Victor Hugo Vitorino Sarmento

A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery.

The aim of the present work was to obtain an ophthalmic delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the treatment of ocular diseases. For this, an in situ forming gel comprised of the combination of a thermosetting polymer, poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) (PEO-PPO-PEO, poloxamer), with a mucoadhesive agent (chitosan) was developed. Different polymer ratios were evaluated by oscillatory rheology, texture and mucoadhesive profiles. Scintigraphy studies in humans were conduced to verify the retention time of the formulations developed. The results showed that chitosan improves the mechanical strength and texture properties of poloxamer formulations and also confers mucoadhesive properties in a concentration-dependent manner. After a 10-min instillation of the poloxamer/chitosan 16:1 formulation in human eyes, 50-60% of the gel was still in contact with the cornea surface, which represents a fourfold increased retention in comparison with a conventional solution. Therefore, the developed formulation presented adequate mechanical and sensorial properties and remained in contact with the eye surface for a prolonged time. In conclusion, the in situ forming gel comprised of poloxamer/chitosan is a promising tool for the topical treatment of ocular diseases.

Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system.

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity. Retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity. The aim of this study was the development, characterization and the in vivo effectiveness of RP in non-ionic LCS structures. LCS containing polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water in the ratio 30:10:60, with and without RP were studied. The results of the polarized light microscopy, small-angle X-ray scattering and rheology analysis indicated the presence of typical LCS structures with lamellar arrangement. Regardless of the presence of RP, the rheological studies showed the pseudo plastic behavior of the systems. However, highest hysteresis area was verified when comparing the system in the presence and in the absence of RP. Stability study SAXS monitored, carried out up to 30 days in various storage temperature conditions (25±2 °C, 37±2 °C and 5±2 °C) demonstrated the great structural stability of the LCS systems. The in vivo effectiveness analysis suggests that the RP-loaded LCS provided a significant reduction of the orbicular wrinkles in human volunteers (P=0.048).

Development and in vitro evaluation of surfactant systems for controlled release of zidovudine

The development of a controlled-release dosage form of zidovudine (AZT) is of crucial importance, in view of the pharmacokinetics of its toxic activity. A suitable drug delivery system could increase AZT bioavailability, reducing its dose-dependent side effects. In this study, systems composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol as surfactant (S), oleic acid as oil phase (O), and water (W) were developed, as possible AZT control release systems. They were characterized by polarized light microscopy (PLM), SAXS, and rheological analysis, followed by in vitro release assay. PLM and SAXS results indicated that the mixtures of S/O/W in the proportions 55/35/10 and 55/25/20 formed microemulsion (ME) systems, while 55/20/25 formed lamellar phase. The incorporation of AZT in these systems was greater than in water or oil; moreover, AZT incorporation did not significantly change the phase behavior of the mixtures. MEs behave as Newtonian fluids in flow rheological analysis and the lamellar phase as a pseudoplastic fluid. The release profile indicated that AZT could be released in a controlled manner, since an exponential pattern governs AZT diffusion, as demonstrated by the Weibull mathematical model. These systems are potential carriers for AZT and could have advantages over conventional pharmaceutical forms.

Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties

Objectives Zidovudine is the antiretroviral drug most frequently used for the treatment of AIDS. Although its effectiveness is recognized, it undergoes extensive first‐pass metabolism and exhibits poor oral bioavailability. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first‐pass effect. There are some mechanisms that limit intranasal absorption, such as mucociliary clearance, which rapidly removes the formulation from the nasal cavity. To improve the nasal residence time of zidovudine on the nasal mucosa, we aimed to develop a mucoadhesive surfactant system for zidovudine nasal administration.

Structure and viscoelastic behavior of pharmaceutical biocompatible anionic microemulsions containing the antitumoral drug compound doxorubicin

Structure and viscoelastic properties of negatively charged oil-in-water (o/w) microemulsions have been investigated. Microemulsions (ME) containing soya phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as surfactant, cholesterol (CHO) as oil phase, and aqueous buffer with and without the antitumoral doxorubicin (DOX) have been studied. The effect of the oil phase/surfactant ratio (O/S) and the DOX incorporation on the structural and rheological properties have been studied in several compositions of ME systems. The rheological analyses were performed through the oscillation stress sweep, creep recovery test, and viscosity test. The combination of the DOX incorporation with the high O/S ratio provided a further viscoelastic structure with linear behavior. Independently of the O/S ratio the oil phase diameter increases according to a sigmoid profile, stabilizing up to 340 min. The apparent viscosity decreases a minimum value with the shear rate, but increases with both the O/S ratio and the DOX incorporation in the system. The structural and rheological properties of the studied MEs were directly dependent on the O/S ratio and can be used to improve the application of the system in the pharmaceutical field.

Surfactant-based transdermal system for fluconazole skin delivery

The development of a controlled-release dosage form of antifungals is of crucial importance in view of the side-effects of conventional oral and intravenous treatments of Sporotrichosis. In this study, systems composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20) as a surfactant, oleic acid as an oil phase, and water were developed as a possible fluconazole transdermal drug delivery system. The systems were characterised by polarised light microscopy (PLM), SAXS, and rheological analysis, followed by cellular and histological analyses, in vitro release assays, and ex vivo skin permeation and retention studies using porcine ear tissue and a Franz diffusion cell. PLM and SAXS results indicated that the mixtures of surfactant, oil and water formed micellar and lamellar phases. The incorporation of fluconazole in these systems was greater than in water and conventional dosage forms. Micellar systems behave as Newtonian fluids, being more viscous than elastic in rheological analysis, and lamellar phases behave as pseudoplastic fluids with high elastic moduli. In vitro and in vivo biological assays showed that the formulations did not affect normal cell macrophages and did not promote skin irritation. The release profile indicated that fluconazole could be released in a controlled manner. It was found that the systems enhanced drug permeation and skin retention by changing only the composition of the components in the formulations. Therefore, PPG-5-CETETH-20- based systems have great potential as transdermal systems with different structural and rheological characteristics for Sporotrichosis treatment using antifungal drugs.

Characterization of Siloxane-poly(methyl methacrylate) Hybrid Films Obtained on a Tinplate Substrate Modified by the Addition of Organic and Inorganic Acids

Tinplate is used to food packaging and other types of packages. The corrosion resistance of the tinplate has been study due the necessity of an alternative to high environmental impact of chromatization process. Therefore protective coatings as hybrid films base elaborations with different acids are studied to improve the barrier effect against corrosion. The objective of this work is characterize hybrid films deposited on a tinplate from a sol made up of the alkoxide precursors 3-(trimethoxysilylpropyl)methacrylate (TMSM), tetraethoxysilane (TEOS) and poly(methyl methacrylate) (PMMA) together with one of three acids (acetic, hydrochloric or nitric acid) and to verify their action against the corrosion of the substrate. The films were obtained by a dip-coating process and cured for 3 hours at 160 °C. The film hydrophobicity was determined by contact angle measurements, and the morphology was evaluated by SEM. FTIR measurements were performed to characterize the chemical structures of the films. The electrochemical behavior of the coatings was evaluated by techniques open circuit potential monitoring (OCP), potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The results demonstrate that the siloxane-PMMA films improve the protective properties of the tinplate, with the films obtained by acetic acid addition exhibiting the greatest improvement.

Effect of Tetraethoxy-silane (TEOS) Amounts on the Corrosion Prevention Properties of Siloxane-PMMA Hybrid Coatings on Galvanized Steel Substrates

Siloxane-poly(methyl methacrylate) (PMMA) organic-inorganic hybrid coatings were deposited on galvanized steel by the dip-coating sol-gel technique. Anticorrosion properties, as well as the morphological, surface and structural features were studied. Hybrid coatings were synthesized from tetraethoxy-silane (TEOS) and methyl methacrylate (MMA) as inorganic and organic phases, respectively, linked by 3-metacriloxypropyl-trimethoxysilane (TMSM) as a coupling agent. The MMA/TMSM ratio was kept constant, whereas the four TEOS/TMSM ratios were varied. The characterization of coatings was assessed using several techniques such as Scanning Electronic Microscopy (SEM), Contact Angle, Fourier Transform Infrared (FT-IR), Open Circuit Polarization (OCP), Atomic Force Microscopy (AFM) and Electrochemical Impedance Spectroscopy measurements (EIS). The EIS results, which were obtained for the hybrid coatings, were discussed based on an electrical equivalent circuit used to adjust the experimental data. The results showed that the increasing the TEOS content caused increase in coating thickness, increased in the surface roughness and increased in the surface hydrophobicity. The film with the highest TEOS content presented the best electrochemical performance, more effective in protecting against corrosion.

A new functionalized MCM-41 mesoporous material for use in environmental applications

Este trabalho descreve a sintese e caracterizacao de um novo adsorvente mesoporoso que consiste o MCM-41 funcionalizado com o acido p-aminobenzoico modificado (PABA-Si). A sintese foi realizada pelo metodo hidrotermal/co-condensacao. O PABA-MCM-41 foi caracterizado usando FTIR, SAXS, adsorcao/desorcao de N2, MEV e TG. Os experimentos em batelada foram utilizados para determinar os efeitos da concentracao inicial do adsorbato, tempo de contato e temperatura. A adsorcao do benzo[a]pireno (B[a]P) alcancou o equilibrio depois de 90 min (qe = 27,2 µg g-1) e concentracoes mais altas do adsorbato foram associadas com o aumento, em ambos, da percentagem de remocao (71,0-95,7%) e no valor de qe (20,1-27,1 µg g-1). A adsorcao seguiu o modelo cinetico de pseudo-segunda ordem, e se ajustou ao modelo de isoterma de Langmuir. Foi verificado em temperaturas mais altas um aumento na taxa inicial de adsorcao e na constante cinetica. Os parâmetros termodinâmicos indicaram que o processo foi espontâneo, endotermico e com uma tendencia para desordem.

Compatibility study of hydroxypropylmethylcellulose films containing zidovudine and lamivudine using thermal analysis and infrared spectroscopy

Zidovudine (AZT) and lamivudine (3TC) are drugs commonly used in the treatment of acquired immune deficiency syndrome; however, these drugs have low bioavailability and short biological half-life. These factors contribute to the emergence of various side effects and lack of patient adherence to treatment. Therefore, the study of drug delivery systems is of extreme interest. In this context, this study intends to develop hydroxypropylmethylcellulose films (HPMC) containing AZT and films containing 3TC, and assess the existence of drug/polymer interactions by means of thermal analysis techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)/derivative TG (DTG)], Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD), contributing to the optimization of antiretroviral therapy. The films produced showed drying uniformity and drug distribution. DSC curves indicated that these drugs may be in an amorphous form dispersed in the polymeric matrix. Thermal decomposition profiles obtained in the TG/DTG studies of films containing drugs showed similarities with the curves of their respective physical mixtures. The FTIR spectra showed the characteristic bands conservation of AZT and 3TC isolated in the films with drugs. The results indicate that these drugs did not undergo a process of degradation or chemical interaction with the polymer that would lead to the modification or alteration of their chemical structures. XRD studies confirmed that these drugs were homogenously dispersed in the polymeric matrix. These results also showed that there was no drug/polymer incompatibility in HPMC films.