Deformulation of a solid pharmaceutical form using computed tomography and X-ray fluorescence

Deformulation of medicines is of undeniable importance, since it can be utilized both to unravel the chemical composition of the excipients integrating a pharmaceutical formulation of a specific medicine and as an important tool to conduct morphometric studies of the formulation under study. Such strategy may be utilized in analytical studies aiming at quantifying the components of reference drugs, or in the identification of putative counterfeit pharmaceuticals. Deformulation makes use of physicochemical analysis tools to characterize, from the chemical point of view, the components integrating medicine pharmaceutical formulations and from the physical point of view, the morphological part of the pharmaceutical formulation. The techniques of computer tomography (SkyScan 1174 - Bruker microCT) and X-ray fluorescence analyses (using an X-ray source with W-anode from Hammatsu Photonics and Silicon Drift detector from Amptek) were successfully used in performing a process of deformulation of a solid pharmaceutical formulation of tablets, utilized herein as a model medicine for controlled drug release. The analytical methods used in this work, proved their effectiveness for the main goal of this study, which aimed to characterize a pharmaceutical formulation via its deconstruction.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brasil) (FAPESP Ref. No. 2012/15651-4, Tomógrafo para Aplicações na Área das Ciências Farmacêutica; FAPESP Ref. No. 2013/03181-6, Project PneumoPhageKill; FAPESP Ref. No. 2012/15651-4 and FAPESP Ref. No. 2013/19300-4, Auxílio à Pesquisa - Reserva Técnica para Infra-estrutura Institucional de Pesquisa) and by FINEP – Financiadora de Estudos e Projetos (FINEP, Rio de Janeiro, Brasil) (FINEP Ref. No. 01.13.0286.00

Development and characterization of a hydrogel containing nitrofurazone for antimicrobial topical applications

The goal of the research work entertained herein was the development and characterization of a poly-(vinyl alcohol) (PVA) hydrogel cross-linked with glutaraldehyde and impregnated with 0.2% (w/w) nitrofurazone (NTZ), for topical applications. To verify the active principle release capability, one has determined (i) swelling profile, (ii) in vitro release of NTZ via UV-VIS spectrophotometry, and (iii) antimicrobial activity via exposure to the hydrogel of ATCC strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The optimized hydrogel was further characterized via scanning electron microscopy (SEM), infrared spectroscopy with Fourier transform, moisture content determinations and thermal analyses via thermal gravimetry (TGA). Swelling tests revealed a mass increase from 100±5% up to 350±11%. Incorporated NTZ displayed bactericidal activity, as expected, being released in a linearly controlled fashion above 6 μg/mL during experiment timeframes of 14 h. SEM analyses allowed verification of a homogeneous surface morphology, while infrared spectra showed that NTZ did not bind strongly to the cross-linked polymer. Furthermore, results from thermal analyses suggested a loss of thermal stability arising from incorporation of NTZ in the hydrogel. The optimized hydrogel exhibited characteristics with high potential for (antimicrobial) treatment of skin lesions.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged. Sebastiao Coelho de Lima gratefully acknowledges financial support from the Centro Universitario da Barra Mansa (Rio de Janeiro/RJ, Brazil)

Characterization of a water-in-oil-in-water multiple emulsion integrating biomimetic aqueous-core lipid nanoballoons housing protein entities

Project funding by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) ( FAP ESP Ref. No. 2013/03181 - 6, Project PneumoPhageKill

Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence

"Available online 09 September 2016"Cigarette smoking is a serious public health problem. According to data from the World Health Organization, it is estimated that currently more than 1.2 billion people worldwide do tobacco use and that smoking-related diseases are responsible for about 6 million deaths each. With attention to this, it is necessary to seek preventive and prognostic of trying to reduce these numbers and alert the public in general about the danger and the harm caused by its use. Thus, the objective of the research work undertaken was to evaluate and compare the chemical composition of collected saliva samples of smokers and nonsmokers by X-ray Fluorescence analyses. 32 individuals were selected, 16 of which used cigarette on a daily basis and the other 16 had never smoked. Saliva was collected with the help of a (sterile) disposable Pasteur pipette and samples sent to the Applied Nuclear Physics Laboratory at UNISO (LAFINAU), where analyzes were carried out. Individuals who agreed to participate in the study answered a questionnaire to define their profile of inclusion and signed an informed consent form (CEP Protocol n° 831.753 of 09/10/2014). The results clearly showed that there are differences in the concentrations of chemical elements in the saliva of smokers and non-smokers. The biggest discrepancies were found at concentrations of the chemical elements Sulfur, Phosphorus, Chlorine and Potassium, and smaller differences in the concentration of the elements Calcium, Manganese, Iron, Copper, Titanium, Vanadium and Nickel. In only one saliva sample, and in quite low amounts, arsenic was detected. The results indicate that smoking produces more significant changes in the saliva of women than in men, increasing the concentration of some elements in the saliva of female smokers, much more than in the male smokers. The cigarette usage time also appears to exert a greater influence on the composition of the saliva of women than in men, indicating that the damage caused by cigarette use may in fact be higher in women than in men.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) (FAPESP Refs. no. 2012/ 15651-4 and 2013/03181-6)CNPq, National Council for Scientific and Technological Development – Brazil, in the form of Research Productivity (PQ) fellowships - Ref. no. 306113/2014-7, Ref. No. 309598/2014-

Zidovudine-poly(l-lactic acid) solid dispersions with improved intestinal permeability prepared by supercritical antisolvent process

A supercritical antisolvent (SAS) process for obtaining zidovudine-poly(l-lactic acid) (PLLA) solid dispersions (SDs) was used to attain a better intestinal permeation of this drug. A 32 factorial design was used, having as independent variables the ratio 3-azido-23-dideoxythymidine (AZT)PLLA and temperature/pressure conditions, as dependent variables the process yield and particle macroscopic morphology. AZTPLLA production batches were carried out by the SAS process, and the resulting products evaluated via scanning electron microscope, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared analyses. From the nine possible combinations of tests performed experimentally, only one combination did not produced a solid. The L3 batch of SD, produced with 1:2 (AZTPLLA) ratio, resulted in a 91.54% yield, with 40% AZT content. Intestinal permeability studies using the AZTPLLA from L3 batch led to an AZT permeability of approximately 9.87%, which was higher than that of pure AZT (3.84%). AZT remained in crystalline form, whereas PLLA remained in semicrystalline form. AZT release is controlled by a diffusion mechanism. It has been demonstrated that it is possible to use PLLA carrier and SAS process to obtain SD, in a single step.Cristalia (Itapira, Brazil) for the kind supply of the reference substance used throughout the research work. Financial support from Fundação de Amparo á Pesquisa do Estado de São Paulo (2013-19300-4; 2012/01333-0; 2011/21219-5), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PROSUP/CAPES) and Finep Inovação e Pesquisa (Finep, Brazil; 01.13.0286.00)

Development and characterization of a gel formulation integrating microencapsulated nitrofurazone

Nitrofurazone (NTZ) is usually employed in the topical treatment of infected wounds and lesions of both skin and mucosa. Microencapsulation is a process utilized in the incorporation of active ingredients within polymers aiming at, among other objectives, the prolonged release of pharmaceutical compounds and protection from atmospheric agents (viz. moisture, light, heat and/or oxidation). With the goal of utilizing the microparticles containing encapsulated NTZ in pharmaceutical formulations, one prepared microparticles containing NTZ via ionotropic gelation of sodium alginate. The microparticles were characterized via scanning electron microscopy analyses, Fourier transform infrared spectroscopy (FTIR) analyses, via determination of encapsulation efficiency, and via thermal analyses (both TGA and DSC). The final gel formulation was also characterized rheologically. The extrusion/solidification technique employed to obtain the calcium alginate microparticles with encapsulated NTZ was found to be adequate, and produced an NTZ encapsulation efficiency of ca. 97.8% ± 1.1%. The calcium alginate microparticles thus obtained, with encapsulated NTZ, exhibited an oval shape and hydrodynamic diameters between 500 μm and 800 μm. From the thermal analyses performed, together with information from the infrared spectra, one may conclude that NTZ did not strongly bind to the polymer, which may be favorable for the release of the active ingredient. From the results obtained in the present research effort, one may conclude that the microparticles produced possess the potential to be utilized as carriers for NTZ in pharmaceutical formulations such as gels, ointments, and solutions.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged

Chitosan-based scaffolds for tissue regeneration: preparation and microstructure characterization

Scaffolds are porous three-dimensional supports, designed to mimic the extracellular environment and remain temporarily integrated into the host tissue while stimulating, at the molecular level, specific cellular responses to each type of body tissues. The major goal of the research work entertained herein was to study the microstructure of scaffolds made from chitosan (Ch), blends of chitosan and sodium alginate (Ch/NaAlg), blends of chitosan, sodium alginate and calcium chloride (Ch/NaAlg/CaCl2) and blends of chitosan, sodium alginate and hydroxyapatite (Ch/NaAlg/HA). Scaffolds possessing ideal physicochemical properties facilitate cell proliferation and greatly increase the rate of recovery of a damaged organ tissue. Using CT three-dimensional images of the scaffolds, it was observed that all scaffolds had a porosity in the range 64%-92%, a radius of maximum pore occurrence in the range 95m-260m and a permeability in the range 1×10-10-18×10-10 m2. From the results obtained, the scaffolds based on Ch, Ch/NaAlg and Ch/NaAlg/CaCl2 would be most appropriate both for the growth of osteoid and for bone tissue regeneration, while the scaffold made with a blend of Ch/NaAlg/HA, by possessing larger pores size, might be used as a support for fibrovascular tissue.Project funding by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo, Brazil) (FAPESP Refs. No. 2012/21219-5, 2012/15651-4, 2013/03181-6, 2013/19300-4, and 2014/21122-0), is hereby gratefully acknowledged. This work received support from CNPq, National Council for Scientific and Technological Development – Brazil, in the form of Research Productivity (PQ) fellowships granted to Victor M. Balcão and Marco V. Chaud

Supercritical fluid and pharmaceutical applications. Part I: Process classification

The supercritical fluid technology has been target of many pharmaceuticals investigations in particles production for almost 35 years. This is due to the great advantages it offers over others technologies currently used for the same purpose. A brief history is presented, as well the classification of supercritical technology based on the role that the supercritical fluid (carbon dioxide) performs in the process.FAPESP (São Paulo, Brazil – project 2012/01333-0) for financial suppor

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part I: experimental factorial design

Lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water enclose, at least in theory, a biomimetic aqueous-core suitable for housing hydrophilic biomolecules such as proteins, peptides and bacteriophage particles. The research effort entertained in this paper reports a full statistical 23x31 factorial design study (three variables at two levels and one variable at three levels) to optimize biomimetic aqueous-core lipid nanoballoons for housing hydrophilic protein entities. The concentrations of protein, lipophilic and hydrophilic emulsifiers, and homogenization speed were set as the four independent variables, whereas the mean particle hydrodynamic size (HS), zeta potential (ZP) and polydispersity index (PI) were set as the dependent variables. The V23x31 factorial design constructed led to optimization of the higher (+1) and lower (-1) levels, with triplicate testing for the central (0) level, thus producing thirty three experiments and leading to selection of the optimized processing parameters as 0.015% (w/w) protein entity, 0.75% (w/w) lipophilic emulsifier (soybean lecithin) and 0.50% (w/w) hydrophilic emulsifier (poloxamer 188). In the present research effort, statistical optimization and production of protein derivatives encompassing full stabilization of their three-dimensional structure, has been attempted via housing said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion