FORMULATION AND EVALUATION OF MELOXICAM LIQUISOLID COMPACT

Objective: The aim of the present research was to improve dissolution of poorly soluble meloxicam a BCS (Biopharmaceutical Classification System) Class-II drug by utilizing liquisolid technique. Different liquisolid (LS) compacts were prepared using a mathematical model to calculate the required quantities of powder and liquid ingredients to produce acceptably flow able and compressible admixture. Methods: Liquisolid compact was prepared from; microcrystalline cellulose (Avicel PH 102) as carrier, colloidal silicon dioxide (Aerosil 200) and silica (cab-O-sil) as coating material, sodium starch glycol ate and cross povidon as super disintegrants, PVP-K25 and HPMC E5 as additives to increase loading capacity, polyethylene glycol 400, propylene glycol and tween 80 as liquid vehicles. The ratio of carrier to coating material was kept constant in all formulations at 25:1, this ratio was chosen after testing the ratios 5:1, 10:1, 15:1, 20:1 and 25:1. The ratio 25;1 give optimal results relative to other ratios. The prepared LS compacts were evaluated for their tab letting properties. Fourier transform infrared (FTIR) analysis, differential scanning calorimetry (DSC), scanning electron microscope (SEM) and X-ray powder diffraction (XRPD) were performed. Results: The tab letting properties of the liquisolid compacts was within the acceptable limits. The drug release rates of the selected formulas (LS-3, LS-3A, LS-3AP and LS-3AH) of prepared liquisolid compacts were distinctly higher as compared to directly compressed tablets, and marketed tablets. The DSC, XRPD and SEM were suggested loss of meloxicam crystallinity upon liquisolid preparation indicating that even though the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which may be contributed to the enhanced drug dissolution properties. The FTIR spectra showed disappearance of the characteristic absorption band of meloxicam (3290 cm-1) in liquidsolid formulation which might be attributed to the formation of hydrogen bonding between the drug and liquid vehicle; this resulted in drug dissolution enhancement. Conclusion: From this study it concludes that the LS technique is an effective approach to enhance the dissolution rate of meloxicam

Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

published_or_final_versio

Critical values of facet joint angulation and tropism in the development of lumbar degenerative spondylolisthesis: an international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

published_or_final_versio

Differential medication overuse risk of novel anti-migraine therapeutics

Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.</p

Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model

INTRODUCTION: Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model. METHODS: A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon. RESULTS: DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P \u3c 0.001). DISCUSSION/CONCLUSION: Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option

Engagement of early career researchers in collaborative assessments of IPCC reports: achievements and insights

The participation of a diverse –in terms of geography, discipline and gender– group of Early Career Researchers (ECRs) in the peer review process can help alleviate the workload of senior researchers and counteract the perceptual biases that the latter tend to show. Moreover, ECRs can benefit from developing skills that are often not included in educational programs. From 2018 to 2021, the Association of Polar Early Career Scientists, in collaboration with other associations, organized six group reviews of the Intergovernmental Panel on Climate Change (IPCC) reports by a total of more than 600 ECRs from over 70 different countries. This study aims to evaluate this group review in terms of its contribution to the production of scientific knowledge, and as a career development opportunity for ECRs. The data analyzed consists of application forms, review comments, and feedback surveys that were collected during each review process. The results of this study show that, overall, the group reviews were a success in terms of the experience of ECRs and their contribution to the peer review of the IPCC reports. Most survey respondents considered the general organization of the group reviews satisfactory and expressed interest in participating in future group reviews. However, most participants did not engage in discussions with their peers, which constitutes a missed opportunity to engage in active learning and the shared production of knowledge. ECRs made a significant contribution to the review of the IPCC reports by producing an average of 2,422 ± 532 comments per group review, 36% of which were substantive. PhD students were shown to be as proficient reviewers as postdoctoral researchers and faculty reviewers. More importantly, the diversity of reviewers in terms of geography and discipline, together with the fact that they are ECRs, can help produce more balanced scientific reports since they bring new perspectives, thus counteracting the biases that senior researchers have. These group reviews could be improved by providing more comprehensive training and facilitating communication among reviewers so that they can engage in meaningful exchanges. We conclude that the IPCC should formalize the inclusion of ECRs in future reviews of the IPCC reports

Incidência do near miss materno no parto e pós-parto hospitalar: dados da pesquisa Nascer no Brasil

Este estudo avaliou os dados sobre a incidência do near miss materno, identificados segundo os critérios da Organização Mundial da Saúde, na pesquisa Nascer no Brasil. O estudo foi realizado entre fevereiro/2011 e outubro/2012 e os resultados apresentados são estimativas para a população estudada (2.337.476 partos), baseados na amostra de 23.894 puérperas entrevistadas. Os resultados mostraram uma incidência de near miss materno de 10,21 por mil nascidos vivos e uma razão de mortalidade do near miss materno de 30,8 casos para cada morte materna. Os critérios clínicos para identificação do near miss materno foram os mais prevalentes e tiveram incidência de 5,2 por mil nascidos vivos. O near miss materno esteve associado com a idade materna de 35 anos ou mais (RR = 1,6; IC95%: 1,1-2,5), com história de cesariana anterior (RR = 1,9; IC95%: 1,1-3,4) e gestação de risco (RR = 4,5; IC95%: 2,8-7,0). Os hospitais localizados nas capitais (RR = 2,2; IC95%: 1,3-3,8) e os pertencentes ao SUS (RR = 3,2; IC95%: 1,6-6,6) também apresentaram maior incidência de casos de near miss materno. A qualificação dos serviços de assistência ao parto pode ajudar a reduzir a mortalidade materna no Brasil

Nanomedicines for cancer therapy: current status, challenges and future prospects

The emergence of nanomedicine as an innovative and promising alternative technology shows many advantages over conventional cancer therapies and provides new opportunities for early detection, improved treatment, and diagnosis of cancer. Despite the cancer nanomedicines' capability of delivering chemotherapeutic agents while providing lower systemic toxicity, it is paramount to consider the cancer complexity and dynamics for bridging the translational bench-to-bedside gap. It is important to conduct appropriate investigations for exploiting the tumor microenvironment, and achieving a more comprehensive understanding of the fundamental biological processes in cancer and their roles in modulating nanoparticle-protein interactions, blood circulation, and tumor penetration. This review provides an overview of the current cancer nanomedicines, the major challenges, and the future opportunities in this research area