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1.
Mol Pharm ; 21(4): 1861-1871, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38416030

RESUMEN

This study aims to investigate key variables affecting the dissolution of amorphous pharmaceuticals. We examined sample treatment methods (centrifugation vs syringe filtration), time delays between sample collection and processing (immediate, 2, or 24 h), and different sample preparations (bare powder, capsules, or tablets). These factors were evaluated through both sink and nonsink dissolution experiments, using controlled supersaturation conditions (sink index ≈ 0.1) with amorphous solid dispersions (ASDs) containing low-substituted hydroxypropyl cellulose (L-HPC) and either indomethacin or posaconazole as model drugs. Our results highlighted the significant impact of syringe filtration on nonsink dissolutions, particularly the notable reduction in dissolved drug concentration, possibly due to filtration-induced precipitation. Moreover, introducing a delay of 2 or 24 h between sample collection and quantitation under nonsink conditions led to substantial concentration changes. This effect was not as pronounced when samples underwent centrifugation, and only the analysis was delayed for 2 h. The findings also emphasize the importance of accounting for delays introduced by pharmaceutical formulations, particularly in assessing the kinetic-solubility profiles of ASDs. This research offers valuable insights into the field of ASDs, enhancing our understanding of how these variables can influence dissolution results.


Asunto(s)
Cristalización , Solubilidad , Liberación de Fármacos
2.
Drug Dev Ind Pharm ; 47(5): 725-734, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34038291

RESUMEN

OBJECTIVE: To perform the solid-state characterization and the in vitro-in vivo correlation (IVIVC) of three batches of efavirenz (EFV) active pharmaceutical ingredients. SIGNIFICANCE: EFV is an effective anti-HIV drug. Due to the poor aqueous solubility, the rate and extent of EFV absorption deeply depend on its dissolution characteristics. METHODS: Thermal analyses, x-ray diffraction, and particle size distribution were performed. The saturation solubility and dissolution profiles were assessed in 0.5% (w/v) sodium lauryl sulfate (SLS), fasted-state simulated intestinal fluid (FaSSIF), and fed-state simulated intestinal fluid (FeSSIF) using a flow-through cell. Each batch was orally administered to Wistar rats and the pharmacokinetic parameters were correlated with those obtained from in vitro dissolution. RESULTS: All batches of EFV consisted polymorph I. EFV-A presented the lowest particle size distribution [d(v,0.5) = 197.8 µm; d(v,0.9) = 444.6 µm] followed by EFV-B [d(v,0.5) = 223.9 µm; d(v,0.9) = 481.1 µm], and EFV-C [d(v,0.5) = 240.8 µm; d(v,0.9) = 497.3 µm]. The saturated solubility in FaSSIF was 36% and 40% of that in FeSSIF and SLS, respectively. EFV-A presented the fastest rate and largest extension of dissolution than EFV-B and C (79.15%, 69.93% and 54.22%, respectively, as well as the highest maximum plasma concentration. Levels B, C, and multiple-C of IVIVC models were achieved. CONCLUSION: The FaSSIF medium discriminated the dissolution profiles of EFV APIs. Small differences in particle size distribution had a significant impact on the biopharmaceutical parameters of EFV, suggesting that strict control of such parameter is an important aspect during API development and drug formulation.


Asunto(s)
Benzoxazinas , Alquinos , Animales , Ciclopropanos , Composición de Medicamentos , Ratas , Ratas Wistar , Solubilidad
3.
Gen Dent ; 69(4): 19-26, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34185664

RESUMEN

The objectives of this study were to determine the effectiveness of a mucoadhesive tablet of pilocarpine, 5 mg, for the treatment of xerostomia and verify its pharmacokinetic profile. The randomized, double-blind, crossover clinical trial involved 25 older adults (60 to 80 years) with xerostomia and hyposalivation who were randomly divided into groups A and B. Once daily, for 7 days, group A used a mucoadhesive tablet containing pilocarpine, while group B used a mucoadhesive tablet without the active ingredient (first intervention). After 7 days of washout (no treatment), use of the medications resumed for 7 days, with a crossover between groups (second intervention). Xerostomia was evaluated through a shortened version of the Summated Xerostomia Inventory-Dutch Version, and the unstimulated salivary flow (USF) and stimulated salivary flow (SSF) of the patients were measured. The patients were evaluated at baseline and 7, 14, and 21 days. Then, the pharmacokinetic profiles of mucoadhesive and conventional oral pilocarpine tablets were compared using saliva obtained from 8 patients. Both of the interventions resulted in a significant reduction in Summated Xerostomia Inventory scores and a significant increase in the mean USF (P < 0.05). A statistically significant increase in the mean SSF only occurred when pilocarpine was administered (P < 0.05). No significant adverse effects were found. The mucoadhesive tablet resulted in much higher salivary concentrations of pilocarpine than did the conventional oral tablet. Both formulations of the mucoadhesive tablet, with or without pilocarpine, relieved patients' dry mouth symptoms. Trial registration: Registro Brasileiro de Ensaios Clinicos (ReBEC) No. RBR-9qdnws.


Asunto(s)
Pilocarpina , Xerostomía , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Humanos , Persona de Mediana Edad , Saliva , Comprimidos , Xerostomía/tratamiento farmacológico
4.
Curr Med Chem ; 2024 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-39129289

RESUMEN

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of the circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers. OBJECTIVE: This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented, along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed. CONCLUSION: This review examines innovative approaches for HIV treatment, where various drug delivery systems have shown significant advantages, such as high drug encapsulation, improved solubility, and enhanced bioavailability both in vitro and in vivo. Strategies like cyclodextrins, solid dispersions, microneedles, and nanoparticles are explored to address challenges in drug solubility, bioavailability, and administration routes. Despite progress, obstacles like limited clinical trials and industrial scalability hinder the widespread adoption of these formulations, emphasizing the need for further research and collaboration to optimize and ensure accessibility of innovative HIV therapies, mainly in regions where access to HIV treatment is scarce and remains a challenge.

5.
Neurochem Res ; 38(4): 726-31, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23334713

RESUMEN

2-[(2,6-dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile), 5TIO1, is a new 2-aminothiophene derivative with a promising pharmacological activity. The aim of this work was to evaluate the potential anxiolytic effect of 5TIO1 in animal models. In the elevated plus-maze test, 5TIO1 (0.1, 1.0 and 10.0 mg/kg, i.p) increased the time of permanence and the number of entries in the open arms. In the light/dark box test, 5TIO1 at dose of 0.1 mg/kg (i.p) also showed anxiolytic-like effect indicated by an increase in the time spent in the light box, similar to diazepam 2.0 mg/kg (i.p). 5TIO1 groups did not change locomotor and coordination activities in open field and rotarod tests, respectively, when compared to vehicle. Dose dependent process was not observed and the anxiolytic effects demonstrated were not completely reversed by flumazenil 25 mg/kg (i.p). Our results suggest that 5TIO1 can bind with other receptors, besides the benzodiazepine site of the GABA receptor in mouse brain.


Asunto(s)
Ansiolíticos/farmacología , Bases de Schiff/farmacología , Tiofenos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Receptores de GABA-A/efectos de los fármacos
6.
Expert Opin Ther Pat ; 33(1): 1-15, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36755421

RESUMEN

INTRODUCTION: Leprosy is a neglected, infectious, granulomatous and chronic disease caused by the pathological agent Mycobacterium leprae. The course of the disease is more aggressive in patients under 15 years of age, but the current treatment offered worldwide consists of solid forms, by the combination of antibiotics such as rifampicin, clofazimine and dapsone. This represents results in lack of adherence in pediatric patients and drug therapy failure, although numerous formulations and technologies have already been developed. AREA COVERED: This study aims to analyze the technological evolution of the pharmaceutical treatment of leprosy, aimed at children. A review of patents around the world was conducted to look for technical and clinical aspects of formulations and devices. EXPERT OPINION: Innovative formulations for pediatric patients were classified according to the routes of administration as oral, inhalable, injectable and transdermal. The formulations were organized as alternatives for pediatric therapy, taking into account the physicochemical aspects of drugs and the physiological aspects of pediatric patients. Among the difficulties for the patented formulations to reach the market, of special note is the low stability of the physicochemical characteristics of the drugs. Optimization of formulations would favor the pediatric treatment of leprosy, aiming at therapeutic success.


Asunto(s)
Leprostáticos , Lepra , Humanos , Niño , Leprostáticos/uso terapéutico , Preparaciones Farmacéuticas , Patentes como Asunto , Lepra/tratamiento farmacológico , Lepra/microbiología , Rifampin/uso terapéutico
7.
Int J Biol Macromol ; 242(Pt 1): 124737, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37148931

RESUMEN

Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.


Asunto(s)
Anacardium , Quitosano , Diabetes Mellitus , Nanopartículas , Humanos , Insulina , Quitosano/química , Anacardium/química , Diabetes Mellitus/tratamiento farmacológico , Nanopartículas/química , Portadores de Fármacos/química , Administración Oral , Tamaño de la Partícula
8.
Int J Biol Macromol ; 230: 123272, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36649864

RESUMEN

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.


Asunto(s)
Anacardium , Nanopartículas , Trypanosoma cruzi , Reproducibilidad de los Resultados , Nanopartículas/química , Liberación de Fármacos , Polímeros/farmacología , Concentración de Iones de Hidrógeno , Portadores de Fármacos/farmacología
9.
Curr Med Chem ; 29(11): 1936-1958, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34212827

RESUMEN

BACKGROUND: Tuberculosis is a chronic respiratory disease caused by Mycobacterium tuberculosis. The common treatment regimens of tuberculosis are lengthy with adverse side effects, low patient compliance, and antimicrobial resistance. Drug delivery systems (DDSs) can overcome these limitations. OBJECTIVE: This review aims to summarize the latest DDSs for the treatment of tuberculosis. In the first section, the main pharmacokinetic and pharmacodynamic challenges posed by the innate properties of the drugs are put forth. The second section elaborates on the use of DDS to overcome the disadvantages of the current treatment of tuberculosis. CONCLUSION: We reviewed research articles published in the last 10 years. DDSs can improve the physicochemical properties of anti-tuberculosis drugs, improving solubility, stability, and bioavailability, with better control of drug release and can target alveolar macrophages. However, more pre-clinical studies and robust bio-relevant analyses are needed for DDSs to become a feasible option to treat patients and attract investors.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Tuberculosis/tratamiento farmacológico
10.
Expert Opin Ther Pat ; 32(1): 89-114, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34424127

RESUMEN

INTRODUCTION: Many drugs used to combat schistosomiasis, Chagas disease, and leishmaniasis (SCL) have clinical limitations such as: high toxicity to the liver, kidneys and spleen; reproductive, gastrointestinal, and heart disorders; teratogenicity. In this sense, drug delivery systems (DDSs) have been described in the literature as a viable option for overcoming the limitations of these drugs. An analysis of the level of development (TRL) of patents can help in determine the steps that must be taken for promising technologies to reach the market. AREAS COVERED: This study aimed to analyze the stage of development of DDSs for the treatment of SCL described in patents. In addition, we try to understand the main reasons why many DDSs do not reach the market. In this study, we examined DDSs for drugs indicated by WHO and treatment of SCL, by performing a search for patents. EXPERT OPINION: In this present work we provide arguments that support the hypothesis that there is a lack of integration between academia and industry to finance and continue research, especially the development of clinical studies. We cite the translational research consortia as the potential alternative for developing DDSs to combat NTDs.


Asunto(s)
Patentes como Asunto , Esquistosomiasis , Sistemas de Liberación de Medicamentos , Humanos , Enfermedades Desatendidas/tratamiento farmacológico , Esquistosomiasis/tratamiento farmacológico , Tecnología
11.
Int J Biol Macromol ; 193(Pt A): 481-490, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34710475

RESUMEN

Trees of the genus Sterculia produce polysaccharide-rich exudates, such as karaya gum (Sterculia urens), chicha gum (Sterculia striata), and Sterculia foetida gum. These anionic biomaterials are biodegradable, with high viscosity, low toxicity, and gelling properties in aqueous media. According to these properties, they show promising applications as a polymer matrix for use in drug delivery systems. For this application, both the chemically modified and the unmodified polysaccharide are used. This review focuses on analyzing the state of the art of recent studies on the use of Sterculia gums in a variety of pharmaceutical forms, such as tablets, hydrogels, micro/nanoparticles, and mucoadhesive films. Sterculia gums-based delivery systems have potential to be explored for new drug delivery systems.


Asunto(s)
Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos , Gomas de Plantas/química , Sterculia/metabolismo , Liberación de Fármacos
12.
Int J Biol Macromol ; 193(Pt A): 450-456, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34688680

RESUMEN

Enoxaparin is an effective biological molecule for prevention and treatment of coagulation disorders. However, it is poorly absorbed in the gastrointestinal tract. In this study, we developed an Eudragit® L100 coated chitosan core shell nanoparticles for enoxaparin oral delivery (Eud/CS/Enox NPs) through a completely eco-friendly method without employing any high-energy homogenizer technique and any organic solvents. Spherical nanocarriers were successfully prepared with particle size lower than 300 nm, polydispersity index about 0.12 and zeta potential higher than +25 mV, entrapment efficiency greater than 95% and the in vitro release behavior confirms the good colloidal stability and the successful Eudragit® L100 coating process demonstrated by negligible cumulative enoxaparin release (<10%) when the particles are submitted to simulated gastric fluid conditions. Finally, we demonstrated that the core-shell structure of the particle influenced the drug release mechanism of the formulations, indicating the presence of the Eudragit® L100 on the surface of the particles. These results suggested that enteric-coating approach and drug delivery nanotechnology can be successfully explored as potential tools for oral delivery of enoxaparin.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Enoxaparina/química , Nanopartículas/química , Liberación de Fármacos , Tamaño de la Partícula
13.
Int J Biol Macromol ; 190: 801-809, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34508723

RESUMEN

We developed a new hydrophobic polymer based on angico gum (AG), and we produced new nanoparticles to expand the applications of natural polysaccharides in nanomedicine. Phthalate angico gum (PAG) was characterized by 1H NMR, FTIR, elementary analysis, solubility, XRD, and TG. PAG was a hydrophobic and semi-crystalline material, a relevant characteristic for drug delivery system applications. As a proof of concept, nevirapine (NVP) was selected for nanoparticles development. Plackett-Burman's experimental design was used to understand the influence of several factors in nanoparticles production. PAG proved to be a versatile material for producing nanoparticles with different characteristics. Optimized nanoparticles were produced using desirability parameters. NVP-loaded PAG nanoparticles formulation showed 202.1 nm of particle size, 0.23 of PDI, -17.1 of zeta potential, 69.8 of encapsulation efficiency, and promoted modified drug release for 8 h. Here we show that PAG presents as a promising biopolymer for drug delivery systems.


Asunto(s)
Tecnología Química Verde , Nanopartículas/química , Nanotecnología , Ácidos Ftálicos/química , Gomas de Plantas/química , Liberación de Fármacos , Humanos , Microscopía de Fuerza Atómica , Peso Molecular , Nevirapina/farmacología , Tamaño de la Partícula , Espectroscopía de Protones por Resonancia Magnética , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría , Difracción de Rayos X
14.
Carbohydr Polym ; 254: 117226, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33357841

RESUMEN

Chemical modification of polysaccharides is an important approach for their transformation into customized matrices that suit different applications. Microwave irradiation (MW) has been used to catalyze chemical reactions. This study developed a method of MW-initiated synthesis for the production of phthalated cashew gum (Phat-CG). The structural characteristics and physicochemical properties of the modified biopolymers were investigated by FTIR, GPC, 1H NMR, relaxometry, elemental analysis, thermal analysis, XRD, degree of substitution, and solubility. Phat-CG was used as a matrix for drug delivery systems using benznidazole (BNZ) as a model drug. BNZ is used in the pharmacotherapy of Chagas disease. The nanoparticles were characterized by size, PDI, zeta potential, AFM, and in vitro release. The nanoparticles had a size of 288.8 nm, PDI of 0.27, and zeta potential of -31.8 mV. The results showed that Phat-CG has interesting and promising properties as a new alternative for improving the treatment of Chagas disease.


Asunto(s)
Anacardium/química , Sistemas de Liberación de Medicamentos , Gomas de Plantas/química , Enfermedad de Chagas/tratamiento farmacológico , Simulación por Computador , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Microscopía de Fuerza Atómica , Microondas , Estructura Molecular , Nanopartículas/química , Nitroimidazoles/administración & dosificación , Tamaño de la Partícula , Ácidos Ftálicos/química , Espectroscopía Infrarroja por Transformada de Fourier , Tripanocidas/administración & dosificación
15.
AAPS PharmSciTech ; 11(3): 1391-6, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20824514

RESUMEN

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van't Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68°C (∆H, 119.71 J g(-1)), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76-319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.


Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Excipientes/química , Nitroimidazoles/química , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos , Estabilidad de Medicamentos , Calor , Humanos , Temperatura de Transición
16.
Colloids Surf B Biointerfaces ; 193: 111055, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32403034

RESUMEN

In this work, synthesis of sodium dodecyl sulfate (SDS) organomodified LDH Zn2Al carrying glibenclamide (GLIB) was performed in one step and in one-pot to obtain nanoparticles (NP). XRD data showed GLIB adsolubilization (d = 14.03 Å) and NP coating with Eudragit L100®. In addition, thermal and XRD data showed exfoliated/intercalated nanocomposite for NP S5 (LDH associated with SDS and Eudragit L100®). LDH organophilization and GLIB intercalation reduced surface area (SBET 23.58 m2/g) and NP size (469 nm). In addition, the change in zeta potential (-35.5 ζ) relative to pristine LDH (SBET 41.34 m2/g, 688.8 nm and +14 ζ) indicated that LDH functionalization seems an appropriate approach to produce NP with greater colloidal stability and enhanced functionality. The zinc release data from the LDH matrix (2.96 % ±0.002 ppm) showed the effectiveness of the coating in acid medium (pH 1.2) and the release data from GLIB showed the kinetics of release of zero order with release in simulated intestinal medium (pH 7.4) of 88 % and 73 % (24 h) for uncoated and coated NP, respectively. All NP were considered biocompatible in the WST-1 assay on BALB 3T3 fibroblast strains making these NP promising therapeutically.


Asunto(s)
Materiales Biocompatibles/síntesis química , Gliburida/química , Hidróxidos/química , Nanopartículas/química , Materiales Biocompatibles/química , Ensayo de Materiales
17.
J Chromatogr Sci ; 57(2): 156-162, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30496348

RESUMEN

OBJECTIVE: To develop an analytical method to simultaneous quantification of benznidazole (BNZ) and posaconazole (POS) by high-performance liquid chromatography with diode-array detection (HPLC-DAD) using design of experiments. METHODS: Percentages of organic phase, buffer pH and flow rates of mobile phase were selected as independent variables by full factorial design (33), totaling 27 experiments. Significant factors were evaluated using factorial analysis of variance with 95% confidence level. Method optimization was performed using desirability profiles, considering BNZ/POS chromatographic resolution and peak areas. Further, the method was evaluated regarding its suitability and properly validated according to the international compendiums using the parameters: specificity, linearity, accuracy, precision, limit of detection and limit of quantification. RESULTS: The optimized method was achieved using Discovery® C8 column (250 mm × 4.6 mm; 5 µm particle size), methanol/acetate buffer (pH 3.5)(71:29) and detection at 260 nm. Retention times were 3.6 and 7.6 min for BNZ and POS, respectively, with good suitability of system and it was specific and linear (r2 >0.99) for both drugs, proving the efficiency of the method even in the presence of degradation products of POS. CONCLUSION: This new method is a great alternative to perform reliable, faster and cheaper analysis since the simultaneous quantification of the association BZN/POS is not reported yet in the literature.

18.
Eur J Pharm Sci ; 133: 79-85, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-30890364

RESUMEN

The aim of this study was to evaluate the potential of combining multiple ASDs based on water soluble and insoluble polymers to reach and maintain poorly soluble posaconazole (PCZ) supersaturation over time. ASDs of PCZ were obtained with PVP/VA64 or an ammonio methacrylate copolymer by solvent evaporation method with a fixed 20% (wt/wt%) drug loading ratio and physical mixtures of these ASDs were prepared at various proportions. ASDs were characterized by Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) and compared to their respective physical mixture with crystalline PCZ. Crystalline PCZ equilibrium solubility was determined at pH 1.2-2 range. Dissolution profiles were constructed under non-sink condition with an adapted dissolution system. PXRD analysis demonstrated that both ASDs were at the amorphous state and FT-IR spectroscopy revealed that the analytical signal of PCZ was also absent in both ASDs. Equilibrium solubility of crystalline PCZ varied between 26.36 ±â€¯0.32 (pH 2) to 609.33 ±â€¯3.68 (pH 1.2) µg/mL. All ASDs reached higher concentrations than the equilibrium solubility of crystalline PCZ during dissolution. PVP/VA64 ASDs showed dominance over PCZ dissolution and recrystallization rates whereas Eudragit RS PO ASD alone did not cause PCZ recrystallization whatsoever. The combination containing 20 mg PVP/VA64 + 80 mg Eudragit RS PO as PCZ carriers obtained the highest AUC, suggesting that even after the PVP/VA64 part was completely dissolved, reaching a concentration above crystalline PC Cs, the insoluble polymer could still release PCZ slowly and maintain supersaturation over time. The research demonstrated a potential of combining multiple ASDs to achieve distinct dissolution profiles while increasing the kinetic solubility of poorly soluble drugs.


Asunto(s)
Antifúngicos/química , Excipientes/química , Ácidos Polimetacrílicos/química , Pirrolidinas/química , Triazoles/química , Compuestos de Vinilo/química , Cristalización , Formas de Dosificación , Liberación de Fármacos , Cinética , Solubilidad
19.
Pharmacy (Basel) ; 7(2)2019 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-31248173

RESUMEN

The study objective is to describe patients and professionals' perspectives on the Tuberculosis Control Program (PCT) in Recife, Brazil, contributing to the program evaluation. A cross-sectional study was conducted in three purposively selected sites, representing the three levels of care in the public health system. All eligible PCT patients in sites A, B and C were invited to participate (n = 123). Physicians, nurses, pharmacists and community health agents providing care to PCT patients in these sites, plus their managers, were purposively selected. Data were collected by means of interviews with 44 patients and a questionnaire to 24 professionals. Instruments encompassed previously published items to capture stakeholders' perspectives (16 and 12 closed-questions, respectively), grouped into categories. The overall evaluation by patients was unsatisfactory (median score 35%; third quartile below 50%; interquartile range 21.9%). Analysis of scores by categories showed that opinions about organizational accessibility were significantly worse than about economic and geographical accessibility, taken together. Overall the median score attributed by professionals was 52% (third quartile below 65%). Professionals had significantly worse opinions about diagnosis, clinical and laboratory assistance. Patients and professionals' perspectives highlight potential opportunities for improvement. Our findings can be used by managers as a starting point for shared decision-making, potentially contributing to a better performance of the PCT in Recife and, consequently, reducing the risk posed by tuberculosis.

20.
Carbohydr Polym ; 213: 176-183, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30879658

RESUMEN

This work describes a solvent-free method for the chemical modification of cashew gum (Anacardium occidentale L.) using phthalic anhydride in different proportions with different reaction times. Four biopolymers were synthesized and characterized by FTIR, NMR, and elemental analysis. A computational chemistry study was conducted to understand better the reaction. Phthalated cashew gum was used in preparation of silver nanoparticles (AgNPs) by a conventional route, using sodium borohydride (NaBH4) as reducing agent, and for green route. AgNPs were evaluated for antimicrobial activity and characterized by UV-Vis spectroscopy, FTIR, nanoparticle tracking analysis, Zeta Potential analysis, and atomic force microscopy. AgNPs produced by the green route had an average size of 51.9 nm and Zeta Potential of -55.8 mV, and AgNPs produced by the conventional method had an average size of 47.7 nm and Zeta Potential of -39.3 mV. AgNPs synthesized using phthalated cashew gum showed antimicrobial activity against Staphylococcus aureus and Escherichia coli.


Asunto(s)
Anacardium/química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanopartículas del Metal/química , Plata/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Ácidos Ftálicos/química , Plata/química , Relación Estructura-Actividad
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