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Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO 2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO 2 assisted method, solid dispersions of CARV with the selected (co)polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus® and Eudragit®) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated δ p values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study consists of two experimental designs. Within the first one, suitable technique for application of model drug onto inactive pellets was evaluated and formulation and process parameters with greatest impact to process efficency and useful yield were determined. Results of experiments showed that formulation characteristics were the ones with the greatest impact on coating efficiency and that suspension layering technique was significantly better for drug application onto inactive pellets in comparison to solution layering during which pronounced agglomeration of pellets occurred. Analysis of drug-polymer interactions by differential scanning calorimetry was performed to explain the results of experiments. The reason for agglomeration of pellets during solution layering was formation of low Tg amorphous form of model drug. The second set of experiments was performed according to central composite design experimental plan in order to optimize level of binder and concentration of solids in the coating liquid which were found to have greatest positive impact on process efficiency and useful yield in the screening study. Statistically significant models were obtained by response surface methodology and it was possible to use them to define optimal levels of excipients in the formulation., (Copyright © 2016. Published by Elsevier B.V.)

The objective of this study was to develop artificial neural network (ANN) model suitable to predict successfully the borders of the microemulsion region in the quaternary system PEG-8 caprylic/capric glycerides (Labrasol)/cosurfactant/isopropyl myristate/water, in order to minimise experimental effort. In our preliminary investigations of phase behaviour, two cosurfactants were used, PEG-40 hydrogenated castor oil (Cremophor) RH 40) and polyglyceryl-6 isostearate (Plurol Isostearique). Microemulsion existance area in pseudo-ternary phase diagrams was determined using titration method at constant: (a) oil-to-water ratio (alpha=50%, w/w); (b) surfactant-to-cosurfactant ratio (Km) 4:6; (c) Km 5:5; or (d) Km 6:4. It was found that the phase behaviour of systems involving polyoxyethylene type of cosurfactant depends significantly on oil-to-surfactant/cosurfactant mixture mass ratio (O/SCoS) but it is Km-independent. The formation of microemulsions in Labrasol/polyglyceryl-6 isostearate based systems was a complex function of Km and O/SCoS and there was employed a Generalized Regression Neural Network (GRNN) with four layers as a predictive mathematical model, using data obtained from the phase behaviour study (the surfactant concentration in surfactant/cosurfactant mixture (S, %, w/w), the oil concentration in the mixture with tensides (O, %, w/w) as two input variables, and the water solubilization limit (W(max), %, w/w) as output data). After network training, six independent pairs of input/output data were used for network testing. The resulting GRNN was tested statistically and found to be of quality predictive power. This results confirmed that the trained GRNN could be effective in predicting the size of the microemulsion area providing valuable tool in formulation of this type of colloidal vehicles.