Medicine and Pharmacology

Abstract: (1) Objective: This study aims to evaluate the pre-admission pharmacist for high-risk obstetric patients’ admissions on medication management processes, workflow efficiency, and staff satisfaction. (2) Methods: Data collected over a 12-month period, from March 2025 to February 2026, were analysed. Data collected included clinic type, patient attendance, mode of pharmacist review, and follow-up requirements. Multidisciplinary healthcare professionals were invited to complete a satisfaction survey to identify themes relating to service value, workflow impact, and opportunities for improvement. (3) Results: A total of 1039 interviews with obstetric patients equating to an average of 19.98 interviews per week. A total of 999 patients were involved in the 1039 interviews held, 40/999 (4%) patients required additional follow-up telephone interview and 14 patients (14/999, 1.4%) requiring in-person interview for interpreter services, detailed discussion or hearing impairment. Thirty-two staff responded to a survey and demonstrated a consistent trend across anaesthetists, nursing and midwifery staff and pharmacists. All respondents either agreed or strongly agreed that PAC pharmacist in obstetric setting was valuable and beneficial to clinical workflow and medication management processes, and that they were satisfied with the PAC pharmacy service. (4) Conclusion: The PAC pharmacist demonstrated a positive impact on medication management for obstetric patients within the pre-admission setting.

Abstract: Background / Objectives: Colorectal cancer is a leading cause of global cancer-related mortality. Capecitabine, a 5-fluorouracil prodrug, effectively targets colorectal cancer but suffers from an extremely short half-life, requiring frequent administration. Bilosomes (membrane-stabilized bile salts) are vesicular systems that improve gastrointestinal stability, prevent drug leakage, and extend residence time. This study aimed to develop capecitabine-loaded bilosomes to overcome these pharmacokinetic drawbacks and enhance therapeutic efficacy. Methods: In a 3² full factorial design, nine capecitabine-loaded bilosomes were generated utilizing a central composite design within the framework of response surface methodology. Entrapment efficiency, in vitro drug release, and its kinetics vesicle size, zeta potential, and their kinetics were evaluated. The optimized capecitabine-loaded bilosomes formulation was exposed to further investigations, such as ATR-FTIR, DSC, X-ray diffractometry study, stability studies, pharmacokinetic study, and in vivo studies, including detection of matrix metalloproteinase-9 and vascular endothelial growth factor A by Real-Time polymerase chain reaction, evaluation of colon biomarker, and examination of colon tissue through histopathology. Results: The prepared capecitabine-loaded bilosomes were nanosized spheres with suitable entrapment efficiency and a high zeta potential. After treatment with capecitabine-loaded bilosomes, the data collected from living organisms indicated a notable reduction in the serum value of carbohydrate antigen 19.9 and cancer embryonic antigen, gene expression values of matrix metalloproteinase-9, and vascular endothelial growth factor A. Histopathological study showed almost restoration of colonic features with a lesser extent of epithelial lining and crypt dysplasia. Conclusion: The present study findings demonstrate that capecitabine-loaded bilosomes possess high anti-tumor activity against colorectal cancer.

Abstract:

Angiotensin II (AngII) binds to the AngII type 1 receptor (AT¹R) in either A-mode (on-switch; G-protein-mediated contraction) or D-mode (off-switch; arrestin-mediated desensitization/tachyphylaxis). Angiotensin receptor blockers (ARB) can desensitize AT¹Rs by binding to an allosteric regulatory B-site, which overlaps with the AngII A/D binding site in the extracellular binding pocket of the receptor. ARBs shift the receptor conformation from A/D-mode to agonist-independent D*-mode, resulting in receptor internalization. Binding of ligands to the inverse agonist binding site (B-site) can promote (lock in) the D*-mode conformation of the receptor (desensitization) or disengage (lock out) the D-mode conformation (upsensitization, reduction of tolerance). Computer-aided docking (CAD) studies show that ARBs, particularly bisartan ACC519TT, bind with high affinity to several G protein-coupled receptors (GPCRs), including AT¹R, adrenergic (alpha 1 and 2), opioid (mu and delta), and muscarinic 3 receptors, suggesting that the electrostatic architecture of the B-site has been preserved across a broad spectrum of GPCRs. Consistent with CAD findings, ACC519TT significantly reduced dilation responses of mouse colon and small intestine to the opioid receptor agonist, oxycodone. Functional studies in rabbit iliac artery rings demonstrated the ability of lisinopril to significantly reduce AngII-induced contraction, comparable to candesartan. However, CAD studies show that lisinopril has a markedly lower affinity than candesartan for AT¹R, illustrating that the similar effect to AngII dose-response may be due to the time-dependent receptor internalization. For agonists, D-site versus A-site activity may provide insight regarding dependency potential (addiction ratio, D/A). Agonists cross-talk among different GPCRs creates the potential for a sophisticated interplay, possibly involving endogenous ligands not yet identified, with the notable exception of angiotensin antipeptide.

Abstract: Background: The rapid emergence of oral anticancer medications (OAMs) has increased demand for specialized Clinical Pharmacy Services (OAM CPS). Concurrently, Canadian cross-sectional data highlights severe undergraduate gaps, with fewer than 14% of community pharmacists reporting adequate undergraduate OAM training. We designed, implemented, and evaluated a pharmacist-led Oral Anticancer Medication Clinical Co-op Program (OAMCCP) to bridge this experiential education gap while safely and cost-effectively expanding institutional capacity. Methods: Launched in Fall 2022, the OAMCCP integrated one PharmD student per 16-week term into a multidisciplinary oncology specialty pharmacy. Trainees executed core ambulatory oncology clinical pharmacy key performance indicators (AOcpKPIs), including Best Possible Medication Histories (BPMH), drug-drug interaction (DDI) screenings, and proactive toxicity follow-up. Crucially, 100% of student tasks were verified by a licensed oncology pharmacist to maintain absolute patient safety. Impact was quantified via task logging over 15 weeks, standardized 10-point patient satisfaction surveys, and payroll expenditure comparisons. Results: Trainees completed 673 clinical tasks (56.1 tasks/week), contributing 19.2 hours of direct clinical support weekly—effectively adding +0.5 Full-Time Equivalent (FTE) to service capacity with zero safety compromises. Mean patient satisfaction was 9.6/10 (n = 29), with students independently managing inquiries in 96.5% of encounters. Financially, a 1.0 FTE student (\(44,700/year cost) captured clinical capacity valued at \)80,600/year (0.5 FTE pharmacist equivalence). Conclusion: The OAMCCP resolves experiential training gaps while presenting a safe, scalable, and financially viable human resource framework that expands oncology pharmacy services.

Abstract: Background. Therapeutic inertia — conventionally defined as the failure to initiate or intensify pharmacotherapy when clinical treatment targets are unmet and used in that under-titration sense throughout this review — is a pervasive and underappreciated source of preventable harm in ambulatory medicine. Despite decades of evidence-based guidelines and increasingly efficacious pharmacological agents, most patients with common chronic diseases remain on suboptimal medication doses, accruing avoidable morbidity, irreversible end-organ damage, and premature mortality. Objective. To characterize, in a unified cross-disease framework, the prevalence, clinical consequences, and economic burden of therapeutic inertia in pharmacologic dose titration across sixteen chronic conditions, and to summarize the case for new categories of intervention. Methods. Narrative review of peer-reviewed literature, clinical guidelines, and published health economic analyses. Searches were performed in PubMed and MEDLINE through April 2026 using condition-specific terms combined with “therapeutic inertia,” “clinical inertia,” “treatment intensification,” and “dose optimization.” Priority was given to systematic reviews, meta-analyses, prospective cohort studies, and large registry and database analyses since 2015, supplemented by seminal earlier studies and current guideline documents. U.S.-based sources were prioritized for epidemiologic and economic estimates. Results. Across sixteen conditions spanning cardiovascular, endocrine, obstructive airway, gastrointestinal, musculoskeletal, urologic, neurodegenerative, movement, sleep, and tobacco-dependence disorders, dose-optimization inertia or suboptimal pharmacotherapy maintenance is highly prevalent, ranging from approximately 55% (type 2 diabetes) to 99% (heart failure with reduced ejection fraction) across eligible patients or clinical encounters, among the nine conditions with a verifiable single-study point estimate (see Figure 1). Ten conditions produce life-threatening sequelae; six produce irreversibly debilitating functional and quality-of-life impairment without immediate life-threatening sequelae (osteoarthritis, benign prostatic hyperplasia, lower urinary tract symptoms/overactive bladder, essential tremor, restless leg syndrome, and Parkinson’s disease). Suboptimal titration is consistently associated with accelerated disease progression, irreversible end-organ damage inadequate symptom control, and preventable healthcare utilization. Aggregate annual U.S. direct and indirect costs for these conditions exceed $2.4 trillion, across the fifteen of sixteen conditions for which a comparable dollar-denominated estimate exists (essential tremor is excluded because the literature reports only relative cost multipliers). Existing technologies including provider education, EHR alerts, telehealth, standard remote patient monitoring, and digital therapeutics each operate within, rather than outside of, the structural constraints that produce inertia. Conclusions. Therapeutic inertia in pharmacologic dose titration is a systemic, cross-disease failure with shared structural determinants and no currently deployed solution capable of addressing it at population scale. The sixteen conditions reviewed collectively affect more than half of the adult U.S. population and account for majority of preventable mortality and disability in ambulatory care. The disparity between what evidence-based pharmacotherapy can achieve and what clinical systems reliably deliver represents one of the most consequential unmet needs in modern ambulatory medicine, and the populations bearing the greatest burden are those least served by current programs.

Abstract: Retinol and curcumin are bioactive compounds with promising dermatological applications; however, their poor aqueous solubility, instability, and limited bioavailability may restrict their therapeutic performance. This study aimed to develop and evaluate retinol-curcumin nanoemulsions (RCNEs) as a co-delivery system with antioxidant, anti-inflammatory, antibacterial, and in vitro safety potential. Curcumin and retinol were quantified using UV-visible spectrophotometry, and the nanoemulsions were prepared by mixing the aqueous and oily phases followed by sonication. The prepared formulations were evaluated for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, loading efficiency, and stability under different storage conditions. Antioxidant activity was determined using the DPPH radical scavenging assay, cytotoxicity was evaluated using the MTT assay on EaHY.926 endothelial cells, anti-inflammatory activity was assessed by measuring TNF-α inhibition, and antibacterial activity was tested against Staphylococcus aureus and Escherichia coli using the Kirby-Bauer well diffusion method. The optimized RCNE formulation showed an average particle size of 117 ± 0.1 nm, PDI of 0.138 ± 0.010, and zeta potential of −12.7 ± 0.2 mV. Encapsulation efficiencies were 77.0±1.1% for curcumin and 91.1±0.8% for retinol. RCNEs exhibited the strongest antioxidant activity, with an EC₅₀ of 56.04±1.95 µg/mL compared with 90.03±3.15 µg/mL for curcumin nanoemulsions and 227.3±8.4 µg/mL for retinol nanoemulsions (p≤0.05). The RCNE formulation also produced the highest TNF-α inhibitory activity, reducing TNF-α concentration to 76.5±5.2 pg/mL and achieving 86.2±1.8% inhibition, which was significantly higher than curcumin nanoemulsions (36.6±2.4%) and retinol nanoemulsions (39.1±2.1%) (p≤0.05). No marked cytotoxicity was observed within the tested concentration range. The formulation also demonstrated antibacterial activity against both tested bacterial strains, with larger inhibition zones against E. coli. These findings suggest that RCNEs may serve as a promising in vitro platform for co-delivering retinol and curcumin in topical pharmaceutical applications.

Abstract: Metabolic diseases, such as obesity, type 2 diabetes (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), emerge from chronic nutrient overload that progressively disrupts cellular homeostasis and precipitates persistent inflammatory remodeling. Two stress-adaptive programs sit at the center of such pathological transition: autophagy, the homeostatic engine responsible for lysosomal recycling and organelle quality control, and cellular senescence, a tissue repair system that becomes deleterious when persistent, driving dysfunction through stable growth arrest and senescence-associated secretory phenotype (SASP)-associated inflammatory remodeling. Emerging evidence identifies lysine acetylation as a nutrient-sensitive molecular rheostat that orchestrates the reciprocal regulation of these two processes across metabolic tissues. Because acetylation dynamics are governed by the availability of acetyl-CoA and the NAD⁺-dependent deacetylation capacity of sirtuins, metabolic stress reshapes the enzymatic balance between acetyltransferases (KATs, e.g., p300/CBP) and deacetylases. This shift triggers a “double blow” to cellular health; the simultaneous suppression of autophagic flux and the epigenetic stabilization of senescent state. This review synthesizes mechanistic evidence showing how acetylation inhibits autophagy at multiple checkpoints, ranging from the activity of core autophagy proteins to lysosomal biogenesis, while concurrently reinforcing senescence through chromatin hyperacetylation and the activation of non-histone effectors such as NF-κB, p53 and FOXO proteins. We place particular emphasis on the mTORC1-p300-SIRT1 axis as the primary integration hub coupling nutrient status to this dual regulation. Finally, we discuss tissue-specific manifestations in the liver, adipose tissue, and other metabolic organs and highlight emerging therapeutic strategies, such as KAT inhibition/sirtuin activation, aimed at restoring the acetylation rheostat to improve autophagic competence while restraining senescence-driven metabolic decline.

Abstract: Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug de-livery system (SNEDDS) using a Box–Behnken experimental design. Fifteen formulations were prepared and evaluated based on CQAs: cloud point, robustness to dilution, self-emulsification time, droplet size, zeta potential, and polydispersity index (PDI). The experimental responses were subjected to statistical analysis; robustness to dilution as the only response yielding a statistically valid and predictive model within the studied design space, which was used as the sole optimization criterion. The optimal formulation was evaluated and characterized according to previously established CQAs and subjected to physical/kinetic stability testing and stress testing over one month. The optimized formulation exhibited rapid self-emulsification, with a self-emulsification time of 37.02 s, a cloud point of 64.87 °C, and high robustness to dilution across different pH conditions and dilution volumes. Moreover, it exhibited a mean droplet size below 157.54 nm, a zeta potential of −15.43 ± 0.58 mV, and a PDI of 0.251, suggesting adequate colloidal stability and uniformity of the dispersed system. These physicochemical attributes support the potential of the developed system as a platform for further biopharmaceutical evaluation of ibuprofen oral delivery.

Abstract: This brief report evaluated June 2026 frontier generative artificial intelligence models on the Japanese National License Examination for Pharmacists. Four models (ChatGPT GPT-5.5, Gemini 3.5 Flash, Claude Opus 4.8, and Claude Fable 5) were tested using all 345 questions from the 107th examination, including image-based items in the original Japanese format. Overall accuracy counted refusals as incorrect, and conditional accuracy among answered questions was calculated for Fable 5. GPT-5.5, 3.5 Flash, and Opus 4.8 achieved near-saturation accuracies of 99.1%, 98.3%, and 96.8%, respectively. Fable 5 achieved 69.9% overall accuracy but 98.8% conditional accuracy among answered questions, refusing 101 questions (29.3%), especially in Biology (90.0%) and Pharmacology (72.5%). Frontier models showed near-saturation performance, but refusal-aware evaluation is necessary for pharmacy benchmarks.

Abstract: Background/Objectives: Traditionally classified as nutrients or micronutrients, vitamins can now be viewed as multi-functional excipients that have considerable potential within the context of pharmaceutical formulation science. Due to their physicochemical characteristics, antioxidant nature, and stabilizing action, vitamins are able to serve functions that go beyond their nutritional applications. These include but are not limited to solubility, increased permeation, controlled release, as well as synergistic stabilization and enhancement of the active ingredient(s). Results: The current work presents the synthesis of information available to date regarding the classification, mechanisms, and excipient properties of vitamins and their role in novel drug delivery systems development. In addition to the conventional classification into water-soluble and fat-soluble, some other classification criteria are used based on the chemical nature of vitamins. Water-soluble vitamins are mainly used to facilitate oxidation and pH adjustments whereas fat-soluble vitamins are mostly employed in lipid-based systems due to solubilizing and antioxidative effects. Conclusion: Vitamin-based mechanisms such as the surfactant effect of TPGS (vitamin E), oxidation and reduction reactions in vitamin C, or hydrotropy in niacinamide illustrate active involvement of vitamins in enhancing bioavailability and improving the formulation. Novel areas of application range from vitamin-functionalized nanocarriers to receptor-targeted ligands and incorporation into 3D-printed drug delivery platforms.

Abstract: Oral solid dosage forms are often preferred during drug product development as of-fering a flexible and cost-effective solution for patients, hence improving patient ad-herence. The efficacy of an orally administered drug is nonetheless limited by its bioa-vailability. pH modification is an effective solution to improve solubility of weak acidic or basic drugs via the formation of a microenvironmental pH. The objective of this study was to evaluate different formulation approaches to develop an immediate-release tablet or capsule containing fumaric acid as pH-modifier for enhancing the bioavaila-bility of a weakly basic API. The goal was to maximize the bioavailability of the drug with acceptable amounts of pH-modifier to ensure manufacturability and reduced capsule / tablet size for improved patient experience. In vitro data suggested that the over-encapsulated tablet prototype led to improved bioavailability even in highly buff-ered achlorhydric conditions and was therefore the most robust formulation toward elevated gastric pH. However, in low buffered achlorhydric conditions the monolayer tablet with acid exhibited similar dissolution rate and prototypes with less close contact between the API and the organic acid also demonstrated improved dissolution rates. These results suggested that the acidic microenvironment may not require such a high degree of contact between the API and the pH-modifier. The outcomes of this study, and consequently the bio-relevance of tested media, will have to be further evaluated in vivo.

Abstract: Wound healing is a complex biological process involving inflammation, hemostasis, and tissue regeneration, and its impairment may delay recovery and lead to clinical com-plications. Medicinal plants have long been used in traditional medicine to support wound repair and control bleeding. Among these, Symphytum officinale L. (comfrey) is widely used in European traditional medicine for the treatment of wounds, fractures, and soft tissue injuries. However, the pharmacological basis of these effects and the contribution of different plant organs remain insufficiently understood. The aim of this study was to characterize the phytochemical composition of extracts obtained from different organs of S. officinale and to evaluate their hemostatic and wound-healing activities in vivo, in order to identify the most active plant parts. Extracts from the roots, leaves, and flowers of S. officinale were prepared using solvents of different polarity. Phytochemical composition was analyzed by spectrophotometric assays and UPLC–MS/MS. Hemostatic and wound-healing activities were evaluated in vivo in rats, and cytological analysis of wound exudate was performed. Distinct organ-specific differences in phytochemical composition were observed, with leaf and flower extracts richer in phenolic compounds and amino acids, while root extracts contained higher levels of pyrrolizidine alkaloids. Leaf (S7) and flower (S13) extracts showed the strongest biological activity. S13 accelerated wound healing, achieving complete closure by day 10, while S7 exhibited the most pronounced hemostatic effect. Cytological analysis indicated reduced inflammation and enhanced fibroblast activity. The findings support the traditional use of S. officinale in wound treatment and highlight the importance of organ-specific phytochemical composition. Aerial parts showed strong wound-healing and hemostatic effects, suggesting their relevance alongside the traditionally used root and indicating a multi-component basis for its activity.

Abstract: In the present study, rapid, robust and reproducible reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for simultaneous determination of avobenzone and octocrylene in bulk and sunscreen formulation. The separation was done at a flow rate of 1.0 mL/min on a Symmetry C18 (4.6 × 250 mm, 5 μm) column at 5% water and 95% methanol as mobile phase and at the detection wavelength of 256 nm. Under the optimal chromatographic conditions, octocrylene and avobenzone were eluted at 4.0 and 6.6 min, respectively, with good peak symmetry and resolution. The developed method was validated as per the criteria mentioned in ICH Q2 (R1) such as System suitability, Specificity, Linearity, Precision, Accuracy, Sensitivity, Robustness, Ruggedness and Solution stability. The method showed a good linear range of 10–50 μg/mL with correlation coefficient of 0.9979 for octocrylene and 0.9976 for avobenzone. The %RSD for the precision studies were < 2%, which represents good intermediate and repeatability precision. The percentage recoveries were within the acceptable limits of the analysis and acceptable accuracy was achieved in the recovery studies. An equivalent method was also proved to be robust for intentional changes of the chromatograph conditions. Furthermore, the validated method could be used with nanosponge-loaded sunscreen lotion formulations and there was no interference of the excipients. The proposed RP-HPLC method is easy, economical, sensitive and can be applied in the routine quality control analysis of avobenzone and octocrylene in pharmaceutical and cosmetic formulations.

Abstract: This study investigates the synergistic therapeutic potential of Rivastigmine (RVG) and Epigallocatechin (EGC) in Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by neuroinflammation, oxidative stress, and dysregulated signaling pathways. Conventional therapies primarily provide symptomatic relief and target limited pathways, highlighting the need for multi-target strategies with improved efficacy and safety. An integrated in-silico approach combining pharmacokinetic evaluation, network pharmacology, molecular docking, and molecular dynamics simulations is used to determine the synergistic potential of RVG and EGC. Pharmacokinetic analysis indicates favorable drug-likeness and acceptable ADME/Tox profiles for both compounds. Network pharmacology identified 146 overlapping targets associated with AD, highlighting key hub genes including NFKB1, MAPK1, STAT1, PRKACA, GRB2, LYN, and PTPN11 are involved in neuroinflammation, synaptic signaling, and neuronal survival. Functional enrichment analysis indicated significant involvement of MAPK/ERK signaling and immune-regulatory pathways. Importantly, the PD-1/PD-L1 signaling pathway is identified as a novel mechanistic connecting neuroimmune modulation with intracellular kinase-driven neurodegeneration. Molecular docking studies showed strong binding affinities of RVG and EGC toward key AD-related targets, particularly MAPK1, supported by stable hydrogen bonding and interaction profiles. Molecular dynamics simulations confirmed stable protein-ligand interactions, with EGC contributing structural stability and RVG exhibiting adaptive flexibility within the binding pocket. These results suggest that the RVG-EGC combination exhibits synergistic potential by simultaneously modulating neuroinflammatory, oxidative stress, and kinase-mediated signaling pathways. The integration of PD-1/PD-L1 and MAPK/ERK signaling provides a novel mechanistic pathway for multi-target therapeutic intervention in AD.

Abstract: Plant-derived compounds exhibit well-documented osteogenic and anti-resorptive activities; however, their translation into consistent skeletal benefits remains limited. This review proposes a transformation-state–dependent framework in which the efficacy of plant-based interventions is interpreted through the exposure architectures they generate rather than solely through intrinsic molecular activity. By integrating plant matrix organization, gastrointestinal processing, microbial biotransformation, and formulation-driven pharmacokinetics with the temporal dynamics of bone remodeling, the review addresses a critical gap in current literature, which largely evaluates phytochemicals independent of their delivery context. Across a continuum ranging from intact plant matrices to isolated compounds and advanced delivery systems, distinct pharmacokinetic regimes emerge, characterized by differences in release kinetics, metabolic transformation, systemic persistence, and target-site exposure. Evidence indicates that sustained, metabolite-mediated exposure profiles are more compatible with the prolonged, cumulative nature of bone remodeling, whereas transient exposure often limits efficacy despite mechanistic activity. Formulation strategies, including phospholipid complexes, bioenhancers, and nano- or vesicle-based systems, can partially overcome these limitations by modulating exposure behavior. By reframing plant-based interventions as dynamic exposure systems, this framework provides a unifying basis for interpreting variability across studies and offers a rational foundation for designing strategies that align pharmacokinetic behavior with skeletal biology, thereby improving translational potential.

Abstract: Antibody–drug conjugates (ADCs) are a pivotal technology for precision cancer therapy, harnessing the synergistic effects of antibody targeting and toxin delivery. However, traditional ADCs encounter limitations in efficacy that stem from tumor resistance, heterogeneity, and intense target competition. Dual-payload ADCs (DP-ADCs) represent a promising solution to these challenges, as they leverage dual mechanisms of action that mitigate acquired drug resistance and enhance adaptability to tumor heterogeneity. The complex structure of DP-ADCs presents substantial quality control hurdles. In this manuscript, we review the current payload selection and conjugation strategies of DP-ADCs and examine recent advances in quality control research. Specifically, we analyze the analytical challenges related to the quantification of free toxins, the determination of the total antibody content, and the characterization of the drug-to-antibody ratio and its distribution. Ultimately, the aim of this work is to provide valuable guidance for future DP-ADC quality control analyses to facilitate their clinical translation and application.

Abstract: Background/Objectives: Dolutegravir is an integrase strand transfer inhibitor widely used in HIV therapy due to its high resistance barrier and favourable safety profile. As pharmacopoeial coverage continues to evolve and local formulation efforts increase, relia-ble analytical methods are required to ensure drug quality, safety, and efficacy. This study aimed to develop and validate two simple, sensitive, and cost-effective high-performance liquid chromatography with UV detection (HPLC-UV) methods for quantifying dolute-gravir in bulk form and human plasma. Methods: Reverse-phase HPLC methods were developed and validated according to ICH Q2(R2) guidelines. Hydrochlorothiazide and carbamazepine were used as internal standards for bulk and plasma analysis, respective-ly. Chromatographic separation was achieved on C18 columns. Key validation parameters included linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), robustness, and system suitability. Plasma samples were prepared using liquid–liquid extraction with diethyl ether. Results: The bulk method showed excellent linearity over 0.5–100 µg/mL with an R2 of 0.9997, while the plasma method was linear over 0.8–10 µg/mL with an R2 of 0.9956. Accuracy ranged from 95.2% to 104.4% for bulk and showed acceptable recoveries for plasma samples. Precision was satisfactory with %RSD values below 6% across all methods. LOD and LOQ were 0.42 µg/mL and 1.26 µg/mL for bulk analysis, and 0.55 µg/ml and 1.68 µg/ml, for plasma analysis respectively. Robustness and system suitability tests confirmed method reliability. Conclusions: The developed HPLC-UV methods are simple, reproducible, and suitable for routine quality control of dolutegravir in pharmaceutical formulations and for its quantification in human plasma for pharmacokinetic applications.

Abstract: Rational use of medicines (RUM) is a cornerstone of safe, effective, and affordable health care. In Nepal, irrational medicine use-particularly of antibiotics-remains widespread, driven by self-medication, over-the-counter (OTC) sales without prescription, inappropriate prescribing practices, weak regulatory enforcement, and commercial influences. These practices contribute directly to the growing burden of antimicrobial resistance, increased adverse drug reactions (ADR), and avoidable economic costs for households and the health system. This perspective article synthesizes recent evidence from knowledge, attitude, and practice (KAP) studies, national policy experiences, and global trends from the past five years to examine the magnitude and drivers of irrational medicine use in Nepal. Ensuring RUM is a shared responsibility involving individuals, communities, health professionals, regulators, policymakers, pharmaceutical industries, and the media. Strengthening RUM in Nepal requires coordinated regulatory enforcement, antimicrobial stewardship, and community-level behavior change.

Abstract: Background: Good Pharmacy Practice (GPP) provides a globally recognized framework to promote the safe, effective, and rational use of medicines while strengthening the role of pharmacists in patient-centered health care. To enhance awareness and practical understanding of GPP principles in the local context, a one-day workshop titled “GPP: Strengthening the Role of Pharmacists in Health Care Delivery” was conducted. Methods: The workshop was facilitated by subject experts and faculty members and included focused presentations and interactive discussions addressing key components of GPP, such as rational use of medicines, medication counseling, professional ethics, and the evolving responsibilities of pharmacists. Particular emphasis was placed on the current status, challenges, and opportunities for GPP implementation in Nepal in comparison with international standards. Participant feedback was collected at the end of the program. Results: Participants reported a high level of satisfaction with the workshop, highlighting the relevance and clarity of the content as well as its perceived professional and career-related benefits. Interactive discussions enabled participants to identify context-specific challenges and opportunities in pharmacy practice in Nepal. Minor logistical limitations, including sound system and internet connectivity issues, were noted but did not significantly affect overall engagement. Conclusion: The workshop underscored the importance of continuous professional development initiatives to strengthen the implementation of GPP and enhance pharmacists’ contributions to health care delivery. Conducting similar capacity-building programs, particularly in remote and underserved regions, may support the promotion of standardized pharmacy practice and contribute to improved health care outcomes in Nepal.

Abstract: Background: Effective pharmacy regulation is a cornerstone of patient safety and rational medicine use. In Nepal, despite the existence of regulatory frameworks such as the Drug Act 2035 and policies restricting non-prescription sales of antibiotics, enforcement is weak and inconsistent, leading to widespread regulatory failure in community pharmacies. Problem: Multiple studies have documented widespread dispensing of antibiotics without valid prescriptions in community pharmacies across Nepal, with non-pharmacist staff frequently engaging in these practices. Analysis: Policy and practice gaps in Nepal’s pharmacy sector reflects systemic issues including insufficient regulatory capacity, workforce shortages of qualified pharmacists, market-driven dispensing behaviors, and low public awareness of rational medicine use. These structural barriers continue unsafe pharmaceutical care and weaken pharmacovigilance systems. Policy Implications: Strengthening enforcement must be reframed as a health systems and patient safety priority rather than a narrow regulatory task. A multi-pronged strategy including mandatory qualified pharmacist presence, enhanced inspection and compliance monitoring, integration of community pharmacies into national antimicrobial stewardship programs, and public awareness campaigns is urgently needed. Conclusion: Weak enforcement of pharmacy regulation in Nepal constitutes a significant but under-recognized threat to patient safety and antimicrobial stewardship. Translating existing policies into practice through systemic reforms can reduce medication-related harm and preserve antibiotic effectiveness.