Optimizing the ability of PVP/PEG mixtures to be used as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique using artificial neural networks: I.

In the present study, the efficiency of PVP/PEG200 mixtures as appropriate carries for the preparation of solid dispersions by melt mixing was evaluated. Felodipine (FELO) was used as a poorly water soluble model drug. The effect of several melt mixing parameters, (PVP/PEG ratio, time and temperature of melt mixing, and drug content), on the physical state of FELO and the dissolution characteristics of the dispersions were investigated. DSC, XRD, and SEM analysis revealed that in all cases, amorphous drug nanodispersions were prepared. This was attributed to the increased miscibility of the PVP-FELO system, induced by the presence of PEG200, which acted as plasticizer. FT-IR analysis showed hydrogen bonding between FELO (NH) and the PVP carrier (CO). The release rate of the drug depends mainly on the drug content and is higher in solid dispersions with low drug content and ratio of carrier to plasticizer (PVP/PEG200). The melt mixing variations (time and temperature of mixing) had lower impact on FELO release rate. Finally, artificial neural networks, used to correlate the examined formulation and process variables of hot melt mixing with dissolution parameters, showed good prediction ability.

Papadimitriou SA ，Barmpalexis P ，Karavas E ，Bikiaris DN ... -  《-》

Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks.

The effect of plasticizer's (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000 g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous. Furthermore, a single Tg recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG's molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices. All prepared solid dispersion showed long-term physical stability (18 months in room temperature). The extent of interaction between mixture components was verified using Fox and Gordon-Taylor equations. Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability.

Barmpalexis P ，Koutsidis I ，Karavas E ，Louka D ，Papadimitriou SA ，Bikiaris DN ... -  《-》

Investigation of the release mechanism of a sparingly water-soluble drug from solid dispersions in hydrophilic carriers based on physical state of drug, particle size distribution and drug-polymer interactions.

Karavas E ，Georgarakis E ，Sigalas MP ，Avgoustakis K ，Bikiaris D ... -  《EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》

A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine.

To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks. Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations.

Mahmah O ，Tabbakh R ，Kelly A ，Paradkar A ... -  《-》

Physicochemical characterization of artemether solid dispersions with hydrophilic carriers by freeze dried and melt methods.

Ansari MT ，Karim S ，Ranjha NM ，Shah NH ，Muhammad S ... -  《-》