Thyroid B-Cell Lymphoma in the Background of Hashimoto's Thyroiditis: A Case Report and Literature Review.

Primary thyroid lymphoma (PTL) is a rare type of thyroid cancer, comprising less than 5% of all thyroid cancer cases. PTL includes subtypes like diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue lymphoma (MALT). The connection between PTL and autoimmune diseases of the thyroid, particularly Hashimoto's thyroiditis, has gained recognition in recent years. Studies have indicated an increased incidence of PTL among individuals with Hashimoto's thyroiditis. However, effectively recognizing and managing PTL in the context of autoimmune thyroid diseases remains challenging. Further research and clinical experience are needed to develop comprehensive strategies for early detection and optimal management of this complex condition. In a case involving an 88-year-old female diagnosed with diffuse large B-cell lymphoma, she presented with a complaint of persistent neck swelling for five years. The patient also experienced symptoms such as dysphagia, hoarseness of voice, obstructive sleep apnea, and choking attacks. Surgical resection of the neck swelling was successfully performed, and the patient was referred to the oncology department for further treatment. Thyroid B-cell lymphoma is an exceedingly rare form of thyroid cancer, typically identified in individuals who have a history of Hashimoto's thyroiditis. The prognosis for thyroid B-cell lymphoma is generally unfavorable, and surgical intervention remains the primary treatment approach for such cases.

Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells.

Purpose: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Methods: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. Results: The developed IVO-PLGA-NPs were evaluated for their particle size (171.7±4.9 nm), PDI (0.333), ZP (-23.0±5.8 mV), EE (96.3±4.3%), and DL (9.66±1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3±5.2 nm), PDI (0.311), ZP +25.9±5.7 mV, EE (90.8±5.7%), and DL (9.42±0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Conclusion: Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.

The Impact of Frequent Glucose Monitoring on the Prevalence of Complications Among Patients With Diabetes in Saudi Arabia.

BACKGROUND: Diabetes mellitus (DM), including type 1 diabetes (T1D) and type 2 diabetes (T2D), affects the absorption of glucose from the blood. DM has serious complications that can be prevented by adequate knowledge of the disease and its complications, a healthy lifestyle, a modified diet, and regular glucose monitoring. Hence, this study aimed to assess the effects of frequent glucose monitoring on the occurrence of DM complications. METHODS: This cross-sectional study was performed at King Abdulaziz University Hospital between June and December 2022 and included patients with T1D or T2D. After consent, participants who agreed to join filled out an online questionnaire that was used to acquire information, such as demographic data, type of diabetes, blood glucose monitoring, and diabetic complications. RESULTS: A total of 206 diabetic patients participated in this study, with a mean age of 41.2±19.37, with 53.4% having T1D. Most participants monitored their glucose levels (85.4%), and the majority (65.3%) monitored them once or more daily. Patients who monitored their glucose levels more frequently had significantly fewer complications (p = 0.002). Continuous glucose monitoring (CGM) was the best monitoring method, as it demonstrated the lowest rate of complications compared to other methods (p = 0.002). CONCLUSIONS: Frequent glucose monitoring and the use of CGM devices were associated with a decreased number of DM complications. Thus, we recommend that physicians encourage patients to perform CGM as it helps increase the frequency of monitoring.

Pesquisacaminhante: a pesquisa ação-participante (PAP) como método de pesquisa longitudinal / Walker research: the Action-Participant Research (PAP) as a longitudinal research method / Investigación walker: la Investigación Acción-Participante (PAP) como método de investigación longitudinal

Este artigo relata uma pesquisa ação-participante longitudinal realizada desde 2016 até 2021 com mulheres indígenas Xokleng/Laklãnõ que vivem no contexto urbano de Blumenau, SC. Analisa a trama afetiva que compôs esta caminhada de seis anos e traça a configuração do método que denominamos de pesquisacaminhante para demarcar a temporalidade e o lugar das pesquisadoras, das pesquisadoras-participantes e sua intencionalidade, de fortalecer a luta e a resistência dessas que vivem na cidade de Blumenau, uma cidade de origem germânica e marcadamente "branca". Como instrumento, foram utilizados entrevistas, fotografias, diversos encontros pela cidade e participação em eventos oficiais e, principalmente, encontros constantes entre as pesquisadoras, nos quais elas puderam se expressar como mulheres indígenas. O referencial teórico é a psicologia sócio-histórica, com base nas reflexões de Vigotski e Spinoza, utilizando o afeto como bússola das ações. O método revelou potência para contribuir com a práxis da psicologia social, destacando aquelas voltadas às comunidades tracionais. (AU)

This article reports a longitudinal participant-action research carried out from 2016 to 2021 with indigenous women Xokleng/Laklãnõ who live in the urban context of Blumenau, SC. Analyzes the affective plot that composed this walk of six years and outlines the configuration of the method we call walking research to demarcate the temporality and the place of researchers, researcher-participants and their intention to strengthen the struggle and resistance those who live in the city of Blumenau, a city of German origin and markedly "white". As instrument, interviews, photographs, various meetings around the city and participation in official events were used. and, mainly, constant meetings between the researchers, in which they could express themselves as women indigenous. The theoretical reference is socio-historical psychology, based on the reflections of Vigotski and Spinoza, using the affection as a compass of actions. The method revealed power to contribute to the practice of social psychology, highlighting those aimed at traditional communities. (AU)

Este artículo reporta una investigación longitudinal de acción participante realizada de 2016 a 2021 con mujeres indígenas Xokleng/Laklãnõ que viven en el contexto urbano de Blumenau, SC. Analiza la trama afectiva que compuso este paseo de seis años y esboza la configuración del método que llamamos walking research para demarcar la temporalidad y el lugar de los investigadores, los investigadores-participantes y su intención de fortalecer la lucha y la resistencia los que viven en a ciudad de Blumenau, ciudad de origen alemán y marcadamente "blanca". Como se utilizó el instrumento, entrevistas, fotografías, diversos encuentros por la ciudad y participación en actos oficiales, y, principalmente, encuentros constantes entre las investigadoras, en las que pudieran expresarse como mujeres indígena. El referente teórico es la psicología sociohistórica, a partir de las reflexiones de Vigotski y Spinoza, utilizando la el afecto como brújula de acciones. El método reveló poder contribuir a la práctica de la psicología social, destacando los destinados a las comunidades tradicionales. (AU)

Association of Vitamin D Deficiency, Dyslipidemia, and Obesity with the Incidence of Coronary Artery Diseases in Type 2 Diabetic Saudi Patients.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is a chronic metabolic disease associated with vascular complications. We aimed to evaluate the relationship of vitamin D deficiency, dyslipidemia, and obesity with the incidence of coronary artery disease in type 2 diabetes mellitus. METHODS: The study included 200 Saudi adult subjects, aged 40 - 60 years, of both genders, attending King Abdulaziz Specialist Hospital in Taif city. Subjects were divided into four groups; 50 subjects each: Control group, type 2 diabetic, type 2 diabetic with coronary artery disease, and type 2 diabetic obese patients having body mass index (BMI) ≥ 30 kg/m2. Serum vitamin D (25-OH-D), fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and glycosylated hemoglobin (HbA1c) levels were estimated. RESULTS: Serum vitamin D and HDL-C in the three diabetic patient groups were significantly decreased (p < 0.001) compared to the control group. Among patient groups, the levels in the diabetic coronary and diabetic obese patients were significantly decreased as compared to the diabetic patient group (p < 0.001). FBG levels, HbA1c%, TC, TG, LDL-C levels, and BMI in all diabetic patient groups were significantly higher (p < 0.001) in comparison to control. Significant negative correlations were observed between serum vitamin D and FBG, HbA1c%, TC, TG, LDL-C levels, and BMI whereas positive correlations with HDL-C in all diabetic patient groups. CONCLUSIONS: The deficiency status of 25-OH-D is associated with dyslipidemia in type 2 Saudi diabetic patients, specifically those complicated with obesity and coronary artery diseases.

Association of Vitamin D Deficiency and Vitamin D Receptor Genetic Variants With Coronary Artery Disease in Type 2 Diabetic Saudi Patients.

BACKGROUND/AIM: Vitamin D deficiency accelerates the onset of type 2 diabetes mellitus (T2DM). Polymorphisms in the vitamin D receptor (VDR) have been linked to coronary artery disease (CAD). This study aimed to evaluate the association of vitamin D deficiency and VDR polymorphism with CAD in T2DM. PATIENTS AND METHODS: A total of 150 adult male and female subjects, aged from 40 to 60 years, were divided into three groups, each with 50 subjects; control group, T2DM, and T2DM with CAD. Fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, glycosylated hemoglobin (HbA1c), and 25-hydroxyvitamin D (25-OH D) were assessed. VDR genotypes (BsmI, Taq1 and FOK1) were investigated by polymerase chain reaction fragment length polymorphism. RESULTS: There was a significant negative correlation between serum 25-OH D and FBG, TC, TG, and LDL-C levels, and a positive correlation with HDL-C levels in all diabetic patient groups. The risk of CAD was markedly higher in the group of T2DM with CAD in comparison to the control (p<0.0001) and the T2DM group. Regarding Taq1, there was also a significantly higher risk of CAD in Tt+tt genotypes and t allele in the T2DM with CAD group compared to control (p<0.001, 0.031 respectively). In addition, 25-OH D concentrations and the prevalence of VDR polymorphisms (BsmI, Taq1) were correlated with the risk of CAD. CONCLUSION: Deficiency of vitamin D and the prevalence of VDR polymorphisms (BsmI, Taq1) can serve as important markers for CAD.

Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients.

BACKGROUND: Vitamin D is a locally acting hormone, which plays a major role in skeletal health. Previous studies reported an important role of vitamin D in modulation of inflammatory response. We aimed to investigate the role of vitamin D deficiency and hypoxia-inducible factor (HIF-1α) as markers for the progression of diabetic nephropathy in Saudi patients with type 2 diabetes mellitus (T2DM). METHODS: We included 174 Saudi patients with T2DM in addition to 60 healthy control subjects. Patients were classified according to urinary Albumin to Creatinine Ratio (ACR) into three groups: Group AI: ACR < 30 µg/mg, Group AII: ACR levels of 30 - 300 µg/mg and Group AIII: ACR > 300 µg/mg. We estimated fasting blood glucose, HbA1c, lipid profile, serum creatinine, hemoglobin concentration (Hb), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, serum 25 hydroxyvitamin D, calcium, parathyroid hormone (PTH), tumor necrosis factor (TNF-α), C- reactive protein (CRP), and hypoxia-inducible factor (HIF-1α). RESULTS: There was a significant difference among studied groups regarding serum levels of vitamin D, calcium, PTH, TNF-α, CRP, and HIF-1α levels. The level of vitamin D was lower in diabetic patients in comparison to the controls and was significantly related to the severity of renal nephropathy as indicated by the level of albumin in urine. Moreover, vitamin D levels showed significant negative correlation with the inflammatory markers: TNF-α, CRP, and HIF-1α levels. CONCLUSIONS: Vitamin D deficiency and elevated HIF-1α serum levels showed a significant correlation to progression of nephropathy in Saudi patients with T2DM.

Effect of Application of Treadmill Training on Metabolic Control and Vitamin D Level in Saudi Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus type 2 and vitamin D deficiency are both prevalent in the Saudi Arabia. Vitamin D deficiency treatment with supplements carries a risk of intoxication. AIM: The present study is aimed at elucidating the effect of exercise on modulation of metabolic status and vitamin D level in patients with type 2 diabetes mellitus (T2DM). METHODS: A sum of 110 type 2 diabetic patients were voluntarily enrolled for the present investigation by dividing them into two separate groups (55 individuals for each group), the diabetic study group and diabetic control group. The diabetic study group was engaged in the training program using treadmill exercise. Laboratory parameters were monitored before and after the training program. RESULTS: There were significant elevation in the diabetic study group compared to diabetic control group regarding postexercise vitamin D level, high-density lipoprotein (HDL) (p value ≤ 0.001, 0.045; respectively). In addition, triglycerides, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1C), and homeostatic model assessment-insulin resistance (HOMA-IR) were significantly decreased (p value < 0.001 for all mentioned parameters). Moreover, there were significant higher level in postexercise parameters as compared to preexercise level in the diabetic study group. CONCLUSION: The exercise training program improved the metabolic control and vitamin D level after three months of intervention.

Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma.

Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the ß-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) (p < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ (p < 0.001) and IL-1ß (p < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer.

Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach.

Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this research, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting the moisture-activated dry granulation (MADG) process. In this method, heating and drying steps were omitted so, called green granulation process. A 32 full-factorial design was performed for optimization of key process variables, namely the granulation fluid level (X1) and the wet massing time (X2). Granulation of CNG was carried out in the presence of polyvinylpyrrolidone, and the prepared granules were compressed into tablets. Regression analysis demonstrated the significant (p ≤ 0.05) effect of X1 and X2 on properties of granules and corresponding tablets, with pronounced impact of X1. Additionally, marked improvement of granules' properties and tableting of CNG were observed. Furthermore, the optimized process conditions that produced good flow properties of granules and acceptable tablets were high level of granulation fluid (3.41% w/w) and short wet massing time (1.0 min). Finally, the MADG process gives the opportunity to ameliorate the poor flow and tableting problems of CNG with lower amounts of excipients, which are important for successful development of uniform dosage unit.

Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles.

PURPOSE: This study evaluated the stereoisomeric effect of L- and D-penetratin-cell-penetrating peptides (CPPs)-incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS). METHODS: Insulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin. RESULTS: The mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and -17.0 to -23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t1/2) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively. CONCLUSION: Penetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration.

Pathoarchitectonics of the cerebral cortex in chorea-acanthocytosis and Huntington's disease.

AIMS: Quantitative estimation of cortical neurone loss in cases with chorea-acanthocytosis (ChAc) and its impact on laminar composition. METHODS: We used unbiased stereological tools to estimate the degree of cortical pathology in serial gallocyanin-stained brain sections through the complete hemispheres of three subjects with genetically verified ChAc and a range of disease durations. We compared these results with our previous data of five Huntington's disease (HD) and five control cases. Pathoarchitectonic changes were exemplarily documented in TE1 of a 61-year-old female HD-, a 60-year-old female control case, and ChAc3. RESULTS: Macroscopically, the cortical volume of our ChAc cases (ChAc1-3) remained close to normal. However, the average number of neurones was reduced by 46% in ChAc and by 33% in HD (P = 0.03 for ChAc & HD vs. controls; P = 0.64 for ChAc vs. HD). Terminal HD cases featured selective laminar neurone loss with pallor of layers III, V and VIa, a high density of small, pale, closely packed radial fibres in deep cortical layers VI and V, shrinkage, and chromophilia of subcortical white matter. In ChAc, pronounced diffuse astrogliosis blurred the laminar borders, thus masking the complete and partial loss of pyramidal cells in layer IIIc and of neurones in layers III, V and VI. CONCLUSION: ChAc is a neurodegenerative disease with distinct cortical neurodegeneration. The hypertrophy of the peripheral neuropil space of minicolumns with coarse vertical striation was characteristic of ChAc. The role of astroglia in the pathogenesis of this disorder remains to be elucidated.

Mixing of low-dose cohesive drug and overcoming of pre-blending step using a new gentle-wing high-shear mixer granulator.

The objective of this study was to examine the influence of drug amount and mixing time on the homogeneity and content uniformity of a low-dose drug formulation during the dry mixing step using a new gentle-wing high-shear mixer. Moreover, the study investigated the influence of drug incorporation mode on the content uniformity of tablets manufactured by different methods. Albuterol sulfate was selected as a model drug and was blended with the other excipients at two different levels, 1% w/w and 5% w/w at impeller speed of 300 rpm and chopper speed of 3000 rpm for 30 min. Utilizing a 1 ml unit side-sampling thief probe, triplicate samples were taken from nine different positions in the mixer bowl at selected time points. Two methods were used for manufacturing of tablets, direct compression and wet granulation. The produced tablets were sampled at the beginning, middle, and end of the compression cycle. An analysis of variance analysis indicated the significant effect (p < .05) of drug amount on the content uniformity of the powder blend and the corresponding tablets. For 1% w/w and 5% w/w formulations, incorporation of the drug in the granulating fluid provided tablets with excellent content uniformity and very low relative standard deviation (∼0.61%) during the whole tableting cycle compared to direct compression and granulation method with dry incorporation mode of the drug. Overall, gentle-wing mixer is a good candidate for mixing of low-dose cohesive drug and provides tablets with acceptable content uniformity with no need for pre-blending step.

Anticancer Efficacy of Self-Nanoemulsifying Drug Delivery System of Sunitinib Malate.

Sunitinib malate (SM) is reported as a weakly soluble drug in water due to its poor dissolution rate and oral bioavailability. Hence, in the current study, various "self-nanoemulsifying drug delivery systems (SNEDDS)" of SM were prepared, characterized and evaluated for the enhancement of its in vitro dissolution rate and anticancer efficacy. On the basis of solubilization potential of SM in various excipients, "Lauroglycol-90 (oil), Triton-X100 (surfactant) and Transcutol-P (cosurfactant)" were selected for the preparation of SM SNEDDS. SM-loaded SNEDDS were developed by spontaneous emulsification method, characterized and evaluated for "thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity index (PDI), zeta potential (ZP), surface morphology, refractive index (RI), the percent of transmittance (% T) and drug release profile." In vitro dissolution rate of SM was significantly enhanced from an optimized SNEDDS in comparison with SM suspension. The optimized SNEDDS of SM with droplet size of 42.3 nm, PDI value of 0.174, ZP value of -36.4 mV, RI value of 1.339, % T value of 97.3%, and drug release profile of 95.4% (after 24 h via dialysis membrane) was selected for in vitro anticancer efficacy in human colon cancer cells (HT-29) by MTT assay. MTT assay indicated significant anticancer efficacy of optimized SM SNEDDS against HT-29 cells in comparison with free SM. The results of this study showed the great potential of SNEDDS in the enhancement of in vitro dissolution rate and anticancer efficacy of poorly soluble drug such as SM.

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.

Preparation and evaluation of enteric coated tablets of hot-melt extruded lansoprazole.

The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for six months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods.

Optimization of hot melt extrusion parameters for sphericity and hardness of polymeric face-cut pellets.

The aim of this study was to formulate face-cut, melt-extruded pellets, and to optimize hot melt process parameters to obtain maximized sphericity and hardness by utilizing Soluplus(®) as a polymeric carrier and carbamazepine (CBZ) as a model drug. Thermal gravimetric analysis (TGA) was used to detect thermal stability of CBZ. The Box-Behnken design for response surface methodology was developed using three factors, processing temperature ( °C), feeding rate (%), and screw speed (rpm), which resulted in 17 experimental runs. The influence of these factors on pellet sphericity and mechanical characteristics was assessed and evaluated for each experimental run. Pellets with optimal sphericity and mechanical properties were chosen for further characterization. This included differential scanning calorimetry, drug release, hardness friability index (HFI), flowability, bulk density, tapped density, Carr's index, and fourier transform infrared radiation (FTIR) spectroscopy. TGA data showed no drug degradation upon heating to 190 °C. Hot melt extrusion processing conditions were found to have a significant effect on the pellet shape and hardness profile. Pellets with maximum sphericity and hardness exhibited no crystalline peak after extrusion. The rate of drug release was affected mainly by pellet size, where smaller pellets released the drug faster. All optimized formulations were found to be of superior hardness and not friable. The flow properties of optimized pellets were excellent with high bulk and tapped density.

A critical view of the 'social reinsertion' concept and its implications for the practice of psychologists in the area of mental health in the Brazilian Unified Health System (Sistema Único de Saúde).

Improving psychological practice in mental health services in the Brazilian Unified Health System (Sistema Único de Saúde) requires a critical analysis of core concepts of the psychiatric reform, such as 'social reinsertion'. This analysis, oriented by the dialectics of exclusion/inclusion, showed that this concept is impregnated with the adaptation paradigm and asylum view which prevents its effective implantation. The results suggest it is necessary to include social aspects in the discussion of mental health, articulating it with networks of social work and recuperating the revolutionary aspects of the psychiatric reform, thus demarcating the political nature of professional practices.