Luciana A. Tacon

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°), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 µm. 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.

Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.

Paste Residence Time in a Spouted Bed Dryer. III: Effect of Paste Properties and Quality Interactions

The aim of this study was to evaluate the effects of paste properties on residence time during drying in a spouted bed dryer with inert bodies. The effect of paste solids content, surface tension, and viscosity on the residence time distribution and the mean residence times were studied using factorial experimental designs. The inert bodies used were glass and polyethylene beads. The mean residence times varied from 13.6 to 16.3 and 12.2 to 17.7 min for drying on glass and polyethylene beads, respectively. The analysis of variance showed that mean residence times significantly depended on solids content and surface tension for glass beads and also on viscosity for polyethylene beads. The residence time distributions for all conditions studied fitted well to the perfect mixing cell when applying the continuous stirred vessels in series model analysis. The powder density, flowability, and particle size depended on paste properties and inert type.

Paste Residence Time in a Spouted Bed Dryer. I: The Stimulus-Response Methodology

The stimulus response methodology was evaluated in an experimental study conducted to measure NaCl solution residence time distributions in a spouted bed dryer of inert particles. The influence of tracer volume, concentration, and injection mode upon the measured mean residence time and residence time distribution was determined following experimental design techniques. The injection mode showed no significant effect on residence times, whereas tracer volume and concentration had significant effects at the levels of 1 and 5%, respectively, under the conditions chosen initially. The steepest ascent and factorial design methods were applied to determine the range in parameters for optimum stimulus response. The procedure repeated for a polymeric paste showed similar results. However, the results also showed that care must be exercised when using the stimulus response technique and the optimum injection conditions must be determined. The procedure presented in this study may be adopted in future investigations of paste residence time distributions in spouted bed dryers of inert bodies.

Paste Residence Time in a Spouted Bed Dryer. IV: Effect of the Inert Particle Size Distribution

The residence time distribution and mean residence time of a 10% sodium bicarbonate solution that is dried in a conventional spouted bed with inert bodies were measured with the stimulus-response method. Methylene blue was used as a chemical tracer, and the effects of the paste feed mode, size distribution of the inert bodies, and mean particle size on the residence times and dried powder properties were investigated. The results showed that the residence time distributions could be best reproduced with the perfect mixing cell model or N = 1 for the continuous stirred tank reactor in a series model. The mean residence times ranged from 6.04 to 12.90 min and were significantly affected by the factors studied. Analysis of variance on the experimental data showed that mean residence times were affected by the mean diameter of the inert bodies at a significance level of 1% and by the size distribution at a level of 5%. Moreover, altering the paste feed from dripping to pneumatic atomization affected mean residence time at a 5% significance level. The dried powder characteristics proved to be adequate for further industrial manipulation, as demonstrated by the low moisture content, narrow range of particle size, and good flow properties. The results of this research are significant in the study of the drying of heat-sensitive materials because it shows that by simultaneously changing the size distribution and average size of the inert bodies, the mean residence times of a paste can be reduced by half, thus decreasing losses due to degradation.

Box-Behnken design to study the bergenin content and antioxidant activity of Endopleura uchi bark extracts obtained by dynamic maceration

Brazil has one of the worlds largest biodiversity in flora and a plant that has attracted attention is the Endopleura uchi (Huber) Cuatrec., Humiriaceae, which is native of the Brazilian Amazon. Among the many popular uses, this species is utilized in the treatment of womans genito urinary tract affections and also as anti-inflammatory. It is believed that their actions derive from the major constituent, bergenin. The objective of this work was to study the Endopleura uchi barks extraction using the dynamic maceration method and the effects of the extraction time, drug to solvent ratio and temperature. A Box-Behnken design was applied to study the influence of these factors and the respective response surfaces. The extract characterization was made by determination of its antioxidant activity by DPPH; total polyphenol content and bergenin content. In general, the extracts showed good antioxidant activity, with the IC50 ranging from 4.02 to 5.87 µg/mL. The polyphenol content ranged from 31.89 to 47.82%. High levels of chemical markers are observed in all extracts, with average bergenin content of 35.58%. The result showed that the multivariate study of extraction is key step in the development and standardization of extracts Endopleura uchi.