Multiple Daily Doses Research Articles

Disclosure: S. Choudhury: None. K. Lazarus: None. A. Sharma: None. K. Narula: None. C. Go: None. S. Cro: None. T. Thaventhiran: None. B. Khoo: None. T. Tan: None. K. Meeran: None.Background: Prednisolone is the active and biochemically equivalent form of prednisone after conversion by the liver in first pass metabolism. It is a separate drug to methyl-prednisolone. Once daily low dose prednisolone is an alternative treatment to standard thrice daily hydrocortisone, for the treatment of adrenal insufficiency. We present findings from the first ever clinical trial comparing once daily low dose prednisolone with thrice daily hydrocortisone. Methods: This double-blind randomised crossover study treated patients with adrenal insufficiency using either 4 months of low dose prednisolone (2-4 mg) with matching placebo at noon and in the afternoon, or 4 months of standard regimen hydrocortisone (10 / 5 / 2.5 mg) in the first study period, followed by the alternative medication in the second study period. Anthropometrics, biochemical data for cardiometabolic and bone health, and subjective health survey data were collected at Day 1, 30 and 120 of each study period. Results: There was a significant reduction in body weight at 4 months, with a treatment difference of -1.87 Kg (p=0.002) favouring prednisolone treatment. Concordant treatment differences in waist circumference and HbA1c of -2.26 cm (p=0.010) and -1.23 mmol/mol (p=0.001) were also detected. Short term and medium-term bone formation markers were suppressed on prednisolone with a treatment difference of -1.22 µg/L (p=0.035) in osteocalcin levels and -13.8 ng/L (p<0.001) in Procollagen 1 N-Terminal Propeptide. Urinary N-telopeptide levels, a bone resorption marker was also suppressed by -9.34 nmol/mmol (p=0.002) associated with prednisolone. Other cardiovascular markers such as blood pressure, high-sensitivity troponin and CRP, did not show significant differences between prednisolone and hydrocortisone. Subjective health outcomes were measured by the SF-36 survey and Addisons Quality of Life (Addi-QoL) questionnaire. There was no significant difference in any of the SF-36 domains including physical functioning, emotional wellbeing or general health. Addi-QoL scores were comparable between both treatments. Discussion: Once daily low dose prednisolone or prednisone is a safe alternative to thrice daily hydrocortisone to treat adrenal insufficiency, without compromising wellbeing. There is evidence of improved cardiometabolic and glycaemic outcomes with prednisolone. This may be because hydrocortisone is associated with uncoupling from the normal physiological profile of cortisol, or multiple daily doses causing increased steroid exposure. Conclusion: This study supports the routine use of low dose prednisolone, which would further permit longer term studies using real world mortality and morbidity outcomes.Presentation: Saturday, July 12, 2025

Hypersensitized P2X3 receptor signaling has been described to play a role in several disorders, including chronic cough. The goal of our in vitro and in vivo studies was to investigate the biotransformation and the influence of CYP3A4 inhibition on the pharmacokinetics of the selective P2X3 antagonist filapixant. Metabolic turnover of filapixant in human liver microsomes and hepatocytes was moderate to high, indicating a complex metabolic pattern with mainly oxidative biotransformation. In recombinant CYP enzymes, depletion of filapixant was observed mainly with CYP3A4 and, to a significantly lesser extent, with CYP1A1, 2D6, 2J2, and 3A5. Drug depletion of [3H]filapixant and metabolite formation in human liver microsomes was significantly inhibited in the presence of strong CYP3A4 inhibitors, whereas other CYP isoform–selective inhibitors showed no or very minor effects. Co-administration of multiple daily doses of 200 mg itraconazole with 80 mg filapixant in humans increased the AUC and Cmax of filapixant to 4.01 and 1.89-fold, respectively, indicating that filapixant is a moderately sensitive CYP3A4 substrate. Co-administration of itraconazole also prolonged the half-life of filapixant from 12.1 h to 22.8 h. Overall, changes in AUC, Cmax, and half-life indicate that both the bioavailability and elimination of filapixant were affected. Filapixant was well tolerated alone and in combination with itraconazole.

Buprenorphine use in pregnancy and postpartum for individuals with opioid use disorder (OUD) decreases maternal and fetal morbidity and mortality. Extended-release buprenorphine overcomes barriers to sublingual buprenorphine, but very limited data are available regarding use in the perinatal period. We aimed to describe extended-release buprenorphine uptake and associated recovery and pregnancy outcomes in a case series of 15 pregnant and postpartum individuals with OUD. Reasons for extended-release buprenorphine initiation included nausea, burdensome multiple daily dosing of sublingual buprenorphine, and persistent cravings. Postinitiation, all patients demonstrated increased buprenorphine adherence, total cessation of nonprescribed opioids, and a reduction in other substance use. There were no identified maternal or neonatal side effects. Our data provide early evidence for safety, adherence, and reduced substance use among perinatal patients with OUD treated with extended-release buprenorphine.

Comparison of antimicrobial consumption indicators in the emergency department.

Motion sickness (MS) is a common phenomenon in life and nearly all individuals will experience MS at least once in their lives. Diphenidol hydrochloride (DPN) is widely used in China for the pharmacotherapy of MS at the dosages of 25 mg every 6–8 h as needed. The conventional DPN tablets may present inconvenience for individuals embarking on extended sea voyages, as they require multiple daily doses. The aim of this study was to develop and assess in vitro a novel tablet-in-tablet (TIT) formulation of DPN, which serves as a single-dose unit designed to facilitate rapid and extended drug release. Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) analyses were employed to investigate the possible interactions between DPN and adjuvants in the pre-formulation study. Direct compression (DC) technique was employed to fabricate the tablet, employing microcrystalline cellulose (MCC) and polyethylene oxide (PEO) as release modifying agents. The study investigated the influence of MCC and PEO, each at various weights, on the in vitro drug release and swelling index of core-tablets using a response surface method (RSM) of Miscellaneous (3-level Factorial) design. It demonstrated that an increase in PEO content enhanced drug release, whereas the inclusion of MCC exerted a suppressive influence on release. The core tablet was press-coated with an outer instant-release shell, which composed of MCC and cross-linked sodium carboxymethylcellulose (CMC) in three distinct weight. Both the core-tablet and TIT exhibited desirable physicochemical properties. Optimized formulation of the core-tablet (PEO 100 mg, MCC 70 mg) achieved a 90% of drug release in vitro after 12 h and a swelling index of 52%. The final TIT formulation (Core tablet: PEO 100 mg, MCC 70 mg; Outer shell: PEO 70 mg, MCC 300 mg) was finally obtained with reduced excipient content and shorter disintegration time. The developed TIT formulation of DPN may offer a promising approach for improving the convenience and efficacy of MS treatment by providing both immediate and extended drug release from a single dosage form.

ABSTRACTBackgroundAdherence to 5‐aminosalicylic acid (5‐ASA), an anchor drug for ulcerative colitis (UC), affects remission maintenance. This study aimed to investigate the current status of adherence to 5‐ASA and identify the factors associated with adherence.MethodsWe enrolled UC patients whose primary maintenance therapy was oral 5‐ASA at our hospital between January 2017 and December 2018. The adherence status was examined using a questionnaire survey. Various factors, including patient background and disease activity, were also analyzed to identify those related to adherence. A second questionnaire with the same content was performed 1 year after the initial survey for comparison.ResultsIn total, 297 patients with UC answered the first questionnaire, of which 278 answered the second questionnaire. Complete adherence rates at the time of the first and second questionnaires were 49.8% (148/297) and 55.8% (155/278), respectively. Full‐time employment (p = 0.00893), eating one or two meals per day (p = 0.00641), and multiple daily doses (p = 0.0153) were significantly associated with lower adherence. The 119 patients who fully adhered to both the primary and secondary questionnaires had a significantly higher cumulative non‐relapse rate at 1 year than those 159 who were not (85.7% vs. 76.1%, p = 0.0207).ConclusionsUC patients with high adherence to 5‐ASA showed a high rate of remission maintenance, so adherence should be improved by considering factors such as the number of medications taken, work status, and dietary habits.

Malaria drug interactions in cytostatic or inhibitory in vitro assays or suppression models in vivo can be different than curative killing interactions. In the pharmacodynamic high parasitemia Plasmodium berghei ANKA-luciferase mouse blood-stage model, we investigated curative interaction analysis of multiple, daily dosed, short half-life, artesunate or single-dose, long half-life, pyronaridine against three single-dose, long half-life, quinolines-chloroquine, amodiaquine, and tafenoquine. Positive or negative parasiticidal activity measured by parasite reduction rate in the days post-treatment correlated nonspecifically to final curative interactions. Tafenoquine/artesunate and pyronaridine/amodiaquine also had fractional combination curative doses of 0.83 and 0.93, with the rest of the interactions closer to neutral at 0.9-1.1. All tested combinations are in the additive drug interaction range. Time to return of initial parasitemia in subcurative regimens was also imprecise for the prediction of cure with combinations. Short blood half-life azithromycin, requiring multiple daily doses, was additive to artesunate or pyronaridine in fractional curative dose combination killing. Murine malaria high parasitemia drug interactions at the curative metric in vivo are a potential benchmark for human studies.

Casdatifan is an orally bioavailable small-molecule hypoxia-inducible factor-2α (HIF-2α) inhibitor currently in development for treating patients with clear cell renal cell carcinomas. The aim of this study was to characterize the pharmacokinetics (PK), pharmacodynamics and safety of casdatifan in healthy participants. This first-in-human study (NCT05117554) investigating casdatifan in 70 healthy participants consisted of 3 parts: a double-blind, randomized, placebo-controlled single ascending dose (3-100 mg) part; a multiple ascending dose (15-50 mg once daily) part; and an open-label, fixed sequence, 2-period, drug-drug interaction part to evaluate the effect of multiple doses of casdatifan on the single-dose PK of midazolam. In healthy participants, casdatifan plasma exposure increased dose proportionally over a single dose of 3-100 mg and multiple daily doses of 15-50 mg. The mean half-life of casdatifan was approximately 24 h, and PK parameters did not change over time. Dose- and concentration-dependent reduction, ranging from 41 to 85%, in erythropoietin (a pharmacodynamic biomarker for peripheral, nontumour, HIF-2α inhibition) was observed after single and multiple doses, consistent with HIF-2α pathway inhibition. Results from the midazolam drug-drug interaction part indicated that casdatifan was a weak CYP3A4 inducer at the tested dose. Urine PK data showed that approximately 30% of the overall casdatifan clearance appears to be via renal clearance. Casdatifan, after single and multiple dosing in healthy participants, was safe and tolerable. Linear PK was associated with a mean maximum erythropoietin reduction of 85% following a single dose and multiple doses of casdatifan, demonstrating a promising exposure-biological activity profile.

Obicetrapib, a selective cholesteryl ester transfer protein inhibitor in development for the treatment of dyslipidemia and cardiovascular risk, is expected to be administered with high-intensity statins in clinical practice. This study was performed to assess the effect of obicetrapib on the pharmacokinetics (PK) of atorvastatin and rosuvastatin. An open-label study was conducted to evaluate the PK of atorvastatin 80mg (cohort 1, n=42) or rosuvastatin 40mg (cohort 2, n=32, non-Asians) with and without co-administration of 10mg obicetrapib in healthy adult males and females. Study participants received statin on day -4, obicetrapib on days 1-11, statin co-administered with obicetrapib on day 12, and obicetrapib on days 13-17. Blood samples were collected throughout the dosing period and analyzed for plasma obicetrapib (both cohorts); atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy atorvastatin (cohort 1), and rosuvastatin (cohort 2). Safety and tolerability were also assessed. The 90% confidence intervals of the geometric mean ratios for the log-transformed maximum plasma concentration and area under the curve from time 0 to the time of the last measurable concentration (AUCt) and from time 0 to infinity (AUCinf) for atorvastatin and rosuvastatin were all within the range pre-specified for bioequivalence (80.00-125.00%) of statin plus obicetrapib versus statin alone. Although there were significant treatment effects for atorvastatin AUCt (p=0.0026) and AUCinf (p=0.0012), the differences were small (9-10%) and not deemed clinically important. Overall, all study drugs were safe and well tolerated. No clinically significant PK interaction occurred between multiple daily doses of obicetrapib on the single-dose PK of either atorvastatin or rosuvastatin in healthy volunteers. NCT06081166.

Single daily dose prednisolone has a lower cardiovascular risk compared to multiple daily hydrocortisone doses in patients with adrenal insufficiency

Due to its short plasma half-life, clozapine is typically prescribed in a divided dosing regimen. Although once-daily dosing has proven effective in countries such as Japan, South Korea, Canada, and the United States, its adoption in real-world clinical practice in China remains unclear. This study aimed to compare patient characteristics, psychiatric symptoms, side effects, and plasma clozapine concentrations between once-daily and divided dosing regimens, and to determine the dosage required to achieve plasma levels of 350-600ng/mL in the Chinese population. We conducted a single-center, retrospective, cross-sectional study at Xi'an Mental Health Center, China, collecting data on clozapine-treated patients from March 2019 to March 2021. Most patients (80% of 198) in the Chinese cohort followed a divided-dose regimen in clinical practice. In the once-daily dosing group, the average plasma clozapine concentration was 158.75ng/mL, with only 8% of patients reaching the therapeutic window. Conversely, patients on a divided dosing regimen had significantly higher plasma concentrations, averaging 373.34ng/mL, with 28% within the therapeutic window. The psychiatric symptom remission rate did not differ significantly between the once-daily and divided-dosing groups (50.05% vs. 52.72%, p=0.718); however, the divided-dosing group experienced a greater variety of adverse effects. Receiver operating characteristic analysis indicated that patients on multiple daily doses require a total daily clozapine dose of 150-250mg to achieve the target plasma concentration, corresponding to a clozapine concentration-to-dose ratio of 1.4-2.4. Chinese clinicians generally adhere to a divided dosing schedule for clozapine when the daily dose exceeds 50mg. Further prospective longitudinal studies are warranted to evaluate whether once-daily dosing regimens can improve clinical outcomes.

Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic disorder that causes bone abnormalities due to hypophosphatemic rickets and skeletal dysplasia and is a significant health comorbidity. Conventional therapy involving multiple daily oral doses of phosphate and calcitriol for CSHS patients has limited effectiveness. We report the clinical features and therapeutic outcomes of the first Chinese child diagnosed with CSHS, who presented with bone fractures, a history of seizures, and recurrent gastrointestinal manifestations, including diarrhoea and bowel obstruction. The effectiveness of conventional therapy and an anti-FGF23 antibody (burosumab) was evaluated. Ultra-deep sequencing was performed on the patient's blood DNA, skin tissue, oral mucosa, and hair follicles to identify causative mutations. The child had a somatic mutation in the HRAS (p.G13R) gene, which was identified at low variant allele frequencies. We analysed the sequencing results from reported cases and determined that the sequencing of lesional tissues, such as skin and bone, is preferable to that of oral mucosa or potentially affected hair follicles for establishing a definitive diagnosis of CSHS. Compared with conventional phosphate therapy, burosumab resulted in a steady increase in blood phosphorus levels and significant improvements in patient mobility, pain outcomes and skeletal radiography. It is suggested that younger children may receive a higher initial dosage of burosumab for better outcomes. However, long-term follow-up is still necessary to confirm its efficacy and safety.

Prothioconazole (PTC), a widely used triazole fungicide with low human toxicity, was evaluated for its potential to inhibit human cytochrome P450 (CYP450) enzymes and its implications for pesticide-drug interactions (PDI). Through in vitro assays, PTC demonstrated significant inhibition of CYP2C9, CYP2C19, and CYP3A, with inhibition constant (Ki) values ranging from 0.08 to 5.88µmol L⁻1. Initial predictions using a basic static model suggested potential for PDI, particularly with CYP2C9 substrates. To refine these predictions, a physiologically-based pharmacokinetic (PBPK) rat model was developed using mass balance studies and pharmacokinetic data across doses of 2 and 150mgkg-1. The model's accuracy was confirmed by simulated versus observed maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) values, with errors remaining within two-fold. The rat model was subsequently extrapolated to humans using in vitro binding and metabolism data. Simulations with 10 virtual trials, each involving 10 fasted human subjects, assessed PDI potential under multiple daily doses of PTC at multiples of the acceptable daily intake (ADI, 0.05mgkg-1). AUC ratios for CYP3A (midazolam, nifedipine), CYP2C19 (omeprazole), and CYP2C9 (tolbutamide) substrates indicated no significant inhibition at ADI levels. This study underscores the safety of PTC in terms of PDIs at dietary exposure levels and highlights the utility of PBPK modeling as a robust tool for pesticide risk assessment. The findings strengthen confidence in PTC's safety for human health.

FreeStyle Libre (FSL) monitoring is available for all patients in Wales with insulin-treated diabetes. English guidance permits FSL in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) requiring multiple daily insulin doses (MDI) (National Institute for Health and Care Excellence 2023). The literature suggests benefits from using FSL, specifically improved glycaemic control and reduced hypoglycaemia. Patients aged >18 years with insulin-treated T2D using FSL for ≥ 3 months were identified from Libreview. Those with pre- and post-FSL HbA1c were included. Days 1-14 of FSL data were taken as baseline. Patients were categorised by insulin regime (OD basal, premixed, basal bolus). 236 patients were identified and 189 patients included. The median follow-up duration was 14.6 [10.3-15.0] months. There were significant reductions in median HbA1c [8 mmol/mol, p < 0.001], time below range [< 4.0 mmol/L](1.2 ± 3.4 vs 0.6 ± 1.5%, p = 0.01), and low glucose average duration [52.1 ± 77.3 vs 35.6 ± 58.7 min, p = 0.01]. HbA1c improvements were greatest in OD basal [12 mmol/mol, p < 0.001] and pre-mixed [12.5 mmol/mol, p < 0.001] insulin regimes. Those taking premixed insulin had an increased time in target [7%, p < 0.05], reduced time above target [5.5%, p < 0.05] and reduced average glucose [0.3 mmol/L, p < 0.05] and GMI [2 mmol/mol, p < 0.01]. Patients on basal bolus insulin had significantly reduced time below range [0.5% p < 0.05]. Improvements in HbA1c were greatest in those taking OD basal or premixed insulins. Reductions in hypoglycaemia are likely to positively impact quality of life. Further studies will elucidate whether these improvements are directly related to improved quality of glycaemic data facilitating closer treatment titration, or behaviour changes related to FSL use.

BackgroundMedication non‐adherence is a leading cause of treatment failure in psychiatric populations. However, current studies highlight the lack of methodological guidance on medication assessments. Ecological Momentary Assessment (EMA), using smartphone‐based evaluations, shows promise for real‐time monitoring in everyday settings.AimsThis study evaluated EMA's effectiveness in assessing medication adherence in patients with schizophrenia, depression, and substance use disorders (SUD), covering various treatment regimens.Materials & MethodsA total of 133 participants (27 with schizophrenia, 20 with depression, 44 with SUDs, and 42 healthy controls) completed EMA via study‐provided smartphones five times daily over 1 week. Treatment regimens, categorized by mono vs. polytherapy and single vs. multiple daily doses, were documented. EMA adherence was calculated from the completion rate of the assessments, while medication adherence was assessed daily for patients. Both mean medication adherence and adherence variation over time were analysed by diagnosis and treatment regimen.ResultsAll groups demonstrated high mean EMA and medication adherence, with minor variations across treatment types. Importantly, patients showed improved adherence over time, independently of diagnosis or regimen.DiscussionThese findings indicate EMA's potential as an effective method for capturing medication adherence in psychiatric populations.ConclusionThe approach's capacity for real‐time, context‐sensitive data collection could reveal adherence patterns and changes not detectable by conventional methods, offering valuable insights for clinical practice.

Buspirone hydrochloride (BSP) is an anxiolytic agent approved for the management of anxiety disorders. The current US-FDA approved medications of BSP are administered via the oral route, which is linked to several disadvantages such as low oral bioavailability and low half-life necessitating multiple daily doses. For chronic diseases such as anxiety disorders, where long-term or lifelong management is often required, these factors impact patient compliance and treatment adherence. The present study offers an alternative treatment approach by investigating the feasibility of sustained transdermal delivery of BSP via long-acting microneedles (MNs). Needle-tip-loaded MNs were fabricated via micro-molding technique using various grades of poly-vinyl alcohol (PVA) namely 4–88, 8–88, 18–88, and 26–88. These MNs were compared using characterization techniques such as Parafilm® insertion testing, scanning electron microscopy (SEM), confocal microscopy, Fourier transform infrared spectroscopy (FTIR), and histological evaluation of MNs-treated human skin. The effect of different grades of PVA on the structural and mechanical properties of the fabricated MNs was evaluated. Further, in vitro release and permeation tests were conducted to assess the drug release patterns and transdermal delivery across dermatomed human skin over 7-day study periods. The highest release (5507.37 ± 456.88 µg/cm2) and delivery (4705.42 ± 634.57 µg/cm2) were observed from PVA 4–88, with significant differences among the PVA grades based on their properties. Notably, all four types of the fabricated PVA MNs crossed the daily and weekly therapeutic targets for the systemic delivery of BSP. Overall, this study established the feasibility of sustained delivery of BSP across the skin using PVA MNs for the management of anxiety disorders.Graphical

Background and Objectives: Chronic obstructive pulmonary disease (COPD) remains a critical global health challenge, characterized by high morbidity, mortality, and healthcare costs. Current guidelines may overlook patients who present with only one moderate exacerbation or with frequent short-acting beta-agonist (SABA) use. Building on findings from the Seleida study, this research refines the criteria for poor COPD control to include these patients, aiming to improve early identification of high-risk cases in primary care. Methods: A retrospectiveand multicenter study is conducted using data from 110 COPD patients in Spain. Poor control is redefined as having at least one moderate exacerbation or as using three or more SABA inhalers annually. Key predictors, such as SABA/short-acting muscarinic antagonist (SAMA) inhalers and antibiotic prescriptions, are identified using logistic regression and LASSO regularization to enhance predictive accuracy. Results: The model achieves a good predictive performance, with an AUC-ROC of 0.978, sensitivity of 92.86%, and specificity of 87.50%. Key predictors reliably identify high-risk patients, enabling timely interventions. This study demonstrates a statistically significant association between once-daily inhaler therapies and better COPD control compared to multiple daily doses, supported by chi-square analysis (p = 0.008) and binary logistic regression (p = 0.018). Nevertheless, the variable 'daily inhalation frequency' (1 vs. >1 inhalation/day) was excluded from the final model to prevent overfitting. Conclusions: By refining the criteria for COPD control to include patients with at least one moderate exacerbation or frequent SABA use, this model provides a practical tool for early risk stratification in primary care, particularly in resource-limited settings. Early identification of high-risk patients can reduce hospitalizations and healthcare costs, supporting a proactive approach to COPD management. Further validation in larger cohorts is essential to confirm its broader applicability.

AimsGLP‐1 receptor agonists (GLP‐1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non‐clinical and first‐in‐human (FIH) evaluation of ECC5004/AZD5004, an oral small‐molecule GLP‐1 RA.Materials and MethodsECC5004 was profiled in cell lines overexpressing human GLP‐1R, in glucose‐stimulated insulin secretion (GSIS) assays in a human β‐cell line and non‐human primates (NHPs). To evaluate safety, ECC5004 was orally administered to NHPs for 9 months and a phase I, double‐blind, placebo‐controlled FIH study was conducted. This study evaluated single doses of ECC5004 (1–300 mg) in healthy volunteers, and multiple daily doses (5, 10, 30 and 50 mg) in patients with T2DM for 28 days.ResultsECC5004 bound to the hGLP‐1R (IC50 = 2.4 nM) augmented cAMP signalling without β‐arrestin‐2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC‐βH5 cells (EC50 = 5.9 nM) and in vivo in NHPs (EC50 = 0.022 nM). Dose‐dependent body weight changes compared to control were seen in the 9‐month NHP toxicity study. In the first‐in‐human study, ECC5004 was well tolerated with no serious adverse events. Dose‐dependent reductions in glucose and body weight were observed with a dose‐proportional exposure at doses ≥25 mg.ConclusionECC5004 engaged the GLP‐1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP‐1 RAs, along with a pharmacokinetic profile compatible with once‐daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. Clinical trial registration: NCT05654831.

Aim: To formulate and evaluate the controlled-release Dicyclomine tablets using Araucaria columnaris gum as a natural polymer. Methods: The gum was extracted, purified and evaluated for its physical &amp; chemical properties, such as swelling capacity, viscosity and compatibility with the active pharmaceutical ingredient. Tablets were prepared with different concentrations of Araucaria columnaris gum (10-30% w/w) and assessed for pre-compression parameters including flowability as well as post-compression characteristics like hardness, friability, weight consistency and drug content uniformity. Results: Dissolution studies were carried out in-vitro using a USP Type II apparatus, simulating gastric conditions (pH:1.2) for the first two hours, followed by a phosphate buffer solution (pH:6.8) for the subsequent 10 hours. Drug release data were fitted into various kinetic models to evaluate the release mechanism, with the optimal formulation demonstrating extended release over 12 hours through a combination of diffusion and polymer matrix erosion. Conclusion: This study highlights the suitability of Araucaria columnaris gum as an effective matrix-forming agent for controlled-release tablets, reducing the need for multiple daily doses and improving treatment outcomes for dicyclomine hydrochloride.

Outpatient parenteral antimicrobial therapy (OPAT) is safe, effective and increasingly available. While OPAT in Norwegian healthcare has been rare, a new continuous ambulatory delivery device (CADD) allowing multiple daily dosing treatments has been innovated making OPAT more accessible. To describe the clinical outcome and safety using CADD in an OPAT setting. Adult patients in need of parenteral antibiotic treatment were offered OPAT and discharged with a programmable digital infusion pump allowing multiple daily dosings. Altogether, 170 patients were included in the study, among which 21% of all patients (36 of 170) were readmitted to hospital while receiving OPAT or within 30 days after end of intravenous antibiotics. None of the 170 patients died due to OPAT and allergies were not noticeable as a problem. We have developed a safe and clinically effective programme offering OPAT in accordance with Norwegian antibiotic treatment guidelines.