Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability

Solid dispersions are defined as dispersions of one or more active pharmaceutical ingredients in inert solid-state carriers. They are made with the aim to increase solubility and the dissolution rate of low solubility active pharmaceutical ingredients, with the subsequent increase in their bioavailability. The aim of this study was the development and optimization of solid dispersion formulations with carbamazepine, using D-optimal experimental design, in order to increase the dissolution rate of the selected model drug. By using the method of experimental mixture design, solid dispersions were formulated by varying the ratio of carbamazepine (30-50 %), Gelucire? 44/14 (20-40 %) and Soluplus? polymer (30-50 %) (input parameters). Sixteen formulations were made and used for in vitro testing of the carbamazepine dissolution rate. The observed output parameters were the percentages of carbamazepine released after 10, 20, 30, 45, and 60 minutes. After the data analysis, three test formulations were chosen from different parts of the optimization area. They were prepared and the carbamazepine dissolution rate was determined, followed by stability assessment for 24 months under ambient conditions (25?C, 40 % RH). The highest dissolution rate of carbamazepine from solid dispersions (more than 80 % in 30 minutes) was achieved at the carbamazepine mass fraction of about 40 %, Soluplus? of about 45 % and Gelucire? 44/14 of about 25 %. Comparing the predicted and the experimental obtained release rate profiles of carbamazepine from the three prepared optimized formulations, a significant compliance of the results was observed (f1<15; f2>50). The application of the PAMPA (Parallel Artificial-Membrane Permeability Assay) test has shown that carbamazepine premeability was maintained and mildly increased in two out of the three tested optimzed solid state formulations. Raman spectroscopy, FT-IR and DSC analyes showed that in the three optimized solid dispersions, after preparation and 24 months of storage, interactions between carbamazepine and the excipients were not present and that carbamazepine remained in the single pharmacologically active crystal polymorph form III. Proper selection of solid dispersion proportions of carbamazepine, Gelucire? 44/14 and Soluplus? may significantly increase the dissolution rate of the active substance, and the method of experimental mixture design can be successfully used for optimization of these formulations.

In His Element

Some of Burnett’s most characteristic and impressive work has taken the form of completely independent, very low budget short films that he has written, directed, photographed, and edited. These films return him to his beginnings as a sort of guerilla filmmaker who works in the streets. This chapter gives three examples: When It Rains (1995), a jazz fable about a neighborhood griot who tries to keep a mother and daughter from being evicted; The Final Insult (1997), an experimental mixture of documentary and fiction concerning homelessness in Los Angeles; and Quiet As Kept, a darkly comic film about a black family that has been displaced by Hurricane Katrina. The chapter ends with a comment on Burnett’s work in progress and his continuing importance for us today.

EVALUATION OF REVEGETATION TECHNIQUES FOR ROADSIDE CONSTRUCTION SITES

Vegetation is often used to control erosion on right-of-way construction sites, but disturbed conditions provide challenges. This research evaluated the impact of common techniques for preparing seedbeds. The study assessed the use of topsoil, and the use of a hydraulic erosion-control product was compared to straw. Experimental seed mixtures were evaluated to understand how native and non-native seeds performed. The intent was to identify critical practices to use in general seeding and mulching specifications. A plot study was conducted comparing vegetation established during one growing season. Treatments included combinations of seed mixture, topsoil treatment, and mulch types. Three seed mixtures were considered: (1) currently used mixture, (2) a warm-season experimental mixture, and (3) a cool-season experimental mixture. Plots with topsoil and no topsoil were compared, and both straw and hydraulic erosion control products were considered. Ground cover, compaction, and biomass were evaluated. Results suggest that alternative seed mixtures that include native and low-threat-level species can provide adequate cover to meet permitting requirements in the first growing season. The warm-season seed mixture provided less cover than the other two mixtures after eight days, but no differences were determined in ground cover among the three seed mixtures at the end of the growing season. Initial germination was improved with hydraulic mulch, but long-term cover was equivalent between hydraulic and straw mulch. Topsoil application would not be recommended if the soil contains undesirable species, and the use of organic amendment products may be more desirable than topsoil alone; however, specifications need to allow the use of these products.