In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets.

Three-dimensional (3D) printing is quickly being adopted in pharmaceutics due to the many advantages it offers, including treatment, adaptability, the reduction in waste and the accelerated development of new formulations. In this study, micro-extrusion printing was implemented for the production of modified-release hydrocortisone (HCT) mini-tablets for paediatric patients. For the developed formulations, Gelucire® 44/14 and Precirol® ATO 5 were used as the main inks at three different ratios: 70%/30%, 60%/40% and 50%/50%, respectively. The printing parameters (temperature and pressure) were altered accordingly for each ratio to achieve printability. The printed mini-tablets exhibited excellent printing quality, featuring consistent layer thicknesses and smooth surfaces. Dissolution tests were performed, and the results indicated a successful modified release of HCT from the mini-tablets. In summary, micro-extrusion exhibited favourable processing abilities for powder blends, facilitating quick printing and the fabrication of potential personalized dosages.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey.

Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.

Coupling of Fused Deposition Modeling and Inkjet Printing to Produce Drug Loaded 3D Printed Tablets.

In the current study, we have coupled Fused Deposition Modelling (FDM) for the fabrication of plain polyvinyl alcohol (PVA) tablets followed by dispensing of minoxidil ethanolic solutions using inkjet printing. The use of a drop-on-solid printing approach facilitates an accurate and reproducible process while it controls the deposition of the drug amounts. For the purpose of the study, the effect of the solvent was investigated and minoxidil ink solutions of ethanol 70% v/v (P70) or absolute ethanol (P100) were applied on the plain PVA tablets. Physicochemical characterization showed that solvent miscibility with the polymer substrate plays a key role and can lead to the formation of drug crystals on the surface or drug absorption in the polymer matrix. The produced minoxidil tablets showed sustained release profiles or initial bursts strongly affected by the solvent grade used for dispensing the required dose on drug loaded 3D printed tablets. This paradigm demonstrates that the coupling of FDM and inkjet printing technologies could be used for rapid development of personalized dosage forms.

Assessment of a Novel Vitamin D3 Formulation with Nanostructured Lipid Carriers for Transdermal Delivery.

OBJECTIVE: Develop and assess a transdermal emulsion loaded with nanostructured lipid carriers for vitamin D3 supplementation. METHODS: Vitamin D3 loaded nanostructured lipid carriers, produced via high shear homogenization and ultrasonication, were assessed for their particle size, distribution, morphology, zeta potential, entrapment efficiency, and cytotoxicity. They were incorporated into a transdermal vehicle, and the stability and ex vivo permeation were evaluated. RESULTS: Spherical nanoparticles were developed with a particle size of 192.5 nm, a polydispersity index of 0.13, a zeta potential of -29.0 mV, and an entrapment efficiency of 99.75%. They were stable (particle size and distribution) for 15 days when stored in a refrigerator, and for 30 days at room temperature and 32°C. The nanoparticles decreased the drug cytotoxicity against fibroblasts, as shown by IC50 (nanoparticle: 32.48 µg mL-1 vitamin D3: 16.73 µg mL-1). The emulsion loaded with nanoparticles minimized the degradation of vitamin D3 when compared with the nanoparticle dispersion. Additionally, the emulsion provided the skin permeation of vitamin D3 following the recommended daily allowance. CONCLUSION: To the best of our knowledge, this is the first study to use nanostructured lipid carriers for transdermal delivery of vitamin D. The developed formulation is a promising strategy to overcome the vitamin D3 variable oral bioavailability. It also represents a comfortable route of administration; thus it could be beneficial for patients and clinicians. However, further studies are needed to allow the permeation of larger amounts of vitamin D3, and the combination of these nanoparticles with microneedles would be interesting.

Aplicações da manufatura aditiva em oftalmologia / Applications of additive manufacturing in ophthalmology

RESUMO A manufatura aditiva, mais popularmente conhecida como impressão tridimensional, baseia-se no desenvolvimento de um objeto com a ajuda de um software de desenho assistido por computador seguido de sua impressão por meio da deposição de uma matéria-prima, camada por camada, para a construção do produto desejado. Existem vários tipos de técnicas de impressão tridimensional, e o tipo de processo de impressão escolhido depende da aplicação específica do objeto a ser desenvolvido, dos materiais a serem utilizados e da resolução necessária à impressão do produto final. A impressão tridimensional abriu perspectivas na pesquisa e revolucionou o campo das ciências da saúde, com a possibilidade de criação e de desenvolvimento de produtos personalizados de maneira rápida, econômica e de forma mais centralizada do que no processo de manufatura tradicional. As tecnologias de manufatura aditiva remodelaram os diagnósticos médicos; as medidas preventivas e pré-operatórias; o tratamento e a reabilitação, assim como os processos de engenharia de tecidos nos últimos anos. Na oftalmologia, as aplicações da impressão tridimensional são extensas. Modelos anatômicos para aplicação na área da educação e planejamentos cirúrgicos, desenvolvimento de implantes, lentes, equipamentos para diagnósticos, novas aplicações terapêuticas e desenvolvimento de tecidos oculares já estão em desenvolvimento. Por possuir um campo amplo e ser alvo de pesquisa constante, a área oftalmológica permite que a manufatura aditiva ainda seja amplamente utilizada a favor dos médicos e dos pacientes.

ABSTRACT Additive manufacturing, more popularly known as three-dimensional (3D) printing, is based on the development of an object with the help of computer-aided design software followed by its printing through the deposition of a material, layer by layer, to create the desired product. There are several types of 3D printing techniques and the type of printing process chosen depends on the specific application of the object to be developed, the materials to be used, and the resolution required to print the final product. 3D printing has brought new perspectives to research and revolutionized the field of health sciences, with the possibility of creating and developing customized products in a faster, more economical, and more centralized way than in the traditional manufacturing process. Additive manufacturing technologies have reformulated medical diagnostics, preventive, preoperative, treatment, and rehabilitation, as well as tissue engineering processes in recent years. In ophthalmology, the applications of 3D printing are extensive. Anatomical models for application in education and surgical planning, development of implants, lenses, diagnostic equipment, new therapeutic applications, and development of ocular tissues (3D bioprinting) are already under development. As it has a wide field and is the subject of constant research, the ophthalmic area allows additive manufacturing to still be widely used in favor of doctors and patients.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study.

BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.

Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study

ABSTRACT BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVE: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.

Citral Inhibits the Inflammatory Response and Hyperalgesia in Mice: The Role of TLR4, TLR2/Dectin-1, and CB2 Cannabinoid Receptor/ATP-Sensitive K+ Channel Pathways.

Citral ((2E)-3,7-dimethylocta-2,6-dienal), a bioactive component of lemongrass, inhibits oxidant activity, nuclear factor kappa B (NF-κB) activation, and cyclooxygenase-2 (COX-2) expression, even as it activates peroxisome proliferator-activated receptor (PPAR)-α and γ. Additionally, citral produces long-lasting inhibition of transient receptor potential (TRP) channels that are found in sensory neurons, such as TRPV1-3 and TRPM8, while it transiently blocks TRPV4 and TRPA1. Here, the effect of citral in experimental models of acute inflammation and hyperalgesia in mice, and the underlying citral mechanisms of action were investigated. ADMET properties and molecular targets were predicted using the online server. The immunomodulatory and antihyperalgesic effects of citral were evaluated, using mechanical and thermal stimuli, at different time-points on carrageenan, lipopolysaccharides (LPS), and zymosan-induced paw edema and hyperalgesia in mice. ADMET analysis ensures that the citral has not violated Lipinski's rule of five, indicating its safety consumption, and molecular target prediction software identified that citral is a potential fatty acid amide hydrolase (FAAH) inhibitor. Oral treatment with citral (50-300 mg/kg) significantly inhibited carrageenan-induced paw edema and thermal allodynia. Furthermore, citral modulated the inflammation induced by LPS and zymosan, toll-like receptor (TLR) 4, and TLR2/dectin-1 ligands, respectively. Moreover, pretreatment with cannabinoid receptor type 2 (CB2R) antagonists and ATP-sensitive K+ channel inhibitor, but not with a cannabinoid receptor type 1 (CB1R) antagonist, significantly reversed the anti-inflammatory effect of citral. Intriguingly, citral did not cause any relevant action in the central nervous system, and it was safe when assessed in a 14 day toxicity assay in male mice. Therefore, citral constitutes a promising, innovative, and safe molecule for the management of immunoinflammatory conditions and pain states.

Permeation Efficacy of a Transdermal Vehicle with Steroidal Hormones and Nonsteroidal Anti-inflammatory Agents as Model Drugs.

BACKGROUND: Transdermal delivery is an alternative route for the administration of drugs. However, it requires the development of vehicles that allow the drugs to cross the layers of the skin and reach the systemic circulation. OBJECTIVE: In this study, a new transdermal vehicle was evaluated using progesterone, estradiol, estradiol + estriol (Biest) and ketoprofen administered as model drugs. METHODS: To evaluate the ex vivo permeation of the drugs, the Franz vertical diffusion cell with human skin was used. RESULTS: After 24 h, the vehicle was able to deliver 18.32 µg/cm2 of progesterone and 92.07 µg/cm2 of ketoprofen through the skin to the receptor medium. The permeation percentages were 91%, 78.8%, 48.5%, 73.2%, and 63.6%, respectively, for estradiol, estradiol (Biest), estriol (Biest), progesterone and ketoprofen. For all drugs, sufficient amounts were delivered to achieve a systemic effect, and it was also possible to decrease the amount of emulsion applied. CONCLUSION: Thus, the vehicle demonstrated a high performance and the possibility of it being used for drugs that present difficulties in regards to administration by the transdermal route.

A mulher: um sintoma para o homem? / The woman, a man’s symptom? / La femme, symptôme de l’homme? / La mujer: ¿un sintoma para el hombre?

Na última década de seu ensino, Jacques Lacan propõe que uma mulher pode ser um sintoma para um homem. Este artigo revê uma abordagem da teoria freudiana da identificação de gêneros para discutir a proposta de Lacan.

Jacques Lacan suggested that the woman could be man's symptom in the last decade of his teaching. This article proposes to survey some of the Freudian theory of gender identification to discuss Lacan’s hypothesis.

Au cours de la dernière décennie de ses enseignements, Jacques Lacan a suggéré que la femme pourrait être un symptôme de l'homme. Cet article propose la révision d'une approche de la théorie freudienne sur l'identification de gendres pour pouvoir mettre en discussion la proposition de Lacan.

En su última década de enseñanza, Jacques Lacan sostiene que una mujer puede ser un síntoma para un hombre. Este artículo revisa la aproximación de la teoría freudiana de la identificación de géneros para discutir la propuesta de Lacan.

A mulher: um sintoma para o homem? / The woman, a man’s symptom? / La femme, symptôme de l’homme? / La mujer: ¿un sintoma para el hombre?

Na última década de seu ensino, Jacques Lacan propõe que uma mulher pode ser um sintoma para um homem. Este artigo revê uma abordagem da teoria freudiana da identificação de gêneros para discutir a proposta de Lacan.(AU)

Jacques Lacan suggested that the woman could be man's symptom in the last decade of his teaching. This article proposes to survey some of the Freudian theory of gender identification to discuss Lacan’s hypothesis.(AU)

Au cours de la dernière décennie de ses enseignements, Jacques Lacan a suggéré que la femme pourrait être un symptôme de l'homme. Cet article propose la révision d'une approche de la théorie freudienne sur l'identification de gendres pour pouvoir mettre en discussion la proposition de Lacan.(AU)

En su última década de enseñanza, Jacques Lacan sostiene que una mujer puede ser un síntoma para un hombre. Este artículo revisa la aproximación de la teoría freudiana de la identificación de géneros para discutir la propuesta de Lacan.(AU)