatric epilepsy patients receiving VPA monotherapy were enrolled in this study. Untargeted metabolomics analysis was performed using LC-MS/MS to identify endogenous metabolites associated with VPA therapeutic efficacy and adverse reactions. Differential metabolites were analyzed using principal component analysis, volcano plot analysis, hierarchical clustering, and metabolite enrichment analysis. Candidate SNPs identified in our previous pharmacogenomic study were further integrated with metabolomic features for multi-omics modeling analysis. Logistic regression analysis was used to construct prediction models, and model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, confusion matrix analysis, and bootstrap internal validation. RESULTS: Untargeted metabolomics analysis identified multiple differential metabolites associated with VPA therapeutic response and hepatotoxicity. Differential metabolites related to VPA efficacy were mainly enriched in pyrimidine metabolism, vitamin B6 metabolism, pantothenate and CoA biosynthesis, and beta-alanine metabolism pathways. Differential metabolites associated with hepatotoxicity were primarily enriched in arginine biosynthesis, pyrimidine metabolism, purine metabolism, and steroid hormone biosynthesis pathways. Integrated metabolomic-genomic prediction models demonstrated good predictive performance. For VPA therapeutic response, the combined model achieved an AUC of 0.830 in the training set and 0.817 in the testing set. For VPA-related hepatotoxicity, the model achieved an AUC of 0.816 in the training set and 0.791 in the testing set. Calibration curve and confusion matrix analyses further demonstrated acceptable robustness and predictive capability of the models. CONCLUSION: This study identified multiple endogenous metabolites and metabolic pathways associated with VPA therapeutic efficacy and hepatotoxicity in pediatric epilepsy patients. Integration of metabolomic and pharmacogenomic features may improve individualized risk stratification of VPA treatment outcomes; however, prospective multicenter external validation and clinically standardized metabolite assays are required before these models can be implemented in routine pediatric epilepsy care.
Human PTGS1 and PTGS2 encode cyclooxygenase paralogs that regulate prostaglandin biosynthesis and are major targets of nonsteroidal anti-inflammatory drugs (NSAIDs). Interpreting population-differentiated PTGS variation requires integration of allele-frequency structure with transcript consequence, protein topology, splice-prediction evidence and structural context. This study integrated allele-resolved population differentiation, transcript-aware consequence annotation, splice-prediction boundary checks, protein-domain mapping, direct leader-sequence property calculations and controlled structural analyses. Candidate classes distinguished high-FST synonymous contextual markers, N-terminal PTGS1 leader-sequence missense variants, splice-region candidates and PTGS2 p.Val511Ala. Web-based SpliceAI/Pangolin evaluation of seven splice-relevant or comparator variants provided limited support for splice alteration. A retrospective comparison of 31 missense candidates showed that Val511Ala was not the most differentiated missense variant overall, but ranked first by allele frequency, allele-frequency range and maximum pairwise FST within four channel-context candidates; FST was used only to describe population differentiation. Canonical Val511 mapped to 5KIR Val525, a second-shell position adjacent to the rofecoxib-contact network. Controlled docking-score, contact and direct-frame pose analyses detected no systematic variant-associated shift under the tested conditions. PTGS1 p.Trp8Arg and p.Pro17Leu produced distinct directly calculated changes in net-charge proxy, hydrophobic-residue count, mean Kyte-Doolittle hydropathy, aromatic-residue count and proline count across the 23-residue leader sequence and descriptive H-region. No signal-peptide predictor output was used, and effects on SRP recognition, ER targeting, translocation, cleavage, membrane insertion, maturation, abundance, localization, enzyme activity or drug response were not demonstrated. These results support a calibrated prioritisation framework in which population differentiation identifies structured variation, while transcript consequence, protein context and reproducible quantitative analyses define experimentally testable candidates.
The New England journal of medicineDavid J Hunter, Michael Inouye
Twenty-five years after the draft of the human genome sequence, genomics has revolutionized many areas of biology, the diagnosis of familial and early-onset diseases, and the development of targeted therapies, particularly in oncology. Genomic knowledge has had little effect on the diagnosis and treatment of most common adult-onset conditions. Genomewide association studies have revealed that for these conditions, thousands of genetic variants of small effect underpin the polygenic nature of risk. When incorporated into polygenic risk scores, these variants predict risk; however, polygenic risk scores have had little effect in the clinic. In this article, we review the reasons for the slow pace of the diffusion of these methods in clinical practice. With the impending era of relatively inexpensive genome sequencing in mind, we review the ways in which polygenic risk scores, along with the related field of pharmacogenomics, may be useful in clinical practice for the prevention and treatment of common diseases.
Real-time quality control of pharmaceutical dosage forms requires rapid, non-destructive analytical technologies that provide chemical specificity while maintaining high throughput. Here, an extended short-wave infrared (eSWIR, 1000-2500 nm) line-scan hyperspectral imaging system (L-EOS 2.5e, Photon Etc.) was evaluated for spatially resolved classification of pharmaceutical tablets. The system was evaluated at integration times of 2, 0.2, and 0.02 ms using Standard Normal Variate normalization, Savitzky-Golay second-derivative preprocessing, and an error-correcting output codes support vector machine classifier. Product-level classification of 11 pharmaceutical products achieved accuracies of 99.99%, 100%, and 97.6% at 2, 0.2, and 0.02 ms, respectively. A more challenging manufacturer-level discrimination task involving three 500 mg acetaminophen products containing the same active pharmaceutical ingredient and labeled dose achieved accuracies of 99.7%, 98.6%, and 89.3% at the corresponding integration times. These results demonstrate the potential of eSWIR hyperspectral imaging for rapid, spatially resolved pharmaceutical product discrimination and high-throughput inspection.
AAPS PharmSciTechShang-Yin Wu, Yun-Jie He, Ci Qian, Si-Ru Zhong, Hong-Xing Xiao, Changyun Xiong, Bin Di, Wei-Jie Fang
High-concentration protein formulations for subcutaneous administration have developed rapidly, while viscosity-related pipetting errors remain a key bottleneck for accurate protein concentration quantification, with commercial detection instruments showing significant limitations in direct measurement of these samples. Here, we developed two pipetting-optimized quantification strategies using two high-concentration monoclonal antibody formulations with distinct viscosities as models: a motorized continuous pipette-based direct measurement method and a weight-corrected method. We validated the high accuracy and repeatability of the motorized continuous pipette for high-viscosity liquid handling, and systematically compared the performance of our optimized methods with the traditional manual pipetting method and three mainstream commercial protein analyzers. Direct measurements using the three evaluated analyzers showed formulation-dependent deviations under the tested conditions. Both optimized workflows improved pipetting precision and provided concentration estimates with improved repeatability for the two high-concentration mAb formulations examined. These findings support motorized pipetting and weight correction as practical options when viscosity compromises volumetric transfer, while their applicability to other protein modalities and formulations with intermediate viscosity requires further validation.
Polymeric nanospheres are promising drug delivery systems capable of controlling the release of active molecules. However, their inherent colloidal instability necessitates the use of drying techniques to enhance physicochemical stability and microbial resistance. However, conventional multi-step production processes hinder industrial-scale-up due to increased complexity and longer processing times. This work aimed to develop a single-step spray-drying process to obtain Eudragit® L100 nanospheres in powder form, thereby eliminating the need for traditional solvent evaporation, and to investigate the effects of incorporating these nanospheres into hydroxyethyl cellulose gels for dermatological applications. Eudragit® L100 was selected for its controlled release at approximately pH 6.00, facilitating delivery to specific areas, particularly on barrier-disrupted skin. Nanospheres were produced via nanoprecipitation followed by direct spray-drying to reduce production time. The nanosuspension and redispersed dried formulations were characterized by particle size, polydispersity index, morphology, and zeta potential. Before drying, the nanospheres had an average size (Z-average) of 114 nm and a polydispersity index (PdI) of 0.19 and successfully preserved their properties after a single drying step (Z-average = 140 nm and PdI = 0.2). Zeta potential was altered (p < 0.05) but remained high (-23 to -17 mV), indicating electrostatic stabilization. Gel formulations exhibited dose-dependent pseudoplastic behavior, with consistency decreasing proportionally to nanosphere concentration. Finally, moderate to strong correlations were found between rheology and textural analysis. This single-step solvent removal methodology represents a significant manufacturing advancement, offering reduced processing time and costs. The pH-responsive nanospheres showed excellent redispersibility and gel compatibility, establishing their potential as carriers for dermatological systems.
AAPS PharmSciTechGabriel S Oliveira, Ana Luiza Lima, Pedro Granados Muñoz, Idejan P Gross, Livia Sa-Barreto, Patrícia Medeiros-Souza, Tais Gratieri, Guilherme M Gelfuso, Marcil…
Pediatric maintenance therapy for acute lymphoblastic leukemia requires prolonged daily administration of 6-mercaptopurine (6-MP), a drug characterized by a narrow therapeutic index and substantial interindividual variability, creating a need for flexible and patient-friendly dosage forms. This study aimed to develop pediatric chewable tablets 6-MP using hot-melt extrusion and fused deposition modeling (FDM) 3D printing. Preformulation studies and rheological characterization were performed to support formulation development. The influence of internal architecture on porosity, disintegration, mechanical properties, and chewability was investigated by varying infill density. Among the evaluated architectures, 30% infill provided the best balance between structural integrity, porosity, rapid disintegration, and softening after saliva exposure, ensuring adequate chewability. Tablets exhibited accurate drug content (99.5 ± 2.2%). Beyond their immediate-release behavior, complete drug release was achieved within 15 min, while colloidal nanostructures were spontaneously formed, associating approximately 11% of dissolved 6-MP, suggesting a hybrid release mechanism combining rapid drug availability with nano-mediated modulation. Dynamic light scattering and transmission electron microscopy confirmed these findings. Overall, the developed platform demonstrates the potential of FDM-based structural engineering to produce personalized pediatric medicines and reveals that thermally processed polymeric matrices may function as dynamic drug delivery systems rather than conventional immediate-release dosage forms.
AAPS PharmSciTechParoma Chakravarty, Minhthi Bui, Kellie K Sluga, Bifan Chen, Simon Chan, Hao Helen Hou
GENE-A, a small molecule classified as a BCS Class IV compound, was formulated as a spray dried amorphous solid dispersion (SDD) using HPMC-AS polymer for oral delivery and compressed with additional excipients to yield tablets. Owing to a high clinical daily dose projection, the possibility of administering multiple tablets in applesauce was explored for patient compliance. Since GENE-A crystallized to a hydrate in aqueous media in previously conducted solubility studies, dispersion of SDD tablets in applesauce (aqueous medium) necessitated the development of an analytical method to detect low levels of crystallinity in these mixtures. Using transmission PXRD and multistep sample preparation procedure, a calibration curve was obtained by employing powder blends with matching composition as SDD tablets, spiked with different amounts of crystalline hydrate, dispersed in applesauce. From this curve, the limits of detection and quantitation of crystalline active in these samples were determined to be 1.8 and 4.9% respectively. A 8.5-12% error of prediction for % crystallinity was obtained for validation samples which may be attributed primarily to sample preparation challenges such as retention of water in the centrifuged samples. Using this method, % crystallinity was determined to be < LOD in the test samples, i.e. film coated SDD tablets (for clinical use) dispersed in applesauce at T = 0 and 2 h. Our study is the first to demonstrate the development of a PXRD based method for detecting low levels of crystallinity in a semi-solid matrix to monitor physical stability of an active in drug-vehicle mixtures.
This study aimed to enhance the physicochemical properties of curcuminoids by preparing an inclusion complex and formulate an orodispersible tablet (ODT) suitable for elderly patients. A purified curcuminoid was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). A design of experiments was employed to optimize the formulation by investigating the effects of a binder and a superdisintegrant on critical tablet attributes. The final optimized ODT was evaluated for compliance with pharmacopeial standards. The 1:1 molar ratio curcuminoid:HP-β-CD complex was identified as optimal, providing a substantial (214-fold) increase in solubility. The complex demonstrated superior photostability, thermal resistance, and ambient storage stability compared to the uncomplexed curcuminoid. The optimized ODT formulation, exhibited excellent mechanical robustness and achieved a rapid disintegration time of 22.21 ± 1.94 s. In vitro dissolution studies showed enhanced drug release, achieving 97.79 ± 0.66% release at 60 min and demonstrating a distinct dissolution profile compared to a commercial non-complexed formulation. This work presented a rational, dual-strategy formulation approach that combines molecular-level solubility enhancement with dosage form optimization to improve the in vitro performance of curcuminoids. The findings highlight the potential of cyclodextrin-based ODT systems as a scalable platform for delivering poorly soluble phytochemicals, particularly for geriatric and dysphagic populations.
AAPS PharmSciTechAnroop B Nair, Mohamed A Morsy, Ahmed M Agiba, Rofida Albash
Terpenes have a low potential for irritation and are classified as Generally Recognized as Safe (GRAS) chemicals. Terpenes possess favorable biological properties that support their use in drug delivery. Some terpenes and essential oils have been encapsulated in nanostructured systems called terpesomes to overcome their chemical instability. Compared to conventional vesicles, terpesomes are new vesicular structures that showed greater membrane penetration. The capacity of terpesomes to increase permeability across membranes while decreasing systemic absorption is one of their main benefits. Terpesomes enhance drug permeation by improving membrane interaction and increasing drug transport across biological barriers. The structure, characterization, penetration processes, and applications of terpesomes are all addressed in this review. Overall, this review highlights that the enhanced penetration capability of terpesomes makes them promising lipid vesicular carriers for a wide range of pharmaceutical applications.
International journal of molecular sciencesTommaso D'Anna, Angelo Montana, Giulia La Magna, Marco Piraino, Antonella Pecorella, Maria Giovanna Scioli, Sonia Terriaca, Beatrice Belmonte, Augusto Orlandi,…
Interpretation of opioid-related toxicity and death requires integration of exposure, measured toxicology, individual susceptibility, and alternative causes. We systematically reviewed human pharmacogenetic/pharmacogenomic (PGx) and multi-omic studies published from 1 January 2008 to March 2026, identified through MEDLINE/PubMed, Scopus, and Web of Science Core Collection. JBI tools informed risk-of-bias assessment, and findings underwent effect-size-oriented narrative synthesis and descriptive mapping. The 75-study corpus was predominantly PGx (51 studies, 68.0%); only 17 studies addressed transcriptomic/epigenetic, metabolomic, proteomic, or integrated approaches, and seven retained other molecular classifications. These domains therefore differ substantially in evidential maturity. The most coherent PGx findings concerned CYP2D6-dependent codeine and tramadol bioactivation, CYP2B6-dependent methadone disposition, and ABCB1-related tissue distribution. Omics findings were exploratory, with limited external validation and specificity for fatal causation; proteomics rested on a single investigation. Forensic interpretative directness was high or moderate in 36 studies and low or absent in 39. No nitazene-specific study met this review's molecular eligibility criteria. Certainty was very low for the four outcome-focused bodies assessed with GRADE; integration utility and confounder control were appraised narratively. Molecular findings may explain discordance between inherited susceptibility, parent-drug/metabolite patterns, and the observed phenotype. Downstream signatures may also reflect chronic exposure, terminal hypoxia, or postmortem change. Neither the descriptive evidence-map scores nor individual molecular markers provide validated estimates of forensic risk or establish cause of death independently.