Thermal analysis of biodegradable microparticles containing ciprofloxacin hydrochloride obtained by spray drying technique

Thermal analysis has been extensively used to obtain information about drug-polymer interactions and to perform pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles of poly(D,L-lactide-co-glycolide) (PLGA) containing ciprofloxacin hydrochloride (CP) in various drug:polymer ratios were obtained by spray drying. The main purpose of this study was to investigate the effect of the spray drying process on the drug-polymer interactions and on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG) and infrared spectroscopy (IR). The results showed that the high levels of encapsulation efficiency were dependant on drug:polymer ratio. DSC and TG/DTG analyses showed that for physical mixtures of the microparticles components the thermal profiles were different from those signals obtained with the pure substances. Thermal analysis data disclosed that physical interaction between CP and PLGA in high temperatures had occurred. The DSC and TG profiles for drug-loaded microparticles were very similar to the physical mixtures of components and it was possible to characterize the thermal properties of microparticles according to drug content. These data indicated that the spray dryer technique does not affect the physicochemical properties of the microparticles. In addition, the results are in agreement with IR data analysis demonstrating that no significant chemical interaction occurs between CP and PLGA in both physical mixtures and microparticles. In conclusion, we have found that the spray drying procedure used in this work can be a secure methodology to produce CP-loaded microparticles. (C) 2007 Elsevier B.V. All rights reserved.

Yerba Mate (Ilex paraguariensis) Aqueous Extract Decreases Intestinal SGLT1 Gene Expression but Does Not Affect Other Biochemical Parameters in Alloxan-Diabetic Wistar Rats

Yerba mate (Ilex paraguariensis) is rich in polyphenols, especially chlorogenic acids. Evidence suggests that dietary polyphenols could play a role in glucose absorption and metabolism. The aim of this study was to evaluate the antidiabetic properties of yerba mate extract in alloxan-induced diabetic Wistar rats. Animals (n = 41) were divided in four groups: nondiabetic control (NDC, n = 10), nondiabetic yerba mate (NDY, n = 10), diabetic control (DC, n = 11), and diabetic yerba mate (NDY, n = 10). The intervention consisted in the administration of yerba mate extract in a 1 g extract/kg body weight dose for 28 days; controls received saline solution only. There were no significant differences in serum glucose, insulin, and hepatic glucose-6-phosphatase activity between the groups that ingested yerba mate extract (NDY and DY) and the controls (NDC and DC). However, the intestinal SGLT1 gene expression was significantly lower in animals that received yerba mate both in upper (p = 0.007) and middle (p < 0.001) small intestine. These results indicate that bioactive compounds present in yerba mate might be capable of interfering in glucose absorption, by decreasing SGLT1 expression.

Assessment of production efficiency, physicochemical properties and storage stability of spray-dried chlorophyllide, a natural food colourant, using gum Arabic, maltodextrin and soy protein isolate-based carrier systems

P>The aim of this research was to study spray drying as potential action to protect chlorophyllide from environmental conditions for shelf-life extension and characterisation of the powders. Six formulations were prepared with 7.5 and 10 g of carrier agents [gum Arabic (GA), maltodextrin (MA) and soybean protein isolate (SPI)]/100 mL of chlorophyllide solutions. The powders were evaluated for morphological characteristics (SEM), particle size, water activity, moisture, density, hygroscopicity, cold water solubility, sorption isotherms, colour and stability, during 90 days. All the powders were highly soluble, with solubility values around 97%. A significant lower hygroscopicity was observed for GA powders, whilst the lower X(m) values obtained by GAB equation fitting of the sorption isotherms was observed for the 7.5 g MA/100 mL samples. All formulations, but the 1 (7.5 g SPI/100 mL of chlorophyllide), provided excellent stability to the chlorophyllide during 90 days of storage even at room temperature.

Selection of operational parameters for the production of instant soy protein isolate by pulsed fluid bed agglomeration

The objective of this study was to select the optimal operational conditions for the production of instant soy protein isolate (SPI) by pulsed fluid bed agglomeration. The spray-dried SPI was characterized as being a cohesive powder, presenting cracks and channeling formation during its fluidization (Geldart type A). The process was carried out in a pulsed fluid bed, and aqueous maltodextrin solution was used as liquid binder. Air pulsation, at a frequency of 600 rpm, was used to fluidize the cohesive SPI particles and to allow agglomeration to occur. Seventeen tests were performed according to a central composite design. Independent variables were (i) feed flow rate (0.5-3.5 g/min), (ii) atomizing air pressure (0.5-1.5 bar) and (iii) binder concentration (10-50%). Mean particle diameter, process yield and product moisture were analyzed as responses. Surface response analysis led to the selection of optimal operational parameters, following which larger granules with low moisture content and high process yield were produced. Product transformations were also evaluated by the analysis of size distribution, flowability, cohesiveness and wettability. When compared to raw material, agglomerated particles were more porous and had a more irregular shape, presenting a wetting time decrease, free-flow improvement and cohesiveness reduction. (C) 2010 Elsevier B.V. All rights reserved.

The use of spray drying technology to reduce bitter taste of casein hydrolysate

The utilization of protein hydrolysates in food systems is frequently hindered due to their bitterness and hygroscopicity. Spray drying technology could be an alternative for reducing these problems. The aim of this work was to reduce or to mask the casein hydrolysate bitter taste using spray drying and mixtures of gelatin and soy protein isolate (SPI) as carriers. Six formulations were studied: three with 20% of hydrolysate and 80% of mixture (gelatine/SPI at proportions of 50/50, 40/60 and 60/40%) and three with 30% of hydrolysate and 70% of mixture (gelatine/SPI at proportions of 50/50, 40/60 and 60/40%). The spray-dried formulations were evaluated by SEM, hygroscopicity, thermal behavior (DSC), dissolution, and bitter taste, by a trained sensory panel using a paired-comparison test (free samples vs. spray-dried samples); all samples were presented in powder form. SEM analysis showed mostly spherically shaped particles, with many concavities and some particles with pores. All formulations were oil and water compatible and showed lower hygroscopicity values than free casein hydrolysate. At Aw 0.83, the free hydrolysate showed Tg about 25 degrees C lower than the formulations, indicating that the formulations may be more stable at Aw >= 0.65 since the glass transition should be prevented. The sensory panel found the formulations, tasted in the powder form, to be less bitter (P < 0.05) than the free casein hydrolysate. These results indicated that spray drying of casein hydrolysate with mixtures of gelatin and SPI was successful to attenuate the bitterness of casein hydrolysate. Thus, spray drying widens the possibilities of application of casein hydrolysates. (C) 2009 Elsevier Ltd. All rights reserved.

Production and properties of casein hydrolysate microencapsulated by spray drying with soybean protein isolate

The aim of this work was to encapsulate casein hydrolysate by spray drying with soybean protein isolate (SPI) as wall material to attenuate the bitter taste of that product. Two treatments were prepared: both with 12 g/100 g solids and containing either two proportions of SPI: hydrolysate (70:30 and 80:20), called M1 and M2, respectively. The samples were evaluated for morphological characteristics (SEM), particle size, hygroscopicity, solubility, hydrophobicity, thermal behavior and bitter taste with a trained sensory panel using a paired-comparison test (non-encapsulated samples vs. encapsulated samples). Microcapsules had a continuous wall, many concavities, and no porosity. Treatments M1 and M2 presented average particle sizes of 11.32 and 9.18 mu m, respectively. The wall material and/or the microencapsulation raised the hygroscopicity of the hydrolysate since the free hydrolysate had hygroscopicity of 53 g of water/100 g of solids and M1 and M2 had 106.99 and 102.19 g of water/100 g of solids, respectively. However, the hydrophobicity decreases, the absence of a peak in encapsulated hydrolysates, and the results of the panel sensory test considering the encapsulated samples less bitter (p < 0.05) than the non-encapsulated, showed that spray drying with SPI was an efficient method for microencapsulation and attenuation of the bitter taste of the casein hydrolysate. (c) 2008 Elsevier Ltd. All rights reserved.

Physical properties of goat milk powder with soy lecithin added before spray drying

P>In this study, physical characteristics of goat milk powder produced with the addition of soy lecithin at levels of 0 (control), 0.4, 0.8 and 1.0 g lecithin/100 g of total solids in concentrated milk before the spray drying process were investigated. Goat milk was pasteurised, concentrated at 40% of total solids, spray dried and packed in plastic bags under vaccum conditions. Lecithin addition decreased the wetting time of milk powders, although no influence was observed on dispersibility, water sorption, water activity and particle size distribution of the powders. Powders with higher levels of lecithin showed significantly lower brightness, with a greater intensity of yellow colour. It was concluded that lecithin addition before spray drying process at the minimal proportion in concentrated milk of 0.4 g lecithin/100 g of total solids in concentrated milk is useful for achieving more rapid wetting time of goat milk powder.

Objective Assessment of Internal Nasal Dimensions and Speech Resonance in Individuals With Repaired Unilateral Cleft Lip and Palate After Rhinoseptoplasty

The objective of the current study was to analyze the effects of rhinoseptoplasty on internal nasal dimensions and speech resonance of individuals with unilateral cleft lip and palate, estimated by acoustic rhinometry and nasometry, respectively. Twenty-one individuals (aged 15-46 years) with previously repaired unilateral cleft lip and palate were analyzed before (PRE), and 6 to 9 (POST1) and 12 to 18 months (POST2) after surgery. Acoustic rhinometry was used to measure the cross-sectional areas (CSAs) of segments corresponding to the nasal valve (CSA1), anterior portion (CSA2), and posterior portion (CSA3) of the lower turbinate, and the volumes at the nasal valve (V1) and turbinate (V2) regions at cleft and noncleft sides, before and after nasal decongestion with a topical vasoconstrictor. Nasometry was used to evaluate speech nasalance during the reading of a set of sentences containing nasal sounds and other devoid of nasal sounds. At the cleft side, before nasal decongestion, there was a significant increase (P < 0.05) in mean CSA1 and V1 values at POST1 and POST2 compared with PRE. After decongestion, increased values were also observed for CSA2 and V2 at POST2. No significant changes were observed at the noncleft side. Mean nasalance values at PRE, POST1, an POST2 were not different from each other in both oral and nasal sentences. The measurement of CSAs and volumes by acoustic rhinometry revealed that rhinoseptoplasty provided, in most cases analyzed, a significant increase in nasal patency, without concomitant changes in speech resonance, as estimated by nasalance assessment.

Serological response of guinea pigs to oily and aqueous inactivated vaccines containing a Brazilian isolate of the Bovine Viral Diarrhea Virus (BVDV)

Bovine Viral Diarrhea Virus (BVDV) is widespread in cattle in Brazil and research shows its large antigenic variability. Available vaccines are produced with virus strains isolated in other countries and may not be effective. In this study, inactivated vaccines containing the Brazilian BVDV-Ib IBSP11 isolate were developed and tested on 6 groups of 10 guinea pigs (Cavia porcellus). Animals in groups A and C received an aqueous vaccine (aluminum hydroxide); B and D groups received an oily vaccine (Montanide ISA50); Group E positive-control animals were given an imported commercial vaccine with BVDV-la Singer; Group F animals were sham vaccinated (negative control). Groups A, B and E received two doses, and Groups C and D, three, every 21 days. Twelve blood samples were taken, at 21-day intervals over 231 days, and evaluated for antibody titer through virus-neutralization (VN), using a homologous strain (IBSP11), and a heterologous strain (BVDV-la NADL). Most animals, 42 days following the first dose, seroconverted to both strains and, after the second dose, there was a significant increase of titers in all groups. The oily formulation induced greater response after the third administration. This increase was not observed with the aqueous vaccines, regardless of the virus used in the VN. Antibody decline was more rapid in animals that received aqueous vaccines. The results showed the importance of studying the influence of endemic strains of commercial vaccines, to improve the efficacy of BVD vaccination. Use of the endemic strain in vaccine formulation presented promising results, as well as the use of guinea pigs as a laboratory model. (C) 2011 Elsevier Ltd. All rights reserved.

Continuum, Discrete, and Explicit Solvation Models for Describing the Low-Lying Absorption Spectrum of the Pterin Acid in Aqueous Environment

The absorption spectrum of the acid form of pterin in water was investigated theoretically. Different procedures using continuum, discrete, and explicit models were used to include the solvation effect on the absorption spectrum, characterized by two bands. The discrete and explicit models used Monte Carlo simulation to generate the liquid structure and time-dependent density functional theory (B3LYP/6-31G+(d)) to obtain the excitation energies. The discrete model failed to give the correct qualitative effect on the second absorption band. The continuum model, in turn, has given a correct qualitative picture and a semiquantitative description. The explicit use of 29 solvent molecules, forming a hydration shell of 6 angstrom, embedded in the electrostatic field of the remaining solvent molecules, gives absorption transitions at 3.67 and 4.59 eV in excellent agreement with the S(0)-S(1) and S(0)-S(2) absorption bands at of 3.66 and 4.59 eV, respectively, that characterize the experimental spectrum of pterin in water environment. (C) 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110: 2371-2377, 2010

Thermal Phase Behavior of DMPG Bilayers in Aqueous Dispersions as Revealed by (2)H- and (31)P-NMR

The synthetic lipid 1,2-dimyristoyl-sn-3-phosphoglycerol (DMPG), when dispersed in water/NaCl exhibits a complex phase behavior caused by its almost unlimited swelling in excess water. Using deuterium ((2)H)- and phosphorus ((31)P)-NMR we have studied the molecular properties of DMPG/water/NaCl dispersions as a function of lipid and NaCl concentration. We have measured the order profile of the hydrophobic part of the lipid bilayer with deuterated DMPG while the orientation of the phosphoglycerol headgroup was deduced from the (31)P NMR chemical shielding anisotropy. At temperatures > 30 degrees C we observe well-resolved (2)H- and (31)P NMR spectra not much different from other liquid crystalline bilayers. From the order profiles it is possible to deduce the average length of the flexible fatty acyl chain. Unusual spectra are obtained in the temperature interval of 20-25 degrees C, indicating one or several phase transitions. The most dramatic changes are seen at low lipid concentration and low ionic strength. Under these conditions and at 25 degrees C, the phosphoglycerol headgroup rotates into the hydrocarbon layer and the hydrocarbon chains show larger flexing motions than at higher temperatures. The orientation of the phosphoglycerol headgroup depends on the bilayer surface charge and correlates with the degree of dissociation of DMPG-Na(+). The larger the negative surface charge, the more the headgroup rotates toward the nonpolar region.

Solvent Effects in Chemical Processes. Water-Assisted Proton Transfer Reaction of Pterin in Aqueous Environment

Pterins are members of a family of heterocyclic compounds present in a wide variety of biological systems and may exist in two forms, corresponding to an acid and a basic tautomer. In this work, the proton transfer reaction between these tautomeric forms was investigated in the gas phase and in aqueous solution. In gas phase, the intramolecular mechanism was carried out for die isolated pterin by quantum mechanical second-order Moller-Plesset Perturbation theory (MP2/aug-cc-pVDZ) calculations and it indicates that the acid form is more stable than the basic form by -1.4 kcal/mol with a barrier of 34.2 kcal/mol with respect to the basic form. In aqueous solution, the role of the water molecules in the proton transfer reaction was analyzed in two separated parts, the direct participation of one water molecule in the reaction path, called water-assisted mechanism, and the complementary participation of the aqueous solvation. The water-assisted mechanism was carried out for one pterin-water cluster by quantum mechanical calculations and it indicates that the acid form is still more stable by -3.3 kcal/mol with a drastic reduction of 70% of the barrier, The bulk solution effect on the intramolecular and water-assisted mechanisms was included by free energy perturbation implemented on Monte Carlo simulations. The bulk water effect is found to be substantial and decisive when the reaction path involves the water-assisted mechanism. In this case, the free energy barrier is only 6.7 kcal/mol and the calculated relative Gibbs free energy for the two tautomers is -11.2 kcal/mol. This value is used to calculate the pK(a) value of 8.2 +/- 0.6 that is in excellent agreement with the experimental result of 7.9.

Specific surface area and structures of aluminas from fibrillar pseudoboehmite

By heating powders of the aluminum monohydroxide fibrillar pseudoboehmite from 200 degrees C to 1400 degrees C several high surface area aluminas are prepared and characterized by X-ray diffraction and electron optical methods. Aqueous sols with pseudoboehmite fibrils of different lengths were dried by two methods: at room temperature and spray-dried. The following aluminas were obtained after treatment of the powders at increasing temperatures and having a range of specific surface areas: gamma-Al(2)O(3) (470 degrees C - 770 degrees C; 179 m(2)/g 497 m(2)/g); delta-Al(2)O(3) (770 degrees C - 930 degrees C; 156 m(2)/g - 230 m(2)/g); theta-Al(2)O(3) (930 degrees C - 1050 degrees C; 11 m(2)/g - 200 m(2)/g); alpha-Al(2)O(3) (1050 degrees C - 1400 degrees C; 2 m(2)/g - 17 m(2)/g). Spray-dried powders, fired at the same temperature than the ground powders, showed higher specific surface areas. The higher surface area alumina have values of the same order of magnitude of the commercial ""ad-cat"" aluminas.

First evidence of crystalline KHSO(4):Mn grown by an aqueous solution method and the investigation of the effect of ionizing radiation exposure

In this work, KHSO(4):Mn crystals doped with Mn and K(2)SO(4) were synthesized using an aqueous solution method. The samples were exposed to ionizing radiation in order to observe the effects on their physical properties. Raman spectroscopy was used to identify the structure of the crystals by detecting the vibrational frequencies of the crystalline lattice. Electron paramagnetic resonance (EPR) was used to study the creation of paramagnetic centers arising from exposure to ionizing radiation. This new synthesis method produces high quality K(2)SO(4) and KHSO(4):Mn crystals and allows control of structural, morphological, optical and magnetic properties. (C) 2009 Elsevier B.V. All rights reserved,

Phototransformation of hematoporphyrin in aqueous solution: Anomalous behavior at low oxygen concentration

The photoactivation of a photosensitizer is the initial step in photodynamic therapy (PDT) where photochemical reactions result in the production of reactive oxygen species and eventually cell death. In addition to oxidizing biomolecules, some of these photochemical reactions lead to photosensitizer degradation at a rate dependent on the oxygen concentration among other factors. We investigated photodegradation of Photogem A (R) (28 mu M), a hematoporphyrin derivative, at different oxygen concentrations (9.4 to 625.0 mu M) in aqueous solution. The degradation was monitored by fluorescence spectroscopy. The degradation rate (M/s) increases as the oxygen concentration increases when the molar ratio of oxygen to PhotogemA (R) is greater than 1. At lower oxygen concentrations (< 25 mu M) an inversion of this behavior was observed. The data do not fit a simple kinetic model of first-order dependence on oxygen concentration. This inversion of the degradation rate at low oxygen concentration has not previously been demonstrated and highlights the relationship between photosensitizer and oxygen concentrations in determining the photobleaching mechanism(s). The findings demonstrate that current models for photobleaching are insufficient to explain completely the effects at low oxygen concentration.