Weibull mixture model Dotaz Zobrazit nápovědu
Salidroside, as a chemical compound from the group of phenylpropanoids, and rosavin are used for the standardization of dry extracts from the underground stem and root of Rhodiola rosea. In this study we monitored two different extracts from Rhodiola rosea, which differ in content of active compounds, colour, technological and physico-chemical properties (e.g. flow properties). These extracts were mixed with excipients and the flow characteristics of mixture – bulk volume and tapped volume – were determined. After formulating the tablets by compression, qualitative parameters like disintegration, resistance to crushing, friability, mass uniformity and texturometric parameters were tested. Also, dissolution profiles were evaluated using first order kinetic model, Korsmeyer-Peppas model and Weibull model for correlation. In some formulations, the impact of the properties of dry extracts on various technological properties of final tablets was more marked. We suggest that in case of a higher extract:excipients ratio, these properties manifest themselves by an even higher impact.
Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5-25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion-surface utilization factor-were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing.
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