Medicine and Pharmacology

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.

Abstract: Background/Objectives: Oritavancin therapy for complex infections remains challenging due to the lack of well-established dosing regimens. The objective of this work was to apply PK/PD modeling and Monte Carlo simulation considering different PK/PD targets to identify multiple dosing regimens that may ensure effective concentrations of oritavancin for the treatment of long-term infections. Methods: Plasma concentration–time profiles were simulated for different regimens (single dose of 1200 mg, 1200 mg followed by 800 mg every 7 days, 1200 mg followed by 800 mg every 10 days, 1200 mg q7d, 1200 mg q10d, 1200 mg every 14 days, 1200 mg every 21 days, and 1200 mg followed by 1200 mg on day 8, then 1200 mg q14d), and the probability of target attainment (PTA), indicative of treatment success, was estimated. Results: All dosing regimens provided probabilities of target attainment of 100% up to MICs of 0.5 mg/L when AUC_0-24/MIC and C_max/MIC were applied. Considering AUC_0-72/MIC, the regimens would be adequate up to MIC of 0.125 mg/L. For fC_min > MIC, all except 1200 mg q21d resulted adequate for MIC of 0.125 mg/L, and 1200 mg day 1 + 800 mg q7d, and 1200 mg q10d may be useful to treat infections due to bacteria with MIC of 0.25 mg/L. Conclusions: More studies involving patients with complex infections are needed to better stablish the relationships among plasma concentrations, MIC values, and clinical outcomes. fC_min > MIC should be investigated as a potential PK/PD target for the treatment of these infections with oritavancin.

Abstract: Topical semisolid formulations based on biopolymers and plant-derived components have attracted increasing attention for wound healing applications. However, their physicochemical stability and biological performance are strongly influenced by formulation composition and structural organization, which necessitates further systematic investigation. The aim of this study was to develop and optimize oil-in-water cream formulations based on biopolymer systems containing chitosan, xanthan gum, and plant extracts of Hypericum perforatum and Calendula officinalis. The formulations were prepared using a conventional emulsification method and evaluated in terms of pH, viscosity, rheological behavior, microbiological purity, and antimicrobial activity. Initial systems exhibited low viscosity and insufficient structural stability, which were improved by the incorporation of xanthan gum as a stabilizer. The optimized formulations demonstrated non-Newtonian shear-thinning behavior and pH values of 6.35 ± 0.08, indicating suitability for topical application. Formulations containing plant extracts did not exhibit antimicrobial activity against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027. In contrast, the formulation containing naringin demonstrated selective bactericidal activity against Staphylococcus aureus up to a dilution of 1:16, with no effect observed against Pseudomonas aeruginosa. Overall, the developed systems showed appropriate physicochemical and rheological properties for dermal application. The study demonstrates that physicochemical optimization does not necessarily correlate with antimicrobial performance, highlighting the importance of formulation composition.

Abstract: This study used chemometric models to measure caffeine (CAF), aspirin (ASP), and paracetamol (PAR) in the presence of three hazardous impurities: salicylic acid (SAL), P-nitrophenol (PNP), and P-chloroacetanilide (PCA). A molecular docking study was used to examine how impurities might inhibit cyclooxygenase-2, highlighting the importance of controlling their levels if present in the dosage form. Four sustainable chemometric models: principal component regression, multivariate curve resolution-alternating least squares, artificial neural networks, and partial least squares, were developed. The quantitative analytical performance of all proposed models was evaluated using the per cent recovery, standard error of prediction, and root mean square error of prediction. The developed models covered the concentration ranges (in µg/mL) of PNP (2.00-6.00), PCA (0.50-0.90), SAL (6.00-14.00), ASP (6.00-14.00), CAF (3.00-19.00), and PAR (2.00-10.00). These models effectively addressed collinearity and spectral overlaps. Seven innovative tools, including the Carbon Footprint Reduction Index, Click Analytical Chemistry Index, Multicolour assessment tool, Analytical Green Star Area, spider chart, green solvent selection tool, and Modified Green Analytical Procedure, were used to calculate the sustainability and whiteness of the developed models.

Abstract: Dissolving microneedles (DMN) could be considered as a promising platform for transdermal delivery of naltrexone hydrochloride (NTX), providing a minimally inva-sive alternative to conventional administration routes. In the present study, DMN patches with an advanced design were developed via a two-step micromoulding tech-nique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and poly-vinyl alcohol (PVA) blend microneedle tips, combined with a drug-loaded backing layer based on PVP and the thermoresponsive polymer Poloxamer 407. The influence of polymer concentration into DMN tips and backing layer composition on morpholo-gy, mechanical properties, drug release and permeation was evaluated. Mechanical studies as well as SEM observation revealed that intermediate polymer concentration (formulation MN-20%/2:1), used for DMN tips preparation, provided optimal mi-croneedle geometry, superior structural integrity and penetration efficiency. Incorpo-ration of NTX into backing layer allowed high and uniform drug loading. In vitro per-meation studies demonstrated significantly enhanced NTX delivery from DMN sys-tems compared to simple matrix patches, with the thermoresponsive backing layer contributing to controlled drug release. These findings highlight the importance of polymer composition in DMN design and demonstrate the potential of the developed systems as an effective platform for transdermal delivery of NTX.

Abstract: Diabetic neuropathy (DN) is a progressive nerve disorder caused by diabetes, characterized by chronic high blood sugar that leads to nerve inflammation and damage, resulting in pain, numbness, and loss of sensation. Current synthetic therapies often produce adverse effects such as hypoglycaemia, weight fluctuations, and organ toxicity, which hinder patient compliance and increase interest in herbal alternatives. This study evaluated a novel polyherbal extract (PHE) against diabetic neuropathy induced by a high-fat diet and streptozotocin (HFD-STZ) in rats. The PHE was prepared in a 2:2:1 composition ratio by decoction method. In the rat model, subjects received different doses of PHE (100, 200, and 400 mg/kg p.o) or gabapentin (300 mg/kg p.o) for 45 days. At the highest dose of 400 mg/kg, PHE significantly alleviated neuropathic symptoms, as shown by reduced mechanical allodynia and thermal hyperalgesia. It also improved glycemic control, normalized lipid profiles, and decreased oxidative stress markers by lowering lipid peroxidation while increasing levels of glutathione, superoxide dismutase, and catalase. Additionally, PHE enhanced gastric emptying time and exhibited neuroprotective effects by preserving the architecture of the sciatic nerve. In MIN6 β-cells, PHE maintained cell viability and stimulated glucose-dependent insulin secretion, highlighting its therapeutic potential for managing diabetic neuropathy.

Abstract: Phosphodiesterase-1 (PDE1) represents an attractive target for the treatment of idiopathic pulmonary fibrosis (IPF). However, the limited chemical diversity of current PDE1 inhibitors has hindered the development of potential anti-IPF drugs, primarily due to an ambiguous understanding of interactions between inhibitors and PDE1. Herein, we report an integrated virtual screening strategy containing pharmacophore modeling, molecular docking, and molecular dynamics simulations, which markedly accelerated the discovery of novel PDE1 inhibitors. Enzymatic assays identified eleven active compounds with moderate inhibition from twenty-six purchased candidates, encompassing nine distinct scaffold types. Notably, 6484-0008 and 6484-0032 exhibited more than 50% inhibition at a concentration of 1 μM. Hydrogen bonding analysis and residue-based energy decompositions revealed key recognition mechanisms involving crucial residues Gln421, His373, and Phe424, as well as the unique Thr271 in the flexible H-loop region, providing insights for the rational design of inhibitors with enhanced potency.

Abstract:

Objective: To compare the efficacy, safety, weight reduction and treatment adherence of oral versus subcutaneous semaglutide in adults with uncontrolled T2DM and obesity. Methods: A multicenter retrospective cohort study was conducted between January 2023 and January 2024. Adult patients (≥18 years) with T2DM (HbA1c ≥ 7%) and obesity (BMI ≥ 30) who received either oral or subcutaneous semaglutide were included. Demographic, clinical, and biochemical variables including body weight, BMI, HbA1c, side effects, and adherence were extracted from electronic medical records. Adverse effects were categorized by severity. Comparative analyses between groups used Chi-square and Mann Whitney U tests, with p<0.05 considered statistically significant. Results: A total of 208 patients were included: 89 on oral semaglutide and 119 on subcutaneous semaglutide. Baseline demographics, including gender, age, and physical activity, were comparable between groups (all p>0.05). The severity of adverse effects predominantly gastrointestinal symptoms such as nausea, vomiting, constipation, and diarrhea did not differ significantly between groups (p=0.994). However, dizziness was significantly more frequent in the subcutaneous group (p = 0.04). Adherence was markedly higher with oral semaglutide (p<0.05), with cost identified as the primary barrier among oral users, while subcutaneous users more frequently cited side effects, forgetfulness, and limited weight loss. Weight reduction was comparable at 3 months (p=0.23), but significantly greater with oral semaglutide at 6, 9, and 12 months (all p<0.01). Conversely, HbA1c reduction favored subcutaneous semaglutide at 3 and 6 months (p=0.03 and 0.02), although baseline glycemic control was similar. Conclusions: This study demonstrates that while subcutaneous semaglutide may provide a faster early HbA1c decline, oral semaglutide offers superior long-term weight reduction and significantly better adherence, likely attributable to easier administration. Both formulations exhibited comparable safety profiles.

Abstract: This study addresses the challenge of transdermal delivery of cyanocobalamin (vitamin B12), a hydrophilic macromolecule with low permeability, by developing biodegradable polymeric microneedle (MN) patches. Conventional methods often suffer from poor bioavailability, but microneedle technology can bypass the stratum corneum barrier, thereby improving drug delivery efficiency. We fabricated MN patches using hydroxypropyl methylcellulose (HPMC K4M), polyvinylpyrrolidone (PVP K30), and polyethylene glycol (PG 4000) through a mold-casting technique, followed by characterization of drug content, release kinetics, and mechanical properties. The optimized formulation (M18) demonstrated high drug content (95.2%) and sustained release (96.4% at 24 hours), while FTIR confirmed no drug-polymer interactions, ensuring stability. Moreover, SEM revealed uniform needle dimensions (867.25 ± 7.35 µm in height), and texture analyzer tests validated robust mechanical integrity. The patches exhibited low moisture content (3.42%) and high folding durability (&gt;200 folds), indicating suitability for storage and application. These results highlight the potential of polymeric MN patches as a non-invasive, efficient alternative for transdermal delivery of hydrophilic macromolecules. The study contributes to the field by providing a scalable, stable, and high-performance delivery system, which could significantly impact treatments for vitamin B12 deficiency and similar therapeutic needs.

Abstract: Background:Advances in oncology have led to the development of novel targeted therapies with demonstrated efficacy in clinical trials; however, their real-world economic impact prior to and after market introduction remains insufficiently characterized [1,2]. Cancer-related healthcare costs vary significantly depending on disease stage, time since diagnosis, tumor type, and therapeutic approach[3–6], making inter-hospital comparisons challenging due to heterogeneity in patient populations and information systems [7]. Therefore, integrating cost analysis with clinically meaningful patient stratification is essential to improve resource allocation and outcome evaluation[8–12]. Methods: A multicentre working group comprising four tertiary hospitals in Madrid (Spain) was established to develop and validate a novel classification system for adult oncohematological patients. A standardized methodology was designed to stratify patients into homogeneous groups (PATONCO categories) based on tumor location, therapeutic objective, and clinically relevant biomarkers. A cost indicator was defined as the average cost per patient per month for each PATONCO category. Data were extracted from pharmacy dispensing systems and analyzed using descriptive and inferential statistics, including Kruskal–Wallis and post hoc Dunn tests. Results: A total of 3,659 patients were included (3,168 oncology; 491 hematology), distributed across 62 programmes (54 oncology; 8 hematology). The PATONCOS tool enabled the identification and validation of a cost indicator (average cost/patient/month per category), allowing inter-hospital comparison. Significant differences in costs were observed across most high-prevalence categories, reflecting variability in therapeutic strategies and adoption of innovative treatments. The model demonstrated its capacity to detect intra-group homogeneity and inter-group variability, improving the identification of high-cost patient subgroups and supporting benchmarking across centres. Conclusions: The PATONCOS tool provides a novel, clinically oriented stratification methodology that integrates pharmacotherapy, biomarkers, and disease stage with economic evaluation. This approach enables more accurate comparisons of oncology treatment costs between institutions and supports data-driven decision-making in resource allocation. Its implementation may contribute to more sustainable healthcare systems by aligning clinical practice with economic outcomes.