Acta Pharmaceutica最新文献

In patients with chronic heart failure (CHF), the use of angiotensin-converting enzyme inhibitors, including ramipril, is recommended to reduce the risk of heart failure worsening, hospitalisation, and death. Our aim was to investigate the influence of body composition on the pharmacokinetics of ramipril and its active metabolite ramiprilat and to evaluate the changes in pharmacokinetics after prolonged therapy. Twenty-three patients with CHF who were on regular therapy with ramipril participated at the first study visit ( median age 77 years, 65 % male, and 70 % New York Heart Association Class II); 19 patients attended the second study visit and the median time between the two visits was 8 months. Pharmacokinetics were assessed using a nonlinear mixed-effects parent-metabolite model comprising two compartments for ramipril and one compartment for ramiprilat. The influence of body size and composition was best described by an allometric relationship with fat-free mass. In addition, ramipril clearance was related to patient age and daily ramipril dose, while clearance of ramiprilat was influenced by glome rular filtration rate and daily ramipril dose. There were no clinically relevant changes in the pharmacokinetics of ramipril and ramiprilat between the study visits. Due to the relatively stable pharmacokinetics of ramipril, regular outpatient visits at 6-month intervals seem appropriate to evaluate ramipril therapy.

This study investigates the 10-year trend in the sedative and anticholinergic burden among older adults in Slovenia, with the aim of identifying opportunities to optimize pharmacotherapy in this population. A retrospective drug utilization analysis was conducted based on a national anonymized database of dispensed prescriptions from 2009 to 2019. The study employed the sedative load model and the anticholinergic cognitive burden scale to assess the sedative and anti cholinergic burden, respectively. The findings indicate that in 2019, 45.6 % and 40.8 % of older adults (≥ 65 years) used sedative and anticholinergic medications, respectively. A high sedative load and a clinically significant anticholinergic burden were observed in a considerable proportion of older adults (13.2 % and 11.2 %, respectively, in 2019). The age-standardized prevalence of sedative load and anti-cholinergic burden significantly decreased over the 10-year study period by 5.6 % and 1.7 %, respectively (absolute difference), while the prevalence of clinically significant anticholinergic burden remained stable. Notably, the age groups 85-89 years and above 90 years had an increase in the proportion of individuals with a clinically significant anticholinergic burden over the years. These results emphasize the need for targeted interventions, particularly in the oldest age groups, to promote safe and effective medication use among older adults.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.

Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.

At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, i.e., bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.

Remifentanil is an ultra-short-acting synthetic opioid-class analgesic which might be increasingly used "off-label" as pain management during labour. Side effects in parturients during labour, and in the infant at birth are of particular concern, especially respiratory depression which is concentration-dependent, and can occur at levels as low as 3-5 ng mL^-1. The safety of such use, particularly in newborns due to remifentanil placental transfer, has not been fully demonstrated yet, partly due to the lack of a suitable non-invasive analytical method. The aim of our work was to develop a sensitive method to monitor the levels of remifentanil in neonates by a non-invasive sampling of umbi lical cord blood to support efficacy and safety trials. The presented LC-MS method is sensitive enough to reliably quantify remifentanil in just 20 µL of blood at only 0.3 ng mL^-1. The dried blood spot sample preparation included solvent extraction with subsequent solid-phase extraction. The method was validated in terms of accuracy, precision, recovery, matrix effect, and stability, and was successfully applied to a small pilot study. The estimated arterial blood concentrations at the time of delivery ranged from 0.2 to 0.3, and up to 0.9 ng mL^-1 in neonatal, and maternal samples, respectively.

The principal function of skin is to form an effective barrier between the human body and its environment. Impaired barrier function represents a precondition for the development of skin diseases such as atopic dermatitis (AD), which is the most common inflammatory skin disease characterized by skin barrier dysfunction. AD significantly affects patients' quality of life, thus, there is a growing interest in the development of novel delivery systems that would improve therapeutic outcomes. Herein, eight novel lyotropic liquid crystals (LCCs) were investigated for the first time in a double-blind, interventional, before-after, single-group trial with healthy adult subjects and a twice-daily application regimen. LCCs consisted of constituents with skin regenerative properties and exhibited lamellar micro-structure, especially suitable for dermal application. The short- and long-term effects of LCCs on TEWL, SC hydration, erythema index, melanin index, and tolerability were determined and compared with baseline. LCCs with the highest oil content and lecithin/Tween 80 mixture stood out by providing a remarkable 2-fold reduction in TEWL values and showing the most distinctive decrease in skin erythema levels in both the short- and long-term exposure. Therefore, they exhibit great potential for clinical use as novel delivery systems for AD treatment, capable of repairing skin barrier function.

This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.