Spray Congealing of Pharmaceuticals: Study on Production of Solid Dispersions Using Box-Behnken Design

This work aimed at evaluating the spray congealing method for the production of microparticles of carbamazepine combined with a polyoxylglyceride carrier. In addition, the influence of the spray congealing conditions on the improvement of drug solubility was investigated using a three-factor, three-level Box-Behnken design. The factors studied were the cooling air flow rate, atomizing pressure, and molten dispersion feed rate. Dependent variables were the yield, solubility, encapsulation efficiency, particle size, water activity, and flow properties. Statistical analysis showed that only the yield was affected by the factors studied. The characteristics of the microparticles were evaluated using X-ray powder diffraction, scanning electron microscopy, differential scanning calorimetry, and hot-stage microscopy. The results showed a spherical morphology and changes in the crystalline state of the drug. The microparticles were obtained with good yields and encapsulation efficiencies, which ranged from 50 to 80% and 99.5 to 112%, respectively. The average size of the microparticles ranged from 17.7 to 39.4 mu m, the water activities were always below 0.5, and flowability was good to moderate. Both the solubility and dissolution rate of carbamazepine from the spray congealed microparticles were remarkably improved. The carbamazepine solubility showed a threefold increase and dissolution profile showed a twofold increase after 60 min compared to the raw drug. The Box-Behnken fractional factorial design proved to be a powerful tool to identify the best conditions for the manufacture of solid dispersion microparticles by spray congealing.

Optimization of in situ derivatization SPME by experimental design for GC-MS multi-residue analysis of pharmaceutical drugs in wastewater

This paper presents the development of a procedure, which enables the analysis of nine pharmaceutical drugs in wastewater using gas chromatography-mass spectrometry (GC-MS) associated with solid-phase microextraction (SPME) for the sample preparation. Experimental design was applied to optimize the in situ derivatization and the SPME extraction conditions. Ethyl chloroformate (ECF) was employed as derivatizing agent and polydimethylsiloxane-divinylbenzene (PDMS-DVB) as the SPME fiber coating. A fractional factorial design was used to evaluate the main factors for the in situ derivatization and SPME extraction. Thereafter, a Doehlert matrix design was applied to find out the best experimental conditions. The method presented a linear range from 0.5 to 10 mu g/L, and the intraday and interday precision were lower than 16%. Applicability of the method was verified from real influent and effluent samples of a wastewater treatment plant, as well as from samples of an industry wastewater and a river.

Influence of temperature, light and nutrients on the growth rates of the macroalga Gracilaria domingensis in synthetic seawater using experimental design

In the present study, the daily relative growth rates (DRGR, in percent per day) of the red macroalga Gracilaria domingensis in synthetic seawater was investigated for the combined influence of five factors, i.e., light (L), temperature (T), nitrate (N), phosphate (P), and molybdate (M), using a statistical design method. The ranges of the experimental cultivation conditions were T, 18-26A degrees C; L, 74-162 mu mol photons m(-2) s(-1); N, 40-80 mu mol L-1; P, 8-16 mu mol L-1; and M, 1-5 nmol L-1. The optimal conditions, which resulted in a maximum growth rate of a parts per thousand yen6.4% d(-1) from 7 to 10 days of cultivation, were determined by analysis of variance (ANOVA) multivariate factorial analysis (with a 2(5) full factorial design) to be L, 74 mu mol photons m(-2) s(-1); T, 26A degrees C; N, 80 mu mol L-1; P, 8 mu mol L-1; and M, 1 nmol L-1. In additional, these growth rate values are close to the growth rate values in natural medium (von Stosch medium), i.e., 6.5-7.0% d(-1). The results analyzed by the ANOVA indicate that the factors N and T are highly significant linear terms, X (L), (alpha = 0.05). On the other hand, the only significant quadratic term (X (Q)) was that for L. Statistically significant interactions between two different factors were found between T vs. L and N vs. T. Finally, a two-way (linear/quadratic interaction) model provided a quite reasonable correlation between the experimental and predicted DRGR values (R (adjusted) (2) = 0.9540).

Determination of Opiates in Whole Blood and Vitreous Humor: A Study of the Matrix Effect and an Experimental Design to Optimize Conditions for the Enzymatic Hydrolysis of Glucuronides

Faculty of Medicine University of Sao Paulo

Diferentes fontes e níveis de selênio sobre a imunidade humoral de frangos de corte

The use of organic trace minerals is getting strength and is an alternative to increase production and improve other characteristics such as humoral immunity. The present study was conducted to evaluate the effect of different levels and sources of selenium (Se) on humoral immunity of broilers. A six-week research was conducted using 1440 one-day-old males broiler chickens. The experimental design was randomized with six experimental diets (A: 0.15mg kg(-1) inorganic (inorg.); B: 0.15mg kg(-1) organic; C: 0.15mg kg(-1) inorg. + organic; D: 0.45mg kg(-1) inorganic; E: 0.45mg kg(-1) organic; F: 0.45mg kg(-1) inorg. + organic) calculated to provide the described amount of Se. Each diet was replicated in six box with 40 birds. A 3x2 factorial arrangement was used and the data were analyzed by ANOVA. The immunity was evaluated by means of the reaction against vaccine of Newcastle disease, and a reaction against sheep red blood cells (SRBC). No significant effects were observed at 5% significance level in NewCastle antibody (P >0.05). However at 14 day-old the source factor had p value at 0.0580, that show a trend of inorganic source in prolong the maternal immunity. No effect was observed in the immune response against SRBC (P >0.05). The results showed a immunologic response against Newcastle vaccine and SRBC, but the treatments was not able to induce a significant difference. The source and the level of Se showed no effect on the response against Newcastle vaccine and SRBC.

Microparticulated Hydrochlorothiazide Solid Dispersion: Enhancing Dissolution Properties via Spray Drying

The aim of the present study was to obtain microparticles of hydrochlorothiazide, a diuretic drug that practically insoluble in water, by spray drying and to investigate the influence of process parameters using a three-level, three-factor Box-Behnken design. Process yields, moisture content, particle size, flowability, and solubility were used to evaluate the spray-dried microparticles. The data were analyzed by response surface methodology using analysis of variance. The independent variables studied were outlet temperature, atomization pressure, and drug content. The formulations were prepared using polyvinylpyrrolidone and colloidal silicon dioxide as the hydrophilic carrier and drying aid, respectively. The microparticle yield ranged from 18.15 to 59.02% and resulted in adequate flow (17 to 32 degrees), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 mu m. The analysis of variance showed that the factors studied influenced the yields, moisture content, angle of repose, and solubility. Thermal analysis and X-ray diffractometry evidenced no drug interactions or chemical modifications. Photomicrographs obtained by scanning electron microscopy showed spherical particles. The solubility and dissolution rates of hydrochlorothiazide were remarkably improved when compared with pure drug. Therefore, the results confirmed the high potential of the spray-drying technique to obtain microparticulate hydrochlorothiazide with enhanced pharmaceutical and dissolution properties.

The double task of preventing malnutrition and overweight: a quasi-experimental community-based trial

Background: The Maternal-Child Pastoral is a volunteer-based community organization of the Dominican Republic that works with families to improve child survival and development. A program that promotes key practices of maternal and child care through meetings with pregnant women and home visits to promote child growth and development was designed and implemented. This study aims to evaluate the impact of the program on nutritional status indicators of children in the first two years of age. Methods: A quasi-experimental design was used, with groups paired according to a socioeconomic index, comparing eight geographical areas of intervention with eight control areas. The intervention was carried out by lay health volunteers. Mothers in the intervention areas received home visits each month and participated in a group activity held biweekly during pregnancy and monthly after birth. The primary outcomes were length and body mass index for age. Statistical analyses were based on linear and logistic regression models. Results: 196 children in the intervention group and 263 in the control group were evaluated. The intervention did not show statistically significant effects on length, but point estimates found were in the desired direction: mean difference 0.21 (95%CI −0.02; 0.44) for length-for-age Z-score and OR 0.50 (95%CI 0.22; 1.10) for stunting. Significant reductions of BMI-for-age Z-score (−0.31, 95%CI −0.49; -0.12) and of BMI-for-age > 85th percentile (0.43, 95%CI 0.23; 0.77) were observed. The intervention showed positive effects in some indicators of intermediary factors such as growth monitoring, health promotion activities, micronutrient supplementation, exclusive breastfeeding and complementary feeding. Conclusions: Despite finding effect measures pointing to effects in the desired direction related to malnutrition, we could only detect a reduction in the risk of overweight attributable to the intervention. The findings related to obesity prevention may be of interest in the context of the nutritional transition. Given the size of this study, the results are encouraging and we believe a larger study is warranted.