Search Results (24)

Chronic kidney disease (CKD) is a global health burden that affects close to one billion individuals. As many healthcare systems struggle to accommodate existing patients, CKD incidence and related costs are projected to continue rising. Based on a systematic search, this narrative review offers an in-depth assessment of advances in CKD pharmacotherapy published between 2020 and 2025, with a specific emphasis on drug combinations. Various treatment approaches for CKD exist, many of them targeting different mechanisms. Therefore, combining multiple medications could provide patients with better outcomes, though this comes with the risk of increased adverse effects and unnecessary costs. Alternatively, using biomarkers presents an opportunity to ascertain the most appropriate treatments specifically tailored to an individual’s molecular profile, thus personalizing CKD management. The second part of this review presents the current state-of-the-art methods to guide CKD therapy based on markers predicting treatment response. Collectively, this review presents possible pathways toward more effective CKD treatment. Full article

Introduction: There are no clear predictors of high-sensitivity C-reactive protein (hsCRP) reductions following the use of antihypertensives and statins. Also, there are no clear data on the effect of BMI on hsCRP changes following the use of antihypertensives and statins. Therefore, we sought to identify predictors of significant hsCRP reduction after the use of rosuvastatin (RSV)/amlodipine (AML) and atorvastatin (ATV)/AML. Methods: We included 237 patients from 21 institutions in the Republic of Korea. Patients were randomly assigned to one of three treatment groups: RSV 10 mg/AML 5 mg; RSV 20 mg/AML 5 mg; or ATV 20 mg/AML 5 mg. Multivariate logistic regression analysis was performed to evaluate the predictors for hsCRP responders (hsCRP reduction ≥ 40% after 8 weeks). We also compared baseline hsCRP levels and their changes after 8 weeks between obese patients (n = 153) and nonobese patients (n = 84). Results: Baseline hsCRP ≥ 2 mg/dL and RSV 20 mg/AML 5 mg were independent predictors of hsCRP responders. Their median hsCRP % change rates were −53.11% and −40.0%, respectively. Normal weight, pre-obesity, and obesity were not independent predictors of hsCRP responders. The median hsCRP % reduction rates among normal weight, pre-obese, and obese patients were less than 40% in all groups, and the differences between each group were not significant (−20.0% vs. −33.33 vs. −23.08%, p = 0.289). Conclusions: In patients with ATV, RSV/AML polypill, baseline hsCRP ≥ 2 mg/dL, and baseline RSV 20 mg/AML 5 mg were independent predictors of a significant hsCRP reduction. BMI was not associated with hsCRP reduction (Clinical trial: NCT03951207). Full article

Background/Objectives. Central nervous system (CNS)-related diseases such as Alzheimer’s and Parkinson’s, Attention Deficit Hyperactive Disorder (ADHD), stroke, epilepsy, and migraines are leading causes of morbidity and disability worldwide. New solutions for drug delivery are increasingly needed. In this context, three-dimensional (3D) printing technology has introduced innovative alternatives to produce more efficient medicines with diverse features, patterns, and consistencies, particularly oral medications. Even though research in this area is growing rapidly, no study has thoroughly analyzed 3D printing oral drug delivery progress for the CNS. To fill this gap this study pursues to determine a technological landscape in this field. Methods. For this aim, a Competitive Technology Intelligence (CTI) methodology was applied, examining 747 publications from 1 January 2019 to 20 May 2024 published in the Scopus database. Results. The main advances identified comprise six categories: 3D printing techniques, characteristics and applications, materials, design factors, user acceptance, and quality processes. FDM was identified as the main technique for pharmaceutical use. The main applications include pills, polypills, caplets, gel caps, multitablets, orodispersible films, and tablets, featuring external patterns and internal structures with one or more active substances. Insights show that the most utilized materials are thermoplastic polymers like PLA, PVA, PCL, ABS, and HIPS. A novel design factor involves release patterns using compartments of varying thicknesses and volumes in the core. Additionally, advances in specialized software have enabled the creation of highly complex designs. In the user acceptance category, oral drugs dosages are tailored to the specific needs and preferences of neurological patients. Finally, for the quality aspect, the precision in Active Pharmaceutical Ingredient (API) dosage and controlled-release mechanisms are critical, given the narrow margin between therapeutic doses and toxicity for CNS diseases. Conclusions. Revealing these advancements in 3D printing for oral drug delivery allows researchers, academics, and decision-makers to identify opportunities and allocate resources efficiently, promising enhanced oral medicaments for the health and well-being of individuals suffering from CNS disorders. Full article

Background/Objectives: The pharmacy profession has undergone significant changes driven by advancements in patient care and healthcare systems. The FDA approval of Spritam^® (levetiracetam), the first 3D-printed drug, has sparked increased interest in the use of Fused Deposition Modeling (FDM) 3D printing for pharmaceutical applications, particularly in the production of polypills. Methods: This review provides an overview of FDM 3D printing in the development of pharmaceutical dosage forms, focusing on its operation, printing parameters, materials, additives, advantages, and limitations. Key aspects, such as the ability to personalize medication and the challenges associated with the technique, including drug stability at high temperatures, are discussed. Results: Fourteen studies relevant to FDM 3D-printed polypills were analyzed from an initial pool of 60. The increasing number of publications highlights the growing global interest in this technology, with the UK contributing the highest number of studies. Conclusions: FDM 3D printing offers significant potential for personalized medicine by enabling precise control over dosage forms and tailoring treatments to individual patient needs. However, limitations such as high printing temperatures and the lack of standardized GMP guidelines for large-scale production must be addressed to fully realize its potential in pharmaceutical manufacturing. Full article

Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control of cardiovascular risk factors. Among these reasons, patients’ poor adherence to treatment regimens as well as limited rates of evidence-based therapy prescription from healthcare providers play a substantial role in the challenge of cardiovascular risk management. Polypills are fixed-dose combinations including two or more active drugs, from different pharmacological classes, combined in a single dosage form. Polypills were designed to simplify the clinical management of pharmacotherapy and increase adherence to treatment. From this perspective, we discuss the current literature on the use of polypills in the primary and secondary prevention of cardiovascular disease as well as future challenges and the potentials of this treatment strategy. Full article

Despite the availability of affordable pharmaceuticals treating cardiovascular diseases (CVDs), many of the risk factors remain poorly controlled. Fixed-dose combinations (FDCs), a form of incremental innovation, have already demonstrated improvements over combinations of single medicines in adherence and hard clinical endpoints. Nevertheless, there are many barriers related to the wider use of FDCs in CVDs. Our aim was to identify these barriers and explore system-level facilitators from a multi-stakeholder perspective. Identified barriers include (i) hurdles in evidence generation for manufacturers, (ii) limited acceptance of adherence as an endpoint by clinical guideline developers and policymakers, (iii) limited options for a price premium for incremental innovation for healthcare payers, (iv) limited availability of real-world evidence, and (v) methodological issues to measure improved adherence. Initiatives to standardize and link healthcare databases in European countries, movements towards improved patient centricity in healthcare, and extended value assessment provide opportunities to capture the benefits of FDCs. Still, there is an emerging need to facilitate the generalizability of sporadic clinical evidence across different FDCs and to improve adherence measures. Finally, healthcare payers need to be convinced to pay a fair premium price for the added value of FDCs to incentivize incremental innovation in CVD treatment. Full article

Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 and 2016, the burden of CVD remains disproportionately higher in low- and middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at the prevention and treatment of CVD are currently available, poor adherence, early discontinuation of treatment, and suboptimal daily execution of the prescribed therapeutic regimes give rise to shortfalls in drug exposure, leading to high variability in the responses to the prescribed medications. Wald and Law, in their landmark paper published in BMJ 2003, hypothesized that the use of a fixed-dose combination of statins, β-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin (classic Polypill composition) may increase adherence and decrease CVD by up to 80% when prescribed as primary prevention or in substitution of traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims to describe the available clinical trials performed to assess the impact of fixed-dose combinations on adherence, cost-effectiveness, and the risk factors critical to the onset of CVD. Full article

Acute coronary syndromes (ACS), encompassing conditions like ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndromes (NSTE-ACS), represent a significant challenge in cardiovascular care due to their complex pathophysiology and substantial impact on morbidity and mortality. The 2023 European Society of Cardiology (ESC) guidelines for ACS management introduce several updates in key areas such as invasive treatment timing in NSTE-ACS, pre-treatment strategies, approaches to multivessel disease, and the use of imaging modalities including computed tomography (CT) coronary angiography, magnetic resonance imaging (MRI), and intracoronary imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS). They also address a modulation of antiplatelet therapy, taking into consideration different patient risk profiles, and introduce new recommendations for low-dose colchicine. These guidelines provide important evidence-based updates in practice, reflecting an evolution in the understanding and management of ACS, yet some potentially missed opportunities for more personalized care and technology adoption are discussed. Full article

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes. Full article

Although various guidelines for cardiovascular disease prevention have been established, the optimal drug therapy is often not implemented due to poor medication adherence and the clinical inertia of healthcare practitioners. Polypill strategies are one solution to this problem. Previous studies have established the usefulness of polypills, i.e., combination tablets including three or more medications, for the prevention of cardiovascular disease. For this purpose, the polypills generally contain an antiplatelet medication, an antihypertensive medication, and a statin. For the specific management of hypertension, combination therapy including more than two classes of antihypertensive medications is recommended by most international guidelines. Combination tablets including two classes of antihypertensive medications, such as renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) and Ca-channel blockers or thiazide diuretics, have been reported to be useful for cardiovascular disease prevention and lowering blood pressure (BP) levels. The use of RAS inhibitors is recommended for a wide range of complications, including diabetes, chronic heart failure, and chronic kidney disease. The combination of an RAS inhibitor and diuretic or Ca-channel blocker is thus recommended for the management of hypertension. Finally, we expect that novel medications such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2i), which have a more diverse range of effects in hypertension, heart failure, or diabetes, may be a solution to the problem of polypharmacy. Evidence is accumulating on the benefits of polypill strategies in cardiovascular disease prevention. Combination tablets are also effective for the treatment of hypertension. Full article

The low bioavailability of orally administered drugs as a result of the instability in the gastrointestinal tract environment creates significant challenges to developing site-targeted drug delivery systems. This study proposes a novel hydrogel drug carrier using pH-responsive materials assisted with semi-solid extrusion 3D printing technology, enabling site-targeted drug release and customisation of temporal release profiles. The effects of material parameters on the pH-responsive behaviours of printed tablets were analysed thoroughly by investigating the swelling properties under both artificial gastric and intestinal fluids. It has been shown that high swelling rates at either acidic or alkaline conditions can be achieved by adjusting the mass ratio between sodium alginate and carboxymethyl chitosan, enabling site-targeted release. The drug release experiments reveal that gastric drug release can be achieved with a mass ratio of 1:3, whilst a ratio of 3:1 allows for intestinal release. Furthermore, controlled release is realised by tuning the infill density of the printing process. The method proposed in this study can not only significantly improve the bioavailability of oral drugs, but also offer the potential that each component of a compound drug tablet can be released in a controlled manner at a target location. Full article

This interdisciplinary review focuses on how flexible three-dimensional printing (3DP) technology can aid patients with neurological diseases. It covers a wide variety of current and possible applications ranging from neurosurgery to customizable polypill along with a brief description of the various 3DP techniques. The article goes into detail about how 3DP technology can aid delicate neurosurgical planning and its consequent outcome for patients. It also covers areas such as how the 3DP model can be utilized in patient counseling along with designing specific implants involved in cranioplasty and customization of a specialized instrument such as 3DP optogenetic probes. Furthermore, the review includes how a 3DP nasal cast can contribute to the development of nose-to-brain drug delivery along with looking into how bioprinting could be used for regenerating nerves and how 3D-printed drugs could offer practical benefits to patients suffering from neurological diseases via polypill. Full article

A new universal HPLC-DAD method has been developed for the separation and simultaneous determination of thirteen active pharmaceutical ingredients (APIs): ramipril, lisinopril, enalapril; atenolol, metoprolol; losartan, candesartan; rosuvastatin, atorvastatin, simvastatin; amlodipine; hydrochlorothiazide, acetylsalicylic acid in polypills used in the treatment of hypertension. The chromatographic analysis of the APIs was performed on an ACE-5 C18-PFP column (250 mm × 4.6 mm, 5 μm) with 0.01 M phosphate buffer (pH = 2.50) and acetonitrile in gradient elution as the mobile phase at a flow rate 1.0 mL min⁻¹. UV detection was performed at 230 nm. The analysis time was 35 min. The elaborated method meets the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision for all examined substances. The linearity range was observed in a wide concentration range, whereas the determination coefficients (R²) for the linear model were greater than 0.990. The sensitivity of the method was good with the LOD and LOQ values ranged from 0.0009 to 0.0923 mg mL⁻¹ and from 0.0027 to 0.2794 mg mL⁻¹, respectively. The proposed method showed good precision with RSD less than 1.91% and the accuracy expressed as percent recovery was from 95.20% to 104.62%. The proposed HPLC-DAD method was successfully applied to determine APIs in prepared model mixtures corresponding to the commercially available polypill tablets. The obtained results of the measured contents were with good accuracy (95.84–103.92%) and high precision (RSD < 0.95%) indicating the applicability of the proposed method for the simultaneous determination of the polypill components. Therefore, the method can be an effective tool in the quality control of polypills. Full article

Objective: In Lithuania, no comprehensive national research on statin utilization and trends has yet been undertaken. Nonetheless, this knowledge is critical for the healthcare system to identify key areas for development. We aimed to analyze trends in statin utilization in Lithuania from the past 12 years considering changes in reimbursement policies and the publication of updated international CVD prevention guidelines. Methods: We performed a retrospective, descriptive study of statin utilization in Lithuania from 2010 to 2021. The data were obtained from PharmaZOOM LT, an independent software supplier with nationwide coverage on pharmaceutical market data. The data coverage was 95%. We used anatomical therapeutic chemical (ATC) classification for data extraction and calculated defined daily doses (DDDs) according to the ATC/DDD Toolkit of World Health Organization according to statin dose in a pill. Results: Statin use increased overall from 8.28 DDD/TID in 2010 to 96.06 DDD/TID in 2021. The annual growth rate in sales of statin DDD/TID was 22.28%. The increase was mostly due to the increase in moderate- and high-intensity statins. The increases coincided with changes in reimbursement policy or the publication of international guidelines. Polypill use in Lithuania began steadily increasing after 2016 and reached 19.37% of the total DDD/TID of statins in 2021. Conclusions: The use of statins has increased dramatically in Lithuania over the last decade. Changes in statin reimbursement regulations in the country, as well as worldwide cardiovascular preventive recommendations aiming at lower LDL-C objectives, fueled the progress. Full article

An inaugural study was performed to understand the perceptions of healthcare professionals toward the potential benefits of 3D printing in Singapore. This study sought to increase awareness of 3D printing applications for viable clinical applications and to elucidate the current gaps in therapy where 3D printing could play a role. A common example would be the use of 3D printing to manufacture polypills, thereby reducing the daily pill burden of patients and possibly improving medication adherence. A qualitative descriptive survey with a single-centered cross-sectional design was performed at Tan Tock Seng Hospital, a tertiary referral hospital with 1700 beds. This study had a total of 55 respondents comprising doctors and pharmacists. Most of the respondents viewed the 3D printing of oral dosage forms favorably and agreed about the potential advantages this technology could offer. More than 60% of the respondents were also willing to prescribe 3D printed tablets to patients. Respondents’ concerns were grouped into three main categories: formulation considerations, manufacturing processes, and administrative issues. Viewed in its entirety, this study provides a valuable starting point for understanding the perceptions of healthcare professionals in adopting 3D printing technology. Full article