Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug's dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.
Polyethylene Glycols , Printing, Three-Dimensional , Technology, Pharmaceutical , Pharmaceutical Preparations , Solubility , Drug Liberation , Drug Compounding , Technology, Pharmaceutical/methods , Tablets
In this study, we introduce an electrochemical doping strategy aimed at manipulating the structure and composition of electrically conductive metal-organic frameworks (c-MOFs). Our methodology is exemplified through a representative c-MOF, Ni3(HITP)2 (HITP=2, 3, 6, 7, 10, 11-hexaiminotriphenylene), synthesized into porous thin films supported by nanocellulose. While the c-MOF exhibits characteristic capacitive behavior in neutral electrolyte; it manifests redox behaviors in both acidic and alkaline electrolytes. Evidence indicates that the organic ligands within c-MOF undergo oxidation (p-doping) and reduction (n-doping) when exposed to specific electrochemical potentials in acidic and alkaline electrolyte, respectively. Interestingly, the p-doping process proves reversible, with the c-MOF structure remaining stable across cyclic p-doping/de-doping. In contrast, the n-doping is irreversible, leading to the gradual decomposition of the framework into inorganic species over a few cycles. Drawing on these findings, we showcase the versatile electrochemical applications of c-MOFs and their derived composites, encompassing electrochemical energy storage, electrocatalysis, and ultrafast actuation. This study provides profound insights into the doping of c-MOFs, offering a new avenue for modulating their chemical and electronic structure, thereby broadening their potential for diverse electrochemical applications.
A wide array of carbon materials finds extensive utility across various industrial applications today. Nonetheless, the production processes for these materials continue to entail elevated temperatures, necessitate the use of inert atmospheres, and often involve the handling of aggressive and toxic chemicals. The prevalent method for large-scale carbon material production, namely the pyrolysis of waste biomass and polymers, typically unfolds within the temperature range of 500-700 °C under a nitrogen (N2 ) atmosphere. Unfortunately, this approach suffers from significant energy inefficiency due to substantial heat loss over extended processing durations. In this work, we propose an interesting alternative: the carbonization of photothermal nanocellulose/polypyrrole composite films through CO2 laser irradiation in the presence of air. This innovative technique offers a swift and energy-efficient means of preparing carbon materials. The unique interaction between nanocellulose and polypyrrole imparts the film with sufficient stability to retain its structural integrity post-carbonization. This breakthrough opens up new avenues for producing binder-free electrodes using a rapid and straightforward approach. Furthermore, the irradiated film demonstrates specific and areal capacitances of 159â F g-1 and 62â µF cm-2 , respectively, when immersed in a 2â M NaOH electrolyte. These values significantly surpass those achieved by current commercial activated carbons. Together, these attributes render CO2 -laser carbonization an environmentally sustainable and ecologically friendly method for carbon material production.
The study presents a streamlined one-step process for producing highly porous, metal-free, N-doped activated carbon (N-AC) for CO2 capture and herbicide removal from simulated industrially polluted and real environmental systems. N-AC was prepared from kraft ligninâa carbon-rich and abundant byproduct of the pulp industry, using nitric acid as the activator and urea as the N-dopant. The reported carbonization process under a nitrogen atmosphere renders a product with a high yield of 30% even at high temperatures up to 800 °C. N-AC exhibited a substantial high N content (4-5%), the presence of aliphatic and phenolic OH groups, and a notable absence of carboxylic groups, as confirmed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Boehm's titration. Porosity analysis indicated that micropores constituted the majority of the pore structure, with 86% of pores having diameters less than 0.6 nm. According to BET adsorption analysis, the developed porous structure of N-AC boasted a substantial specific surface area of 1000 m2 g-1. N-AC proved to be a promising adsorbent for air and water purification. Specifically, N-AC exhibited a strong affinity for CO2, with an adsorption capacity of 1.4 mmol g-1 at 0.15 bar and 20 °C, and it demonstrated the highest selectivity over N2 from the simulated flue gas system (27.3 mmol g-1 for 15:85 v/v CO2/N2 at 20 °C) among all previously reported nitrogen-doped AC materials from kraft lignin. Moreover, N-AC displayed excellent reusability and efficient CO2 release, maintaining an adsorption capacity of 3.1 mmol g-1 (at 1 bar and 25 °C) over 10 consecutive adsorption-desorption cycles, confirming N-AC as a useful material for CO2 storage and utilization. The unique cationic nature of N-AC enhanced the adsorption of herbicides in neutral and weakly basic environments, which is relevant for real waters. It exhibited an impressive adsorption capacity for the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) at 96 ± 6 mg g-1 under pH 6 and 25 °C according to the Langmuir-Freundlich model. Notably, N-AC preserves its high adsorption capacity toward 2,4-D from simulated groundwater and runoff from tomato greenhouse, while performance in real samples from Fyris river in Uppsala, Sweden, causes a decrease of only 4-5%. Owing to the one-step process, high yield, annual abundance of kraft lignin, and use of environmentally friendly activating agents, N-AC has substantial potential for large-scale industrial applications.
INTRODUCTION: Associations between psychiatric disorders and mortality have been extensively studied, but limited evidence exists regarding influence of clinical characteristics on mortality risk, at the time of acute psychiatric hospitalization. METHODS: A prospective total-cohort study included all patients consecutively admitted to Haukeland University Hospital's psychiatric acute ward in Bergen, Norway between 2005 and 2014 (n = 6125). Clinical interviews were conducted at the first admission within the study period, and patients were subsequently followed for up to 15 years in the Norwegian Cause of Death Registry. Competing risks regression models were used to investigate associations between clinical characteristics at first admission and the risk of natural and unnatural death during follow-up. RESULTS: The mean age at first admission and at time of death was 42.5 and 62.8 years, respectively, and the proportion of women in the sample was 47.2%. A total of 1381 deaths were registered during follow-up, of which 65.5% had natural, 30.4% unnatural, and 4.1% unknown causes. Higher age, male sex, unemployment, cognitive deficits, and physical illness were associated with increased risk of natural death. Male sex, having no partner, physical illness, suicide attempts, and excessive use of alcohol and illicit substances were associated with increased risk of unnatural death. CONCLUSION: Psychiatric symptoms, except suicide attempts, were unrelated to increased mortality risk. In the endeavor to reduce the increased mortality risk in people with mental disorders, focus should be on addressing modifiable risk factors linked to physical health and excessive use of alcohol and illicit substances.
Hospitalization , Mental Disorders , Humans , Male , Female , Prospective Studies , Cohort Studies , Cause of Death , Mental Disorders/psychology , Risk Factors
Covalent organic frameworks (COFs) are usually synthesized under solvothermal conditions that require the use of toxic organic solvents, high reaction temperatures, and complicated procedures. Additionally, their insolubility and infusibility present substantial challenges in the processing of COFs. Herein, we report a facile, green approach for the synthesis of imine-linked COFs in an aqueous solution at room temperature. The key behind the synthesis is the regulation of the reaction rate. The preactivation of aldehyde monomers using acetic acid significantly enhances their reactivity in aqueous solutions. Meanwhile, the still somewhat lower imine formation rate and higher imine breaking rates in aqueous solution, in contrast to conventional solvothermal synthesis, allow for the modulation of the reaction equilibrium and the crystallization of the products. As a result, highly crystalline COFs with large surface areas can be formed in relatively high yields in a few minutes. In total, 16 COFs are successfully synthesized from monomers with different molecular sizes, geometries, pendant groups, and core structures, demonstrating the versatility of this approach. Notably, this method works well on the gram scale synthesis of COFs. Furthermore, the aqueous synthesis facilitates the interfacial growth of COF nanolayers on the surface of cellulose nanofibers (CNFs). The resulting CNF@COF hybrid nanofibers can be easily processed into freestanding nanopapers, demonstrating high efficiency in removing trace amounts of antibiotics from wastewater. This study provides a route to the green synthesis and processing of various COFs, paving the way for practical applications in diverse fields.
Recent years have seen an increasing interest in molecular electrocatalysts for the hydrogen evolution reaction (HER). Efficient hydrogen evolution would play an important role in a sustainable fuel economy, and molecular systems could serve as highly specific and tunable alternatives to traditional noble metal surface catalysts. However, molecular catalysts are currently mostly used in homogeneous setups, where quantitative evaluation of catalytic activity is non-standardized and cumbersome, in particular for multistep, multielectron processes. The molecular design community would therefore be well served by a straightforward model for prediction and comparison of the efficiency of molecular catalysts. Recent developments in this area include attempts at applying the Sabatier principle and the volcano plot concept - popular tools for comparing metal surface catalysts - to molecular catalysis. In this work, we evaluate the predictive power of these tools in the context of experimental operating conditions, by applying them to a series of tetraphenylporphyrins employed as molecular electrocatalysts of the HER. We show that the binding energy of H and the redox chemistry of the porphyrins depend solely on the electron withdrawing ability of the central metal ion, and that the thermodynamics of the catalytic cycle follow a simple linear free energy relation. We also find that the catalytic efficiency of the porphyrins is almost exclusively determined by reaction kinetics and therefore cannot be explained by thermodynamics alone. We conclude that the Sabatier principle, linear free energy relations and molecular volcano plots are insufficient tools for predicting and comparing activity of molecular catalysts, and that experimentally useful information of catalytic performance can still only be obtained through detailed knowledge of the catalytic pathway for each individual system.
OBJECTIVES: Compulsory mental health care includes compulsory hospitalisation and outpatient commitment with medication treatment without consent. Uncertain evidence of the effects of compulsory care contributes to large geographical variations and a controversy on its use. Some argue that compulsion can rarely be justified and should be reduced to an absolute minimum, while others claim compulsion can more frequently be justified. The limited evidence base has contributed to variations in care that raise issues about the quality/appropriateness of care as well as ethical concerns. To address the question whether compulsory mental health care results in superior, worse or equivalent outcomes for patients, this project will utilise registry-based longitudinal data to examine the effect of compulsory inpatient and outpatient care on multiple outcomes, including suicide and overall mortality; emergency care/injuries; crime and victimisation; and participation in the labour force and welfare dependency. METHODS: By using the natural variation in health providers' preference for compulsory care as a source of quasi-randomisation we will estimate causal effects of compulsory care on short- and long-term trajectories. CONCLUSIONS: This project will provide valuable insights for service providers and policy makers in facilitating high quality clinical care pathways for a high risk population group.
Fused deposition modeling (FDM) and selective laser sintering (SLS) are two of the most employed additive manufacturing (AM) techniques within the pharmaceutical research field. Despite the numerous advantages of different AM methods, their respective drawbacks have yet to be fully addressed, and therefore combinatorial systems are starting to emerge. In the present study, hybrid systems comprising SLS inserts and a two-compartment FDM shell are developed to achieve controlled release of the model drug theophylline. Via the use of SLS a partial amorphization of the drug is demonstrated, which can be advantageous in the case of poorly soluble drugs, and it is shown that sintering parameters can regulate the dosage and release kinetics of the drug from the inserts. Furthermore, via different combinations of inserts within the FDM-printed shell, various drug release patterns, such as a two-step or prolonged release, can be achieved. The study serves as a proof of concept, highlighting the advantages of combining two AM techniques, both to overcome their respective shortcomings and to develop modular and highly tunable drug delivery devices.
Drug Delivery Systems , Theophylline , Pharmaceutical Preparations , Drug Liberation , Drug Delivery Systems/methods , Printing, Three-Dimensional , Technology, Pharmaceutical/methods , Dosage Forms , Tablets
Porous organic polymers (POPs) with high porosity and tunable functionalities have been widely studied for use in gas separation, catalysis, energy conversion and energy storage. However, the high cost of organic monomers, and the use of toxic solvents and high temperatures during synthesis pose obstacles for large-scale production. Herein, we report the synthesis of imine and aminal-linked POPs using inexpensive diamine and dialdehyde monomers in green solvents. Theoretical calculations and control experiments show that using meta-diamines is crucial for forming aminal linkages and branching porous networks from [2+2] polycondensation reactions. The method demonstrates good generality in that 6 POPs were successfully synthesized from different monomers. Additionally, we scaled up the synthesis in ethanol at room temperature, resulting in the production of POPs in sub-kilogram quantities at a relatively low cost. Proof-of-concept studies demonstrate that the POPs can be used as high-performance sorbents for CO2 separation and as porous substrates for efficient heterogeneous catalysis. This method provides an environmentally friendly and cost-effective approach for large-scale synthesis of various POPs.
Additive Manufacturing (AM) is a fast-growing approach to produce personalized oral dosage forms. Even though some AM technologies are promising as alternative to conventional compounding with resulting dosage manipulation, they still suffer from a lack of quality control. Due to the high regulatory demands and standards applied to dosage forms in the case of dose accuracy and tablet properties such as friability, effective quality control is a key feature in promoting AM as a valid technology for patient-tailored medications. One of the AM techniques used is selective laser sintering, which allows for capturing the surface state layer-by-layer during the printing process. It provides the opportunity to apply non-destructive quality control based on image analysis extracting essential data at each layer of the sintering process. This work is devoted to establishing the value of data gathered via thermal image analysis for the subsequent quality control.
Printing, Three-Dimensional , Humans , Quality Control , Precision Medicine
Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing in this study. The tablet batches were prepared using either copovidone (N-vinyl-2-pyrrolidone and vinyl acetate, PVP/VA) or polyvinyl alcohol (PVA) and activated carbon (AC) as radiation absorbent, which was added to improve the sintering of the polymer. The physical properties of the dosage forms were evaluated at different pigment concentrations (i.e., 0.5 and 1.0 wt%) and at different laser energy inputs. The mass, hardness, and friability of the tablets were found to be tunable and structures with greater mass and mechanical strength were obtained with increasing carbon concentration and energy input. Amorphization of the active pharmaceutical ingredient in the drug-loaded batches, containing 10 wt% naproxen and 1 wt% AC, was achieved in-situ during printing. Thus, amorphous solid dispersions were prepared in a single-step process and produced tablets with mass losses below 1 wt%. These findings show how the properties of dosage forms can be tuned by careful selection of the process parameters and the powder formulation. SLS 3D printing can therefore be considered to be an interesting and promising technique for the fabrication of personalized medicines.
Lasers , Polymers , Powders , Drug Compounding/methods , Tablets/chemistry , Polymers/chemistry , Printing, Three-Dimensional , Drug Liberation , Technology, Pharmaceutical/methods , Dosage Forms
The incorporation of drug-loaded mesoporous materials in dosage forms prepared with fused deposition modeling (FDM) has shown the potential to solve challenges relating to additive manufacturing techniques, such as the stability of poorly-soluble drugs in the amorphous state. However, the addition of these non-melting mesoporous materials significantly affects the mechanical properties of the filament used in FDM, which in turn affects the printability of the feedstock material. Therefore, in this study a full-factorial experimental design was utilized to investigate different processing parameters of the hot melt extrusion process, their effect on various mechanical properties and the potential correlation with the filaments' printability. The thermolabile, poorly-soluble drug ibuprofen was utilized as a model drug to assess the potential of two mesoporous materials, Mesoporous Magnesium Carbonate (MMC) and a silica-based material (MCM-41), to thermally protect the loaded drug. Factorial and principal components analysis displayed a correlation between non-printable MCM-41 filaments and their mechanical properties where printable filaments had a maximum stress >7.5 MPa and a Young's modulus >83 MPa. For MMC samples there was no clear correlation, which was in large part attributed to the filaments' inconsistencies and imperfections. Finally, both mesoporous materials displayed a thermal protective feature, as the decomposition due to the thermal degradation of a significant portion of the thermolabile drug was shifted to higher temperatures post-loading. This highlights the potential capability of such a system to be implemented for thermosensitive drugs in FDM applications.
The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.
COVID-19 , Humans , COVID-19 Vaccines , SARS-CoV-2 , Precision Medicine
The development of functional materials from food waste sources and minerals is currently of high importance. In the present work, polylactic acid (PLA)/silica composites were prepared by in situ ring-opening polymerizations of L-lactide onto the surface of pristine (Silochrom) and amine-functionalized (Silochrom-NH2) silica. The characteristics of the ring-opening polymerization onto the surface of modified and unmodified silica were identified and discussed. Fourier transform infrared spectroscopy was used to confirm the polymerization of lactide onto the silica surface, and thermogravimetric analysis determined that PLA constituted 5.9% and 7.5% of the composite mass for Silochrom/PLA and Silochrom-NH2/PLA, respectively. The sorption properties of the composites with respect to Pb(II), Co(II), and Cu(II) ions were investigated, and the effect of contact time, initial metal ion concentration, and initial pH were evaluated. Silochrom-NH2/PLA composites were found to have a higher adsorption capacity than Silochrom/PLA for all chosen ions, with the highest adsorption value occurring for Pb2+ at 1.5 mmol/g (90% removal efficiency). The composites showed the highest performance in the neutral or near-neutral pH (created by distilled water or buffer pH 6.86) during the first 15 min of phase contact. The equilibrium characteristics of adsorption were found to follow the Langmuir isotherm model rather than the Freundlich and Temkin models. Perspective applications for these PLA/silicas include remediation of industrial wastewater or leaching solutions from spent lead-acid and Li-ion batteries.
An attractive approach to increase the aqueous apparent solubility of poorly soluble drugs is to formulate them in their amorphous state. In the present study, celecoxib, a poorly soluble drug, was successfully loaded into mesoporous magnesium carbonate (MMC) in its amorphous state via a solvent evaporation method. Crystallization of celecoxib was suppressed, and no reaction with the carrier was detected. The MMC formulation was evaluated in vitro and in vivo in terms of oral bioavailability. Celebra®, a commercially available formulation, was used as a reference. The two celecoxib formulations were orally administrated in male rats (average of n = 6 animals per group), and blood samples for plasma were taken from all animals at different time points after administration. There was no statistical difference (p > 0.05) in AUCinf between the two formulations. The results showed that MMC may be a promising drug delivery excipient for increasing the bioavailability of compounds with solubility-limited absorption.
Excipients , Administration, Oral , Animals , Biological Availability , Celecoxib/chemistry , Magnesium , Male , Rats , Solubility , Solvents/chemistry
BACKGROUND: Evidence is limited for the associations between use of psychotropic medications and overactive, aggressive, disruptive or agitated behavior (OADA)1 in clinical practice. AIMS: To investigate the associations between risk of readmission with OADA and use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines in patients with schizophrenia. METHOD: A consecutive total cohort diagnosed with schizophrenia (N = 663) after admission to the Haukeland University Hospital psychiatric acute unit in Bergen, Norway, was followed from discharge over a 10-year period. At every following readmission, the level of OADA was assessed using the first item of the Health of the Nation Outcome Scale (HoNOS). Periods of use versus non-use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines were recorded as time-dependent variables in each patient and compared using Cox multiple regression analyses. RESULTS: A total of 161 (24.3 %) patients were readmitted with OADA, and the mean (SD) and median times in years to readmission with OADA were 2.8 (2.6) and 2.1, respectively. We found that the risk of readmission with OADA was negatively associated with use of antipsychotics (adjusted hazard ratio (AHR) = 0.33, p < 0.01, CI: 0.24-0.46) and antidepressants (AHR = 0.57, p = 0.03, CI: 0.34-0.95), positively associated with use of benzodiazepines (AHR = 1.95, p < 0.01, CI: 1.31-2.90) and not significantly associated with use of mood stabilizers. CONCLUSIONS: Use of antipsychotics and antidepressants is associated with reduced risk of readmission with OADA whereas benzodiazepines are associated with an increased risk of readmission with OADA in patients with schizophrenia.
Antipsychotic Agents , Schizophrenia , Humans , Schizophrenia/drug therapy , Schizophrenia/chemically induced , Psychotropic Drugs/adverse effects , Antipsychotic Agents/adverse effects , Benzodiazepines/adverse effects , Antidepressive Agents/therapeutic use , Antimanic Agents , Anticonvulsants
This study presents a molecular surface modification approach to synthesizing a family of silver chalcogenolate clusters (SCCs) containing the same [Ag12S6] core and different surface-bonded organic ligands (DMAc or pyridines; DMAc = dimethylacetamide), with the aim of tuning the luminescence properties and increasing the structural stability of the SCCs. The SCCs displayed strong and tuneable luminescence emissions at 77 K (from green to orange to red) as influenced by the peripheral pyridine ligands. In addition, SCC 5 protected by pyridine molecules was stable in ambient air, humid air and even liquid water for a long time (up to 1 week), and it was more structurally stable than SCC 1 bonded with DMAc molecules under the same conditions. The high structural stability of SCC 5 can be explained by the ability of pyridine molecules to form strong coordination bonds with silver atoms. This study offers a new way of designing structurally stable metal nanoclusters with tuneable physicochemical properties.
PURPOSE: Little is known about the impact of different psychotropic drugs on acute readmission risk, when used concomitantly in a real-life setting. We aimed to investigate the association between acute readmission risk and use of antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines in patients with schizophrenia. METHODS: A cohort study included all patients diagnosed with schizophrenia admitted to a psychiatric acute unit at Haukeland University Hospital in Bergen, Norway, during a 10-year period (N = 663). Patients were followed from discharge until first readmission or censoring. Cox multiple regression analyses were conducted using antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines as time-dependent variables, and periods of use and nonuse were compared within individual patients. Adjustments were made for sex, age at index admission, and excessive use of alcohol and illicit substances. RESULTS: A total of 410 patients (61.8%) were readmitted during follow-up, and the mean and median times in days to readmission were 709 and 575, respectively. Compared with nonuse, the use of antipsychotic drugs was associated with reduced risk of readmission (adjusted hazards ratio, 0.20; P < 0.01; confidence interval, 0.16-0.24), and the use of benzodiazepines was associated with increased risk of readmission (adjusted hazards ratio, 1.51; P < 0.01; confidence interval, 1.13-2.02). However, no relation to readmission risk was found for the use of antidepressants and mood stabilizers. CONCLUSIONS: We found that use of benzodiazepines and antipsychotic drugs are inversely associated with acute readmission risk in schizophrenia.
Antipsychotic Agents/therapeutic use , Benzodiazepines/therapeutic use , Patient Readmission/statistics & numerical data , Schizophrenia/drug therapy , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Antidepressive Agents/therapeutic use , Antimanic Agents/therapeutic use , Female , Follow-Up Studies , Humans , Male , Middle Aged , Proportional Hazards Models , Psychiatric Department, Hospital , Risk , Young Adult
Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.
