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1.
Rev Esp Enferm Dig ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648343

RESUMO

We report the available evidence demonstrating the biosimilarity of ABP 501 (AMGEVITA®, adalimumab-atto) to its reference product (RP) (Humira®, adalimumab), and the rationale for the extrapolation of the results obtained with the RP in inflammatory bowel disease (IBD) to ABP 501.

2.
J Clin Invest ; 131(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33332283

RESUMO

Mutant isocitrate dehydrogenase 1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into 2 molecular subgroups: 1p/19q codeletion/TERT-promoter mutations or inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) and TP53. This work focuses on glioma subtypes harboring mIDH1, TP53, and ATRX inactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of D-2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma-bearing mice. Also, D-2HG inhibition elicited anti-mIDH1 glioma immunological memory. In response to D-2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in WT-IDH gliomas. Thus, we combined D-2HG inhibition/IR/TMZ with anti-PDL1 immune checkpoint blockade and observed complete tumor regression in 60% of mIDH1 glioma-bearing mice. This combination strategy reduced T cell exhaustion and favored the generation of memory CD8+ T cells. Our findings demonstrate that metabolic reprogramming elicits anti-mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data support the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients.

3.
Int J Mol Sci ; 21(24)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33348922

RESUMO

In this review, we discuss the molecular characteristics, development, evolution, and therapeutic perspectives for pediatric high-grade glioma (pHGG) arising in cerebral hemispheres. Recently, the understanding of biology of pHGG experienced a revolution with discoveries arising from genomic and epigenomic high-throughput profiling techniques. These findings led to identification of prevalent molecular alterations in pHGG and revealed a strong connection between epigenetic dysregulation and pHGG development. Although we are only beginning to unravel the molecular biology underlying pHGG, there is a desperate need to develop therapies that would improve the outcome of pHGG patients, as current therapies do not elicit significant improvement in median survival for this patient population. We explore the molecular and cell biology and clinical state-of-the-art of pediatric high-grade gliomas (pHGGs) arising in cerebral hemispheres. We discuss the role of driving mutations, with a special consideration of the role of epigenetic-disrupting mutations. We will also discuss the possibilities of targeting unique molecular vulnerabilities of hemispherical pHGG to design innovative tailored therapies.


Assuntos
Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Terapia de Alvo Molecular , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Glioma/genética , Glioma/patologia , Humanos , Gradação de Tumores
4.
Rev Esp Enferm Dig ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33371701

RESUMO

Introduction We find a rising number of patients receiving antiplatelet and anticoagulation therapy who require endoscopic retrograde cholangiopancreatography (ERCP), probably due to a higher incidence of the increased morbidity of older patients. Considering the increasingly spreading use of direct oral anticoagulants (DOACs), we want to study about the influence of these factors on the possibility of hemorrhage after ERCP in our center. MATERIAL AND METHODS: We collected data from all the examinations carried out in the years 2017 and 2018, which included 797 examinations on 588 patients. Collected data included: personal history of the patients, results of the test and follow-up. RESULTS: In our study, the percentage of post-ERCP bleeding was 4.6% (n=37). With regard to the severity, in 21.6% (n=8) of the cases the bleeding was mild, it was moderate in 59.5% (n=22), and severe in 18.9% (n=7). Previous cardiopathy, antiplatelet therapy, anticoagulation therapy, treatment with DOACs, having a pancreatic stent, and lithiasis removal double the risk of bleeding after ERCP. Having a sphincterotomy represents an over five-fold increase of the risk. CONCLUSION: In the multivariate analysis, we observed a statistically significant increase of bleeding among patients treated with DOACs, compared to patients who receive anticoagulation with acenocoumarol or low-molecular-weight heparins (LMWH).

6.
Clin Cancer Res ; 26(15): 4080-4092, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32332014

RESUMO

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, Activin A receptor type I (ACVR1)-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy. EXPERIMENTAL DESIGN: We utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNA-sequencing analysis on neurospheres harboring mACVR1. mACVR1 neurospheres were implanted into the pons of immune-competent mice to test the therapeutic efficacy and toxicity of immune-stimulatory gene therapy using adenoviruses expressing thymidine kinase (TK) and fms-like tyrosine kinase 3 ligand (Flt3L). mACVR1 neurospheres expressing the surrogate tumor antigen ovalbumin were generated to investigate whether TK/Flt3L treatment induces the recruitment of tumor antigen-specific T cells. RESULTS: Histologic analysis of mACVR1 tumors indicates that they are localized in the brainstem and have increased downstream signaling of bone morphogenetic pathway as demonstrated by increased phospho-smad1/5 and Id1 levels. Transcriptome analysis of mACVR1 neurosphere identified an increase in the TGFß signaling pathway and the regulation of cell differentiation. Adenoviral delivery of TK/Flt3L in mice bearing brainstem gliomas resulted in antitumor immunity, recruitment of antitumor-specific T cells, and increased median survival (MS). CONCLUSIONS: This study provides insights into the phenotype and function of the tumor immune microenvironment in a mouse model of brainstem glioma harboring mACVR1. Immune-stimulatory gene therapy targeting the hosts' antitumor immune response inhibits tumor progression and increases MS of mice bearing mACVR1 tumors.

7.
Expert Opin Biol Ther ; 20(3): 305-317, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31959027

RESUMO

Introduction: The field of neuro-oncology has experienced significant advances in recent years. More is known now about the molecular and genetic characteristics of glioma than ever before. This knowledge leads to the understanding of glioma biology and pathogenesis, guiding the development of targeted therapeutics and clinical trials. The goal of this review is to describe the state of basic, translational, and clinical research as it pertains to biological and synthetic pharmacotherapy for gliomas.Areas covered: Challenges remain in designing accurate preclinical models and identifying patients that are likely to respond to a particular targeted therapy. Preclinical models for therapeutic assessment are critical to identify the most promising treatment approaches.Expert opinion: Despite promising new therapeutics, there have been no significant breakthroughs in glioma treatment and patient outcomes. Thus, there is an urgent need to better understand the mechanisms of treatment resistance and to design effective clinical trials.

9.
Nutrients ; 11(11)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703400

RESUMO

This study aimed to complete the scientific basis for the validation of a coffee silverskin extract (CSE) as a novel food ingredient according to European legislation. Nutritional value, safety, effects on biochemical biomarkers and excretion of short chain fatty acids (SCFAs) in vivo of CSE were assessed. Proteins, amino acids, fat, fatty acids, fiber, simple sugars and micronutrients were analyzed. For the first time, toxicological and physiological effects were evaluated in vivo by a repeated-dose study in healthy Wistar rats. Hormone secretion, antioxidant (enzymatic and no-enzymatic) and anti-inflammatory biomarkers, and dietary fiber fermentability of CSE (analysis of SCFAs in feces) were studied in biological samples. This unique research confirms the feasibility of CSE as a human dietary supplement with several nutrition claims: "source of proteins (16%), potassium, magnesium, calcium and vitamin C, low in fat (0.44%) and high in fiber (22%)". This is the first report demonstrating that its oral administration (1 g/kg) for 28 days is innocuous. Hormone secretion, antioxidant or anti-inflammatory biomarkers were not affected in heathy animals. Total SCFAs derived from CSE fiber fermentation were significantly higher (p < 0.05) in male treated rats compared to male control rats. All the new information pinpoints CSE as a natural, sustainable and safe food ingredient containing fermentable fiber able to produce SCFAs with beneficial effects on gut microbiota.


Assuntos
Café , Extratos Vegetais , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Fibras na Dieta/análise , Ácidos Graxos Voláteis/análise , Feminino , Masculino , Valor Nutritivo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar
10.
Heliyon ; 5(7): e02071, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31360787

RESUMO

In this work, waste expanded polystyrene (WEPS) was irradiated with gamma rays, ranging doses from 100 kGy to 1,000 kGy. After irradiation, the WEPS had decrease on its glass transition temperature (Tg), as consequence of the scissions of its polymer chains. Then, the irradiated WEPS was sulfonated, and its degree of sulfonation (DS) was measured. The highest DS value, 46.6%, was obtained for an irradiation dose of 200 kGy. The sulfonated and irradiated polystyrene (denominated as iS-WEPS), was used as a support of iron oxide nanoparticles. Such composite system was denominated (FeO-NPs + iS-WEPS). The results show nanoparticle sizes of 31.5 nm containing 21.97% iron oxide. The composites followed a pseudo-second order model, with a maximum adsorption capacity of 20 mg/g, and an equilibrium time of 30 min, according to the Langmuir model. Moreover, the optimal conditions followed by the Fenton process were: pH = 3.2, H2O2 concentration = 0.32 mM/L, composite concentration (FeO-NPs + iS-WEPS) = 2 g/L, and a reaction time 20 min. Finally, 99% removal of indigo carmine dye was achieved, and a reduction of 83% of COD in textile wastewater.

11.
Semin Thorac Cardiovasc Surg ; 31(4): 828-834, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31005576

RESUMO

Deleterious long-term effects of chronic pulmonary regurgitation after repair of tetralogy of Fallot have become evident during the last decades. Subsequently, some groups have developed strategies to spare the pulmonary valve function at the time of repair with good early results. However, mid-term outcomes are scarce in the literature and in some cases controversial. The aim of our study is to report our results mid-term with valve-sparing repair of tetralogy of Fallot. We retrospectively reviewed patients undergoing tetralogy of Fallot repair and having preservation of the pulmonary valve with intraoperative dilation at our institution. From June 2009 through June 2017, 42 patients underwent valve-sparing tetralogy of Fallot repair. Median age and weight at surgery were 5.2 months and 7.2 kg. Median preoperative pulmonary valve diameters and Z scores by echocardiography were 6.4 mm (range 4.5-11 mm) and -2.3 (range -1.3 to -4.5). No patient died in our series. For a median follow-up of 45 months, the pulmonary valve has grown by Z score (P < 0.0001) as well as the pulmonary trunk (P= 0.00216). Significant pulmonary regurgitation has developed in 9 patients (21.4%). No patient has required reintervention/reoperation for recurrent right ventricular outflow tract obstruction. Patients with tetralogy of Fallot who had valve-sparing repair with intraoperative dilation of the pulmonary valve show good early and mid-term results with respect to right ventricular outflow tract obstruction. The pulmonary valve annulus and the pulmonary trunk grow through follow-up. Progressive development of significant pulmonary regurgitation is seen in more than 20% of patients. Long-term data with this approach and comparison with a population of patients undergoing a transannular patch repair are required to establish the real utility of this approach.


Assuntos
Valvuloplastia com Balão , Procedimentos Cirúrgicos Cardíacos , Valva Pulmonar/fisiopatologia , Tetralogia de Fallot/cirurgia , Valvuloplastia com Balão/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia , Feminino , Humanos , Lactente , Masculino , Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
12.
An. pediatr. (2003. Ed. impr.) ; 90(4): 219-223, abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-186612

RESUMO

Introducción: El objetivo de este estudio fue recopilar datos retrospectivos sobre la prescripción de clopidogrel y describir las condiciones de uso en la población pediátrica de un hospital de referencia de nivel terciario y evaluarlas con base en la evidencia disponible. Pacientes y métodos: Estudio observacional, descriptivo y retrospectivo realizado entre marzo de 2010 y marzo de 2017. Los criterios de inclusión fueron: 100% de los pacientes menores de 18 años que fueron dados de alta de nuestro hospital con clopidogrel como tratamiento domiciliario en el período de estudio. Se recogieron los siguientes datos: datos demográficos, diagnóstico, indicación de clopidogrel, fecha de inicio y de finalización del tratamiento, presencia o ausencia de tratamiento concomitante con ácido acetilsalicílico u otros antiagregantes plaquetarios o anticoagulantes, tratamiento concomitante con inhibidores de la bomba de protones, efectividad y efectos adversos. Resultados: Un total de 11 pacientes se incluyeron en el estudio (45% hombres). La edad promedio fue de 3,1 años (rango: 1 mes-8 años). La dosis recomendada de clopidogrel fue de 0,2 mg/kg/día en todos los individuos, recibiendo tratamiento concomitante con ácido acetilsalicílico 10/11 pacientes para optimizar la terapia antiplaquetaria. Ningún niño recibió tratamiento concomitante con anticoagulantes y solo uno de ellos recibió tratamiento con inhibidores de la bomba de protones. No se observaron trastornos hemorrágicos u otros efectos adversos asociados con clopidogrel. Conclusión: Según nuestra experiencia, la dosis de clopidogrel de 0,2 mg/kg/día demostró ser una estrategia segura y efectiva, independientemente de la edad del paciente. La buena tolerancia observada podría estar asociada con el ajuste de la dosis óptima para lograr la agregación plaquetaria sin aumentar el riesgo de efectos adversos


Introduction: The aim of this study was to collect retrospective data on the prescription of clopidogrel, describe the conditions of its use in the paediatric population of a tertiary referral hospital, and evaluate its use based on the current scientific evidence. Patients and methods: We conducted a retrospective, observational and descriptive study between March 2010 and March 2017. We included all patients under the age of 18 who were discharged from our hospital for home treatment with clopidogrel within the study period. We collected data on the following: demographic data, diagnosis, indication for clopidogrel, start and end date of treatment, presence or absence of concomitant treatment with acetylsalicylic acid or other antiplatelet or anticoagulant drugs, concomitant treatment with proton pump inhibitors, effectiveness, and adverse effects. Results: The study included a total of 11 patients (45% male). The mean age was 3.1 years (range, 1 month-8 years). The prescribed dose of clopidogrel was 0.2 mg/kg/day in all patients, and 10/11 patients received concomitant treatment with acetylsalicylic acid with the purpose of optimising antiplatelet therapy. None of the children received concomitant treatment with anticoagulants, and only one of them received treatment with a proton pump inhibitor. We did not find evidence of haemorrhagic complications or other adverse effects associated with clopidogrel. Conclusion: Based on our experience, a clopidogrel dose of 0.2 mg/kg/day is a safe and effective treatment, regardless of the patient's age. The good tolerance observed in our study could be related to the adjustment of the optimal dose with the aim of achieving platelet aggregation without increasing the risk of adverse effects


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos , Clopidogrel/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Inibidores da Agregação de Plaquetas/efeitos adversos , Centros de Atenção Terciária
13.
ACS Nano ; 13(2): 1365-1384, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30721028

RESUMO

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor, for which there is no cure. Treatment effectiveness for GBM has been limited due to tumor heterogeneity, an immunosuppressive tumor microenvironment (TME), and the presence of the blood-brain barrier, which hampers the transport of chemotherapeutic compounds to the central nervous system (CNS). High-density lipoprotein (HDL)-mimicking nanodiscs hold considerable promise to achieve delivery of bioactive compounds into tumors. Herein, we tested the ability of synthetic HDL nanodiscs to deliver chemotherapeutic agents to the GBM microenvironment and elicit tumor regression. To this end, we developed chemo-immunotherapy delivery vehicles based on sHDL nanodiscs loaded with CpG, a Toll-like receptor 9 (TLR9) agonist, together with docetaxel (DTX), a chemotherapeutic agent, for targeting GBM. Our data show that delivery of DTX-sHDL-CpG nanodiscs into the tumor mass elicited tumor regression and antitumor CD8+ T cell responses in the brain TME. We did not observe any overt off-target side effects. Furthermore, the combination of DTX-sHDL-CpG treatment with radiation (IR), which is the standard of care for GBM, resulted in tumor regression and long-term survival in 80% of GBM-bearing animals. Mice remained tumor-free upon tumor cell rechallenge in the contralateral hemisphere, indicating the development of anti-GBM immunological memory. Collectively, these data indicate that sHDL nanodiscs constitute an effective drug delivery platform for the treatment of GBM, resulting in tumor regression, long-term survival, and immunological memory when used in combination with IR. The proposed delivery platform has significant potential for clinical translation.


Assuntos
Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Imunoterapia/métodos , Lipoproteínas HDL/química , Lipoproteínas HDL/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel/química , Docetaxel/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Lomustina/química , Lomustina/uso terapêutico , Camundongos , Modelos Biológicos , Paclitaxel/química , Paclitaxel/uso terapêutico , Ratos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
14.
An Pediatr (Barc) ; 90(4): 219-223, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-30054222

RESUMO

INTRODUCTION: The aim of this study was to collect retrospective data on the prescription of clopidogrel, describe the conditions of its use in the paediatric population of a tertiary referral hospital, and evaluate its use based on the current scientific evidence. PATIENTS AND METHODS: We conducted a retrospective, observational and descriptive study between March 2010 and March 2017. We included all patients under the age of 18 who were discharged from our hospital for home treatment with clopidogrel within the study period. We collected data on the following: demographic data, diagnosis, indication for clopidogrel, start and end date of treatment, presence or absence of concomitant treatment with acetylsalicylic acid or other antiplatelet or anticoagulant drugs, concomitant treatment with proton pump inhibitors, effectiveness, and adverse effects. RESULTS: The study included a total of 11 patients (45% male). The mean age was 3.1 years (range, 1 month-8 years). The prescribed dose of clopidogrel was 0.2mg/kg/day in all patients, and 10/11 patients received concomitant treatment with acetylsalicylic acid with the purpose of optimising antiplatelet therapy. None of the children received concomitant treatment with anticoagulants, and only one of them received treatment with a proton pump inhibitor. We did not find evidence of haemorrhagic complications or other adverse effects associated with clopidogrel. CONCLUSION: Based on our experience, a clopidogrel dose of 0.2mg/kg/day is a safe and effective treatment, regardless of the patient's age. The good tolerance observed in our study could be related to the adjustment of the optimal dose with the aim of achieving platelet aggregation without increasing the risk of adverse effects.


Assuntos
Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Criança , Pré-Escolar , Clopidogrel/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Lactente , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Retrospectivos , Centros de Atenção Terciária
17.
Expert Opin Ther Targets ; 22(7): 599-613, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29889582

RESUMO

INTRODUCTION: ATRX is a chromatin remodeling protein whose main function is the deposition of the histone variant H3.3. ATRX mutations are widely distributed in glioma, and correlate with alternative lengthening of telomeres (ALT) development, but they also affect other cellular functions related to epigenetic regulation. Areas covered: We discuss the main molecular characteristics of ATRX, from its various functions in normal development to the effects of its loss in ATRX syndrome patients and animal models. We focus on the salient consequences of ATRX mutations in cancer, from a clinical to a molecular point of view, focusing on both adult and pediatric glioma. Finally, we will discuss the therapeutic opportunities future research perspectives. Expert opinion: ATRX is a major component of various essential cellular pathways, exceeding its functions as a histone chaperone (e.g. DNA replication and repair, chromatin higher-order structure regulation, gene transcriptional regulation, etc.). However, it is unclear how the loss of these functions in ATRX-null cancer cells affects cancer development and progression. We anticipate new treatments and clinical approaches will emerge for glioma and other cancer types as mechanistic and molecular studies on ATRX are only just beginning to reveal the many critical functions of this protein in cancer.


Assuntos
Glioma/genética , Retardo Mental Ligado ao Cromossomo X/genética , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética , Adulto , Animais , Criança , Montagem e Desmontagem da Cromatina/genética , Epigênese Genética , Glioma/patologia , Glioma/terapia , Humanos , Retardo Mental Ligado ao Cromossomo X/fisiopatologia , Mutação , Homeostase do Telômero , Talassemia alfa/fisiopatologia
20.
J Pharm Sci ; 106(12): 3604-3612, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28919383

RESUMO

An approximate solution is presented for the prediction of air entrapment during tableting. Assuming weak coupling of the deformation of the solid phase, the flow of interstitial air and a set of reasonable additional geometric assumptions, the general problem is reduced to 1 dimension. Experimental values of air permeability through tablet specimens of commonly used pharmaceutical excipients were obtained using a 3D printed test cell outfitted to a powder rheometer. Using these values, combined with a numerical solution of the governing partial differential equation, parametric studies are presented that demonstrate the importance of permeability, compaction speed, tablet size, and punch-die tolerance on air entrapment. In addition, a first-order approximation of the role of entrapped air on the measured radial tensile strength of formed tablets is presented.


Assuntos
Soluções/química , Comprimidos/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Excipientes/química , Tamanho da Partícula , Pós/química , Pressão , Resistência à Tração
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