Removal of azo dye using Fenton and Fenton-like processes: Evaluation of process factors by Box-Behnken design and ecotoxicity tests.

The conventional treatment of textile effluents is usually inefficient in removing azo dyes and can even generate more toxic products than the original dyes. The aim of the present study was to optimize the process factors in the degradation of Disperse Red 343 by Fenton and Fenton-like processes, as well as to investigate the ecotoxicity of the samples treated under optimized conditions. A Box-Behnken design integrated with the desirability function was used to optimize dye degradation, the amount of residual HO [HO], and the ecotoxicity of the treated samples (lettuce seed, Artemia salina, and zebrafish in their early-life stages).

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion.

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug.

Comparison of Clobetasol Propionate Generics Using Simplified In vitro Bioequivalence Method for Topical Drug Products.

Background: The aim of this paper is to evaluate a simple in vitro skin penetration experiment in which the drug is extracted from the whole skin piece as a test valid for formulation screening and optimization during development process, equivalence assessment during quality control or postapproval after changes to the product.

Methods: Twelve clobetasol propionate (CP) formulations (six creams and six ointments, being five generics and one reference from each formulation type) from the local market were used as a model to challenge the evaluated methodology in comparison to in vitro skin penetration following tape-stripping for drug extraction. To support the results, physicochemical tests for pH, viscosity, density and assay, as well as in vitro release were performed.

Microparticles prepared with 50-190kDa chitosan as promising non-toxic carriers for pulmonary delivery of isoniazid.

Chitosan biocompatibility and mucoadhesiveness make it an ideal polymer for antituberculotic drugs microcapsulation for pulmonary delivery. Yet, previous study indicated toxicity problems to J-774.1-cells treated with some medium molecular weight (190-310kDa) chitosan microparticles.

Versatile chromatographic method for catechin determination in development of topical formulations containing natural extracts.

Catechin is found in several natural sources, as Eugenia dysenterica and Syzygium cumini extracts. Its antioxidant and UV-protective properties suggest a potential use in cosmetic and dermatological formulations. A simple analytical method capable of giving support to experiments performed along the development of topical formulations containing this natural substance (i.

Use of mixture design in drug-excipient compatibility determinations: Thymol nanoparticles case study.

The objective of this work was to access thymol-excipient compatibility using an alternative protocol of mixture design subsidizing the development of nanostructures lipid carriers containing this drug. Simultaneous DTA-TG analyses associated with infrared spectroscopy were performed according to simplex centroid mixture designs with three components. Two designs were used: the design A containing stearic acid (SA), soybean lecithin (LC), and sodium taurodeoxycholate (TAU) and the design B, where TAU was replaced by polysorbate 80 (P80).

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated.

Solid effervescent formulations as new approach for topical minoxidil delivery.

Currently marketed minoxidil formulations present inconveniences that range from a grease hard aspect they leave on the hair to more serious adverse reactions as scalp dryness and irritation. In this paper we propose a novel approach for minoxidil sulphate (MXS) delivery based on a solid effervescent formulation. The aim was to investigate whether the particle mechanical movement triggered by effervescence would lead to higher follicle accumulation.

[Overview of regulatory aspects guiding tablet scoring].

Tablet scoring is a controversial but common practice used to adjust doses, facilitate drug intake, or lower the cost of drug treatment, especially in children and the elderly. The risks of tablet scoring are mainly related to inaccuracies in the resulting dose and stability problems. The aim of this article is to provide an overview of worldwide guidelines regarding tablet scoring.

Key Technical Aspects Influencing the Accuracy of Tablet Subdivision.

Tablet subdivision is a common practice used mainly for dose adjustment. The aim of this study was to investigate how the technical aspects of production as well as the method of tablets subdivision (employing a tablet splitter or a kitchen knife) influence the accuracy of this practice. Five drugs commonly used as subdivided tablets were selected.

Chromatographic method for clobetasol propionate determination in hair follicles and in different skin layers.

Clobetasol propionate (CLO) is a potent steroid used for the treatment of several dermatological diseases. Recent studies suggest its additional use in alopecia topical treatment, generating a demand for novel formulations with specific delivery into hair follicles. Hence, a selective analytical method for drug quantification in follicular structures and skin layers is required.

Preparation of benznidazole pellets for immediate drug delivery using the extrusion spheronization technique.

Recent advances in the treatment of Chagas disease have followed combinations of drugs that act synergistically against infection, predominantly including benznidazole (BNZ) and azoles derivatives. Possible incompatibilities between these drugs, slow dissolution of BNZ and dose adjustment difficulties are technological obstacles to the development of multidrug formulations. Thus, in the present study, BNZ pellets were developed using extrusion spheronization for immediate drug delivery.

Development of carvedilol-cyclodextrin inclusion complexes using fluid-bed granulation: a novel solid-state complexation alternative with technological advantages.

Objectives: This study sought to evaluate the achievement of carvedilol (CARV) inclusion complexes with modified cyclodextrins (HPβCD and HPγCD) using fluid-bed granulation (FB).

Methods: The solid complexes were produced using FB and spray drying (SD) and were characterised by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction, SEM, flowability and particle size analyses and in vitro dissolution.

Key Findings: The DSC, FTIR and powder X-ray diffraction findings suggested successful CARV inclusion in the modified β- and γ-cyclodextrins, which was more evident in acidic media.

Development and validation of a selective HPLC-UV method for thymol determination in skin permeation experiments.

Thymol is a natural monoterpene, whose antioxidant and antimicrobial properties suggest a potential use in topical formulations. A simple, precise and selective HPLC method for thymol determination in skin penetration studies was developed and validated in this paper. Separation was achieved with a RP-C18 column, mobile phase comprised of acetonitrile:water (35:65v/v), flow rate of 1.

Simultaneous determination of benznidazole and itraconazole using spectrophotometry applied to the analysis of mixture: A tool for quality control in the development of formulations.

The aim of this work was the development of an analytical procedure using spectrophotometry for simultaneous determination of benznidazole (BNZ) and itraconazole (ITZ) in a medicine used for the treatment of Chagas disease. In order to achieve this goal, the analysis of mixtures was performed applying the Lambert-Beer law through the absorbances of BNZ and ITZ in the wavelengths 259 and 321 nm, respectively. Diverse tests were carried out for development and validation of the method, which proved to be selective, robust, linear, and precise.

Effect of storage conditions on the stability of β-lapachone in solid state and in solution.

Objectives: In this work, the effects of several technological factors on the stability of β-lapachone (βLAP) in solution and in the solid state were investigated.

Methods: The effects of relative humidity and light on the stability of βLAP in the solid state were studied. Samples were characterized by liquid chromatography, thermal analysis, X-ray powder diffraction and optical microscopy.

Temperature-sensitive gels for intratumoral delivery of β-lapachone: effect of cyclodextrins and ethanol.

This work evaluated the potential of Pluronics (varieties F127 and P123) in combination with solubilizing agents to be used as syringeable in situ gelling depots of intratumoral β-lapachone (βLAP). Pluronic dispersions prepared at various concentrations in the absence and the presence of ethanol and randomly methylated β-cyclodextrin (RMβCD) were characterized regarding their rheological properties, drug solubilization capacity, and in vitro release. Pluronic F127 (18-23%) formulations combined high ability to solubilize βLAP (enhancement solubility factor up to 50), adequate gel temperature range (over 25 °C), and gel strength at 37 °C enough to guarantee the permanence of the formulation in the administration site for a period of time.

Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer.

Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas' disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design.

Fast dissolving β-lapachone particles and tablets: an approach using surface adsorption technique.

Background: β-lapachone (βLAP) is obtained from natural resources with promising preliminary results against the etiologic agent of Chagas disease. βLAP activity is associated with generation of free radical and inhibition of nucleic acids and protein synthesis leading an outstanding antichagasic action. Low water solubility and large therapeutic doses constitute the main problems to overcome in the development of dosage forms of this drug.

Light effect on the stability of β-lapachone in solution: pathways and kinetics of degradation.

Objectives: The purpose of this work was to study the chemical stability of the new antitumoral β-lapachone (βLAP) to determine the degradation pathway/s of the molecule and the degradation kinetics in addition to identifying several degradation products.

Method: Samples of βLAP in solution were stored under conditions of darkness and illumination at 40°C at which the pseudo-first order rate constants for the βLAP degradation were determined. Furthermore, drug degraded solutions were concentrated and purified using Sephadex LH-20 and preparative thin-layer chromatography and degradation products were identified by nuclear magnetic resonance spectroscopy.

Development of effervescent tablets containing benzonidazole complexed with cyclodextrin.

Objectives: Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD).

Method: In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ.

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease.

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease.

Dissolution rate enhancement of the novel antitumoral beta-lapachone by solvent change precipitation of microparticles.

beta-Lapachone [betaLAP] is a novel antitumor drug, which was recently on clinical trials with promising preliminary results. Problems derived from its low water solubility, its instability in solution and its high therapeutic dose constitute some challenges for pharmaceutical researchers. The purpose of the present work is to enhance the limited dissolution rate of betaLAP by the design of particles using a solvent change precipitation process.

Benznidazole.

THE CONFORMATION OF THE TITLE COMPOUND [SYSTEMATIC NAME: N-benzyl-2-(2-nitro-imidazol-1-yl)acetamide], C(12)H(12)N(4)O(3), can be described in terms of the relative orientation of three planar fragments, the imidazol group (A), benzyl group (B), and the acetamide fragment (C), with corresponding dihedral angles: A/C = 88.17 (4), B/C = 67.12 (5) and A/B = 21.

Characterization of beta-lapachone and methylated beta-cyclodextrin solid-state systems.

The purpose of this research was to explore the utility of beta cyclodextrin (betaCD) and beta cyclodextrin derivatives (hydroxypropyl-beta-cyclodextrin [HPbetaCD], sulfobutylether-beta-CD [SBbetaCD], and a randomly methylated-beta-CD [RMbetaCD]) to form inclusion complexes with the antitumoral drug, beta-lapachone (betaLAP), in order to overcome the problem of its poor water solubility. RMbetaCD presented the highest efficiency for betaLAP solubilization and was selected to develop solid-state binary systems. Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared (FTIR) and optical and scanning electron microscopy results suggest the formation of inclusion complexes by both freeze-drying and kneading techniques with a dramatic improvement in drug dissolution efficiency at 20-minute dissolution efficiency (DE(20-minute) 67.