Medicine and Pharmacology

Abstract: Lipid-based nanocarriers, especially vesicular systems such as liposomes, have gained an important place in the development of nanomedicines due to their biocompatibility and ability to simultaneously encapsulate hydrophilic and lipophilic cargoes. However, component selection alone does not determine the performance and safety of these formulations; the manufacturing process, in particular the solvent system, has a significant impact. In this article, the selection of solvents and co-solvents for the synthesis of lipid nanocarriers is explained, demonstrating how the type of solvent and the conditions of mixing can affect key attributes like particle size, polydispersity index, surface charge, and encapsulation efficiency. In parallel, residual solvents represent a quality and safety concern and form part of the control strategy within chemistry, manufacturing, and controls (CMC). Regulatory requirements on solvent classification and permissible residual limits based on permitted daily exposure (PDE), as well as their implications for designing quality-control strategies, are also reviewed. Finally, by comparing conventional and advanced methods, the opportunities and challenges of low-solvent and solvent-free approaches are discussed as pathways aligned with a risk-based perspective and scalable manufacturing.

Abstract: Background/Objectives: Long-term drug-utilisation surveillance can identify changes in pharmaceutical distribution and expenditure. We examined recorded systemic antiviral utilisation, therapeutic composition and expenditure across three distribution channels in Kazakhstan during 2013–2025. Methods: Quarterly IQVIA records were analysed using World Health Organization Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. Of 289 source product presentations, 273 met the eligibility criteria and 271 had an applicable defined daily dose (DDD). Utilisation was expressed as DDDs per 1,000 inhabitants per day (DID). Annual percentage changes (APCs) were estimated using log-linear models with robust covariance and sensitivity analyses. Recorded wholesale-sales values were adjusted to 2025 Kazakhstani tenge (KZT) using the official pharmaceutical consumer price index (CPI). Results: DDD-eligible presentations accounted for 279.66 million DDDs. Utilisation increased from 1.361 to 4.569 DID (APC 12.2%; 95% confidence interval 9.8–14.8). Retail commercial distribution represented 64.3% of the 2025 DDD-based total. Reimbursed outpatient utilisation increased fastest from a low, variable baseline. Total CPI-adjusted expenditure increased from KZT 12.983 billion to 30.147 billion. Within the matched DDD-eligible subset, expenditure per DDD decreased by 49.2%, from KZT 1,535 to 780. Conclusions: The findings identify retail distribution and therapeutic composition as priorities for surveillance and prescribing audits. Recorded sales do not establish treatment coverage, clinical appropriateness or procurement efficiency.

Abstract: An HPMC/TPGS-based amorphous solid dispersion (ASD) of Apixaban (APX) was developed to improve supersaturation maintenance, colloidal dispersion, and oral exposure. Screening studies showed that HPMC was the most suitable polymer for maintaining APX supersaturation, while TPGS provided the greatest solubilizing effect among the surfactants tested. The HPMC and TPGS ratios were subsequently optimized using a central composite design based on five responses: supersaturation solubility, kinetic solubility at 30 min, kinetic solubility area under the curve (AUC), particle size, and polydispersity index (PDI). The selected formulation contained HPMC and TPGS at ratios of 3.93 and 0.85 relative to APX, respectively, with a composite desirability of 0.8491. Validation of the optimized ASD yielded a supersaturation solubility of 112.1 ± 2.2 μg/mL, a 30-min kinetic solubility of 360.1 ± 4.4 μg/mL, a kinetic solubility AUC of 118545.6 ± 1053.6 μg·min/mL, a particle size of 203.4 ± 17.3 nm, and a PDI of 0.246 ± 0.018. PXRD and DSC analyses showed loss of APX crystallinity, while morphological observations by SEM and TEM, together with DLS measurements after aqueous dispersion, supported the formation of nanosized colloidal particles. The optimized ASD also maintained higher kinetic solubility in fasted-state simulated intestinal fluid (FaSSIF, pH 6.5) than crystalline and amorphous APX. For pharmacokinetic evaluation, the formulations were orally administered to rats, and plasma APX concentrations were measured. Compared with crystalline APX powder, the optimized ASD increased Cmax, AUC0–24, and AUC0–inf by 2.46-, 3.04-, and 2.80-fold, respectively. Overall, the HPMC/TPGS-based ASD improved both the dissolution-related performance and systemic exposure of APX.

Abstract: Background/Objectives: The same medicinal plant can interact differently with other plants in their combinations, with expectations of higher efficacy and improved safety. Kan Jang® is a fixed combination of standardized extracts of Herba Andrographidis and Radix Eleutherococci used to treat upper respiratory tract infections (URTIs), influenza, sinusitis, pharyngotonsillitis, and, more recently, mild COVID-19. However, recent pharmacovigilance signals indicate that Andrographis paniculata leaf extracts in combination with Radix Echinacea-containing preparations can unexpectedly cause serious allergic reactions, including anaphylaxis. The Australian Therapeutic Goods Administration (TGA) warning to exclude Andrographis from the list of low-risk products assumes its product-specific pharmacological profile remains the same when combined with other plant extracts. However, 9 clinical trials of Kang Jang involving 1544 patients with URTIs, along with post-marketing reports from 1989 to the present, show it to be harmless despite containing Andrographis. This review aims to explain why Kang Jang may be less harmful than other Andrographis-containing products. Methods: We conducted a mixed-methods narrative review using evidence from clinical trials, systematic reviews, transcriptomic investigations, network-pharmacology analyses, mechanistic studies, toxicology reports, and pharmacovigilance assessments, retrieving literature published between 1980 and 2026 from major scientific databases and regulatory sources. Results: Several factors explain Kan Jang's superior safety compared with other Andrographis-containing preparations. Kan Jang fundamentally differs by: (i) its chemical composition (presence of Eleutherococcus extract and lack of possible impurities forming as a result of other extractive solvents), (ii) pharmaceutical characteristics (different raw materials - leaves vs. aerial parts; solvents - 70% vs. methanol and water), (iii) clinical and postmarketing safety, and (iv) synergistic and antagonistic interactions of components of Kan Jang (Andrographis and Eleuthero-coccus) in the cells of the human body. Transcriptomic studies demonstrated that the combination produces a distinct gene-expression profile characterized by both synergistic and antagonistic interactions, including regulation of genes not affected by either constituent alone. Mechanistic analyses identified effects on interferon signaling, immune regulation, inflammatory pathways, KEAP1–Nrf2-mediated oxidative stress responses, cytoprotective mechanisms, and host-defense networks. Across clinical studies and post-marketing surveillance, Kan Jang exhibited a favorable safety profile with predominantly mild adverse events and no validated pharmacovigilance signal for serious hypersensitivity reactions. Conclusions: Kan Jang has a favorable observed clinical and post-marketing safety profile, in contrast to a validated pharmacovigilance signal for anaphylaxis associated with some other polyherbal products, including Andrographis and Radix Echinacea extracts. Preclinical transcriptomic and mechanistic findings provide a plausible biological basis for differences between the Kan Jang combination and Andrographis monotherapy. Clinical studies indicate that Kan Jang improves symptoms and recovery in URTIs, influenza, and mild COVID-19, with reported benefits including accelerated symptom resolution and improved physical functioning.

Abstract: (1) Background: Low molecular weight heparins have shown to significantly reduce the incidence of venous thromboembolism in at risk postpartum women. In 2021, the VTE guideline at the study hospital was updated to replace earlier versions and align with national standards. One of the changes in practice was extending thromboprophylaxis with enoxaparin to 10 days after emergency or non-elective caesarean sections. This study aims to evaluate postnatal patient experiences, educational adequacy, and adherence with enoxaparin administration after hospital discharge following the practice change. (2) Methods: A telephone survey was conducted with 30 postpartum patients who were prescribed enoxaparin upon discharge from the hospital. The survey included questions regarding their adherence, administration, disposal methods, and confidence in self-administration. The data was analysed to identify common themes and areas needing improvement. (3) Results: The adherence rate among patients was 23/30, 76.7% of patients used all provided enoxaparin injections. Non-adherence was primarily due to pain/discomfort and lack of confidence. Less than half of all patients reported self-administration, with 18/30, 60.0% requiring administration by their partner/family member. Fear of needles and discomfort were the reported barriers to self-administration. All patients reported receiving education, with 6/30, 20.0% of patients felt their training was inadequate. Proper disposal of used injections was reported by 27/30, 90.0% of patients. (4) Conclusion: The study highlights the importance of comprehensive and multidisciplinary education for postnatal patients prescribed enoxaparin. Standardisation of the education given to patients, early initiation of self-administration, and supportive environments may help to improve adherence and patient confidence.

Abstract: Background/Objectives: Curcumin has potential hepatoprotective effects in non-alcoholic fatty liver disease (NAFLD), but its poor aqueous solubility limits formulation development. This study aimed to prepare a curcumin solid dispersion (CSD) using polyvinylpyrrolidone K30 (PVP K30) and phosphatidylcholine to evaluate its physicochemical properties and hepatoprotective effects. Methods: CSD was prepared by solvent evaporation at a curcumin/phosphatidylcholine/PVP K30 weight ratio of 1:2:3. X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy were used for characterization. Apparent solubility and in vitro dissolution were assessed in buffers at pH 1.2, 4.5, and 6.8. Raw curcumin and a corresponding physical mixture were used as comparators. Hepatoprotective effects were investigated in a high-fat diet/lipopolysaccharide-induced experimental NAFLD model using serum biochemical markers, hepatic inflammatory cytokines, and liver histology. The animal study compared oral CSD at curcumin-equivalent doses of 50 and 100 mg/kg/day with unformulated curcumin at 200 mg/kg/day. Results: The dispersion showed diffraction and thermal profiles consistent with amorphization of curcumin. Apparent solubility reached 184.2, 232.6, and 292.1 µg/mL at pH 1.2, 4.5, and 6.8, respectively. At pH 1.2, the reported 90 min cumulative dissolution increased from 8.8% for unformulated curcumin to 87.9% for CSD. CSD treatment was associated with lower serum ALT and ALP levels, reduced hepatic lipid accumulation, and decreased hepatic TNF-α, IL-6, and IL-1β levels. Conclusions: The PVP K30/phosphatidylcholine-based solid dispersion improved curcumin's apparent solubility and dissolution and showed hepatoprotective effects in an experimental NAFLD model. These findings support further evaluation of this formulation approach.

Abstract: This article provides a comprehensive overview of recent advances in liposomal nanoformulations encapsulating whole-plant extracts for topical skin applications, with a focus on research published between 2016 and 2026. Literature searches were conducted using the Web of Science, Scopus and PubMed databases. The evolution from conventional liposomes to advanced nanovesicles (ethosomes, transfersomes, transethosomes, propylene glycol- and glycerol-enriched liposomes, and (bio)polymer-coated nanovesicles) is analyzed alongside their integration into hybrid liposome-in-vehicle delivery systems. Liposome preparation methods, bilayer constituents, and semisolid vehicles used to increase viscosity of liquid liposomal dispersions were evaluated and discussed with respect to their physicochemical properties as well as the botanical, phytochemical and biological activity profiles and skin-related effects of the plant-extract-loaded liposomal nanocarriers. Encapsulation into liposomes was found to significantly enhance the stability of botanical extracts, their cutaneous deposition, as well as therapeutic efficacy and dermocosmetic potential. Reported biological effects were categorized according to their pharmacological activities, such as antioxidant, anti-melanogenic, anti-inflammatory, antimicrobial, cytotoxic, wound-healing, and anti-aging activities. In response to the growing demand for clean beauty and plant-based dermatological solutions, this article summarizes current knowledge on plant-extract-loaded liposomal nanoformulations to guide future research toward their potential applications in dermatology and cosmetology.

Abstract: Hydrogels, three-dimensional hydrophilic polymer networks that can imbibe large volumes of water or biological fluids without dissolving, have become one of the most versatile platforms in pharmaceutical and biomaterial science. Their high water content, soft tissue-like mechanics, biocompatibility and tunable network architecture allow them to be engineered as topical, ophthalmic, mucosal, oral and injectable dosage forms and as scaffolds for regenerative medicine. This illustrated review provides a critical, practice-oriented account of the field, with particular emphasis on how hydrogel dosage forms are prepared. Physical cross-linking methods (ionic gelation, polyelectrolyte complexation, thermoresponsive gelation, freeze–thaw cycling and supramolecular assembly) and chemical cross-linking methods (free-radical and photo-initiated polymerization, small-molecule cross-linkers, click and dynamic covalent chemistries, and enzyme-mediated and radiation cross-linking) are examined in terms of their mechanisms, typical materials and conditions, critical process parameters, advantages and limitations. The preparation of conventional pharmaceutical gels based on carbomers, cellulose ethers, poloxamers and polysaccharides is described step by step, together with drug-loading strategies, processing into beads, micro- and nanogels, films, sponges, microneedles and printed constructs, and a troubleshooting guide for the most frequent formulation failures. Advanced architectures that overcome the intrinsic weakness of conventional networks, including hybrid, interpenetrating, nanocomposite, double-network and Tetra-PEG hydrogels, are then discussed, followed by the characterization and quality-control methods needed to establish critical quality attributes such as gel fraction, swelling and mesh size, rheology, morphology, release kinetics, stability, microbiological quality and biocompatibility. The review subsequently analyzes drug release mechanisms, route-specific delivery strategies, stimuli-responsive and hierarchical systems, the selection of drug candidates with reference to physicochemical properties and the Biopharmaceutics Classification System, and applications in tissue engineering and wound care. Finally, clinically approved products and the main translational barriers, namely mechanical fragility, burst release, residual reagents, sterilization, batch-to-batch variability and regulatory classification, are critically evaluated to identify realistic routes towards next-generation, clinically useful hydrogel dosage forms.

Abstract: Background: Patients with non-small cell lung cancer (NSCLC) increasingly receive oral targeted therapies and immune checkpoint inhibitors, creating complex medication-management and tox-icity-monitoring needs. Pharmacists may contribute through medication optimization, adherence support, patient education, drug-interaction management and multidisciplinary toxicity preven-tion. Objective: To map the published evidence describing pharmacist and pharmaceutical-care roles relevant to medication safety, adherence, toxicity management, and treatment continuity in NSCLC. Methods: A scoping review was conducted using PubMed/MEDLINE and Web of Science, supplemented by citation/other searching. The search was limited to English-language publica-tions from the 10-year period preceding the final search date (28 August 2016 to 28 August 2026). After reconciliation, 481 unique records were screened. Eligibility was assessed using an NSCLC-specific population criteria and pharmacy/pharmaceutical-care concept criteria. Evidence was classified as core/direct or contextual/supporting. The selection process was reported according to PRISMA-ScR. Results: Of 481 unique records screened, 444 were excluded at title/abstract screen-ing and 37 reports progressed to eligibility assessment. Twenty-two were excluded at eligibility, leaving 15 sources of evidence: 11 core/direct sources and four contextual/supporting sources. Core evidence covered medication optimization and drug–drug interactions, adherence monitoring, adverse-event/toxicity management, patient education, and pharmacist-led ambulatory or multi-disciplinary services. Conclusions: The evidence indicates that pharmacists can contribute mean-ingfully to medication safety, adherence, toxicity management, and treatment continuity in NSCLC. However, the evidence base remains heterogeneous and includes observational and con-textual sources. Larger prospective multicenter studies and economic evaluations are needed to establish the long-term clinical and health-system impact of standardized pharmacy services.

Abstract: Peptides are promoted as longevity and healthy-aging interventions, and US regulators are moving to widen access to unapproved ones. I asked which FDA-approved peptides have improved functional reserve and resilience in aging, measured as loaded function in older adults. Of 144 non-insulin peptide records from three published lists, 93 had current US prescribing information, and 26 of these could act on one of five physiological capacities that sustain reserve: bioenergetic capacity, endocrine signaling, proteostasis and mitochondrial quality control, hormetic stress response, and autonomic regulation. I searched PubMed for each. A peptide counted if a blinded controlled trial in older adults improved a loaded functional outcome such as walking capacity, strength or cognition. Five did, though only one has strong support. Semaglutide, tirzepatide and liraglutide improved walk distance; in two trials the gain rose with weight loss, and strength was not reported. Tesamorelin improved executive function in one trial of older adults. Teriparatide improved mobility after fracture but acts on bone, an actuator, rather than a regulatory capacity. None of the 26 moved a loaded outcome through proteostasis, hormesis or autonomic regulation, the targets claimed for unapproved longevity peptides such as BPC-157 and TB-500, which FDA found poorly characterized and without adequate human data. I set out the product-quality standards any peptide must meet before a clinical claim, and the endpoints that would make a claim about reserve falsifiable. Geroscience trials of peptides should require loaded functional endpoints and report reserve costs such as loss of lean mass and strength.

Abstract: Fixed-combination pharmaceutical forms offer the advantage of simple, reliable admin-istration of two different active substances. This study aimed to develop atorvastatin- and amlodipine-containing polymer-based fibrous sheets at a 1:4 dose ratio for fast disintegra-tion, enhancing elderly patient compliance. Polyvinyl pyrrolidone-based polymer disper-sion was embedded with two active ingredients via solubilization with polysorbate 80. The dispersions were described by pH, conductivity, and texture analysis. The fibrous sheets were characterized by morphology, disintegration, and dissolution. The single-jet electrospun fibers had an average diameter of 588 ± 190 nm. Differential Scanning Calo-rimetry (DSC) and Fourier Transform Infrared (FTIR) results suggest the amorphization of the active substances. Disintegration was very fast, with a measured time under 3 seconds. The API release occurs in a burst, with complete dissolution achieved within the first 5 minutes. The fixed-dose combination fibrous sheets offer a possible fast-delivery system for buccal administration in elderly patients.

Abstract: Bio-encoded nanostructures use nucleic-acid or protein sequence information to specify aspects of nanoscale assembly, ligand display, cargo organization, or stimulus-responsive function. Their pharmacological promise depends not only on whether a structure can be designed, but on whether the intended architecture survives manufacture and biological exposure, reaches the relevant compartment, produces target engagement, and does so with acceptable safety. This narrative review examines DNA and RNA nanostructures, self-assembling protein nanoparticles, virus-like particles, and selected biomimetic systems through a pharmacology-first lens. Rather than treating programmability as evidence of therapeutic superiority, it links design features to testable development questions: What product attributes must be measured? Which experiment can identify a failure in assembly, stability, biodistribution, intracellular delivery, or pharmacodynamic activity? What evidence is needed before a candidate advances? The review proposes a six-layer framework spanning molecular information, assembly, biological recognition, disposition, response, and translation, then converts it into a practical failure-analysis workflow with measurable readouts and decision points. The framework is a proposed development aid, not a validated predictive model or an established regulatory classification. Its value will depend on prospective testing against platform-specific datasets and demonstration that it improves experimental prioritization. By separating demonstrated findings from hypotheses and linking each design claim to an assay and a development decision, the review aims to help researchers more precisely diagnose translational bottlenecks and reduce the risk of advancing nanostructures based on in vitro programmability alone.

Abstract: Background: Manual IV medication preparation requires multiple discrete steps, each a potential point of process deviation, while manufacturer-prepared ready-to-use (MP-RTU) products avoid many manual compounding steps. Peer-reviewed literature describing and quantifying real-world process-error and workforce-time-waste (WTW) differences between traditional IV piggyback (IVPB) and MP-RTU products remains limited. Methods: Two complementary studies were conducted. The Alpha study was a prospective, direct-observation study of 100 micafungin (47 steps) and 100 norepinephrine (15 steps) preparations at a 541-bed hospital. The Bravo study was a retrospective operational analysis of utilization, request burden, time-to-administration, and preparation cost for four medications at a 615-bed hospital. Results informed a decision-analytic cost-effectiveness model (1-year horizon, health-system perspective) comparing MP-RTU with IVPB, with sensitivity analyses. Results: Micafungin preparations contained 208 process errors (4.4%; 67% with ≥ 1 error), concentrated in drug withdrawal, syringe assembly, and material collection; norepinephrine preparations contained 100 errors (6.7%; 70% with ≥ 1 error), concentrated in hood preparation/compounding. Pharmacy-prepared insulin and vasopressin showed higher request burden and roughly 2-hour longer time to administration than MP-RTU equivalents. MP-RTU dominated IVPB in the model, with a base-case incremental cost-effectiveness ratio of −$4,954.15 per additional error avoided, robust across sensitivity analyses. Conclusions: Manual IV preparation introduced process-error and operational-burden that was either reduced or absent with MP-RTU; this was also less costly and more effective in the model. Findings support considering process-error opportunity and operational burden, not acquisition cost alone, when evaluating IV medication-preparation strategies.

Abstract: Recombinant humanized collagen type III (rhCol III) has attracted growing interest as a biomaterial for tissue engineering, wound healing, and dermal fillers because of its excellent biocompatibility, low immunogenicity, and crucial role in tissue repair and regeneration. However, native rhCol III suffers from poor mechanical stability and rapid enzymatic degradation in vivo. Chemical crosslinking with 1,4-butanediol diglycidyl ether (BDDE) represents a well-established strategy to enhance the structural stability and application performance of collagen-based biomaterials. In this study, we present a comprehensive NMR spectroscopy investigation of BDDE-crosslinked rhCol III, combining one-dimensional (¹H and ¹³C) and two-dimensional (COSY, HSQC and HMBC) NMR experiments to definitively identify crosslinking sites, characterize reaction products, and quantify key crosslinking parameters. Using a recombinant type III collagen of approximately 55 kDa con-taining 18 lysine residues per molecule, we demonstrated that BDDE crosslinks collagen predominantly through covalent modification of the ε-amino groups of lysine residues under alkaline conditions. Quantitative NMR analysis determined key parameters including the degree of modi-fication (MoD), the crosslinker ratio (CrR), and the degree of crosslinking. Physicochemical characterization further showed that BDDE crosslinking markedly enhanced the thermal and mechanical stability of rhCol III, with the denaturation temperature increasing from 55.94 °C to 68.18 °C and the apparent viscosity improving by approximately 100-fold. Importantly, toxicity and safety as-sessment confirmed the biocompatibility of the crosslinked material. Collectively, these results establish a robust NMR-based characterization platform for BDDE-crosslinked collagen and demonstrate that the resulting biomaterial affords enhanced structural stability together with excellent biocompatibility, supporting its potential for tissue engineering and dermal filler applications.

Abstract: Background: Terminal sterilization is generally preferred for parenteral products when the formulation and container can tolerate the process. Retatrutide is a thermolabile peptide, making conventional moist heat unsuitable and creating a need to evaluate a nonthermal terminal modality. Objective: To establish an in silico decision framework for electron beam terminal sterilization of a 10 mg/mL retatrutide multidose cartridge and to define a stability indicating reversed phase high performance liquid chromatography method for post irradiation control. Methods: Moist heat, dry heat, ethylene oxide, sterile filtration with aseptic processing, and electron beam irradiation were compared by product specific criteria. A model electron accelerator configuration used a UELR-10-15-S-1 unit No. 128170401 at 9.5 MeV, 1.19 mA, 50 cm scan width, and 1.75 m/min conveyor speed. Three virtual batches were assigned dose maps, bioburden distributions, verification tests, sterility outcomes, and RP HPLC results. A Monte Carlo survivor model estimated the probability of a nonsterile unit. Results: The model selected electron beam irradiation as a candidate terminal method, subject to experimental qualification. Simulated minimum and maximum absorbed doses were 15.1 to 15.4 kGy and 18.1 to 18.4 kGy, respectively. All three virtual batches met the model criterion of a probability of a nonsterile unit not greater than 10 to the power of minus 6. Post irradiation retatrutide assay was 97.2 to 97.8 percent, while total related substances were 2.10 to 2.39 percent. Conclusions: The simulated dataset supports a bounded development hypothesis but does not demonstrate sterility, peptide integrity, process validation, or suitability for human use. Accelerator electrical settings do not define absorbed dose. Confirmatory work requires calibrated dose mapping, microbiological dose substantiation, validated RP HPLC and orthogonal structural and biological methods.

Abstract: The United States classifies drug products into two categories: those obtainable only on the authority of a licensed prescriber, and those obtainable without restriction. Proposals for an intermediate, pharmacist-mediated class have circulated since 1984, and the Food and Drug Administration’s 2024 rule permitting a nonprescription drug product with an additional condition for nonprescription use operationalizes a narrow version of the idea. What no proposal has supplied is the instrument such a system would require, the criteria by which the roughly 1,900 active pharmaceutical ingredients already on the market would be assigned to tiers. This paper constructs that instrument. It sets out four design decisions that precede any substantive criterion, adapts the published scheduling factors of Canada, Australia, the United Kingdom, and the European Union into a three-tier cascade, and adds a mandatory finding of the harm attributable to withholding, recorded for every product at every tier. It then applies the cascade to the marketed pharmacopoeia, proposing a review sequence in three cohorts and a continuation exemption under which established therapy is verified by the dispensing record already held at the point of sale. The framework is offered as a working draft for criticism rather than as a finished rule.

Abstract: Pharmaceutical indication and pharmacist prescribing have become strategies for expanding the capacity of primary care, particularly in the management of minor symptoms and low-complexity clinical conditions. This narrative review, guided by the SANRA domains, integrated scientific, regulatory, and institutional evidence identified through PubMed/MEDLINE, ScienceDirect, and Google Scholar, supplemented by grey literature from regulatory bodies, health services, and professional organizations, to comparatively characterize regulatory and practice models described across jurisdictions. Four main configurations were identified: pharmaceutical indication, protocol-based models, collaborative prescribing, and independent prescribing, with heterogeneous implementation internationally. Available evidence reports favorable outcomes in some services, including improved accessibility, high user satisfaction, and a potential shift in consultations from other healthcare settings to community pharmacy; however, heterogeneity in study designs, settings, and outcome measures, together with the predominance of observational and implementation studies, limits the certainty of these findings. Rather than demonstrating the superiority of a particular level of professional autonomy, the literature consistently shows that structured models incorporate clinical protocols, eligibility criteria, red-flag assessment, safety-netting, referral, and documentation. Effective implementation also requires consideration of professional training, care integration, documentation systems, and sustainable funding mechanisms. In Latin America and Costa Rica, the literature documents frequent pharmaceutical consultation and indication practices, although with variable levels of formalization and standardization.

Abstract: Background/Objectives: Postoperative management after cataract surgery involves topical anti-inflammatory and antimicrobial treatments, whose clinical performance may be affected by adherence, administration technique, and intraocular exposure. This study evaluated a biodegradable poly(lactic-co-glycolic acid) intracameral implant containing moxifloxacin hydrochloride and dexamethasone, designed for intraoperative placement. Methods: Clinical tolerability, anti-inflammatory activity in a uveitis model, and antibacterial performance following a low-inoculum intravitreal challenge with Pseudomonas aeruginosa were evaluated in New Zealand White rabbits. Aqueous humor pharmacokinetic profiles were also assessed in phakic and aphakic eyes. Clinical follow-up included slit-lamp biomicroscopy and intraocular pressure measurements. Concentration–time data were analyzed by means of nonlinear mixed-effects models and model-based simulations. Results: No visible implant material remained four weeks after insertion. A transient pseudo-membrane was observed shortly after implantation in some implanted eyes, but it resolved spontaneously and was not accompanied by clinical inflammatory signs. No sustained increase in intraocular pressure was observed during follow-up. Untreated bacterially challenged eyes rapidly developed severe endophthalmitis, whereas implant-treated eyes showed no clinical evidence of endophthalmitis. In the exploratory uveitis experiment, implant-treated eyes showed lower clinical inflammatory scores and faster recovery than matched eyes without the implant. Model-based simulations suggested persistent dexamethasone exposure through day 30, whereas moxifloxacin reached an early peak and was predominantly below the limit of quantification from day 7 onward. Conclusions: These findings provide preliminary preclinical proof-of-concept evidence supporting the clinical tolerability and pharmacological activity of the implant under the experimental conditions evaluated. The results are hypothesis-generating, should not be extrapolated to clinical safety or efficacy, and do not demonstrate microbiological eradication. Further studies with larger cohorts, pseudophakic models, microbiological and histopathological endpoints, and optimized pharmacokinetic sampling are required.

Abstract: Background: Benzodiazepine withdrawal is well documented, with some patients reporting symptoms that persist long-term. BIND (benzodiazepine-induced neurological dysfunction) is a term proposed to encompass the withdrawal symptoms following long-term benzodiazepine usage and discontinuation. Pharmacist awareness of this term and confidence in its management has not been assessed. This is important to characterize, as pharmacists have a role to play in ensuring medication safety and participating in counseling and collaborative tapering. Objectives: Assess (a) Colorado pharmacist awareness of persistent benzodiazepine withdrawal symptoms following discontinuation, and (b) whether brief educational exposure would alter perceptions and confidence. Methods: This two-stage, exploratory study used data from individuals reporting long-term symptoms following benzodiazepine discontinuation to inform a survey to licensed and practicing Colorado pharmacists. Pharmacists were assessed on their knowledge of the term BIND, impression of various long-term withdrawal symptoms, tapering strategies, and responses before and after a brief educational intervention. Descriptive statistics were used for survey items, Fisher exact testing for associations between categorical variables, and the Wilcoxon Signed Ranks Test for paired pre/post Likert-Type responses. Results: 100 pharmacists initiated the survey, and 62 met the inclusion criteria. 52 of the 62 respondents that qualified completed the survey in its entirety and were included in the primary analysis. Reported item-level denominators ranged from 55 to 62. Respondents had differing knowledge of BIND and reported limited confidence in identifying and managing symptoms of withdrawal. Though education resulted in a change in pharmacist perceptions, this was not statistically significant. Pharmacists who had prior knowledge of BIND and benzodiazepine withdrawal were significantly more likely to recognize associated symptoms in their patients (reported Fisher exact P=0.011). Respondents agreed that pharmacists play a specialized role in imparting benzodiazepine education to patients and providers but varied in their confidence to do so (median of 3 on a 0-5 Likert-Type scale from not confident to very confident; n=55). Conclusions: Pharmacist awareness of BIND and long-term benzodiazepine withdrawal symptoms appear to be limited. Though brief education may not be enough to alter clinical perceptions, this study identifies gaps in knowledge and the need for additional support to help pharmacists manage patients and educate others. Future directions include a need for similar studies with larger samples, validated survey measures, and standardized educational interventions. Results should not be interpreted as the validation of BIND as a diagnosis or establishing causality between benzodiazepine exposure and patient-reported persistent symptoms.

Abstract: Palatability critically determines pediatric medication adherence, yet the impact of oral cavity dilution and salivary pH on the sensory performance of formulations remains poorly characterized. This study provides the first systematic, biorelevant evaluation of how dilution and physiologically relevant pH affect the palatability of three commercially available hyoscine butylbromide (HBB) syrup brands (X, Y, and Z), extending prior characterization of undiluted formulations. Samples were evaluated using an Alpha Astree II electronic tongue (ChemFET array). Dilution with water and with 2 mL or 5 mL phosphate-buffered saline (PBS) at pH 6.2, 6.8, and 7.4 replicated residual salivary volumes and physiological pH across pediatric and adult populations. Pure HBB API solutions were tested in parallel. Principal component analysis (>85% cumulative variance) confirmed robust discrimination across all conditions. Water dilution increased bitterness across all brands by disrupting excipient matrix integrity, with cellulosic polymer-containing Brands X (HEC) and Y (HPMC) retaining superior taste masking over polymer-free Brand Z. PBS dilution revealed pH-dependent, brand-specific palatability responses: at pH 6.2, 6.8, and 7.4, the hierarchy was consistently Y > X > Z, confirming the robust superiority of Brand Y's HPMC-based taste-masking system across the full physiological salivary pH range. Notably, Brand X exhibited substantially higher ANS sweetness scores than Brand Y at 2 mL pH 7.4 PBS, reflecting differential sweetener system sensitivity to near-neutral PBS ionic conditions. Increasing simulated salivary volume from 2 mL to 5 mL amplified bitterness and attenuated sourness across all brands. Taste-masking strategies that rely solely on sweeteners, without viscosity-building polymers, are inadequate under biorelevant oral conditions. pH-stratified assessment is essential for comprehensive characterization of palatability in pediatric oral liquid formulations.