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.
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Sofia A
SA
Papadimitriou
Panagiotis
P
Barmpalexis
Evangelos
E
Karavas
Dimitrios N
DN
Bikiaris
D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D015736:Felodipine / Q000008:administration & dosage* / Q000737:chemistry; D006860:Hydrogen Bonding; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D016571:Neural Networks, Computer; D010968:Plasticizers / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction
D004337:Drug Carriers; D010968:Plasticizers; D011092:Polyethylene Glycols; D011205:Povidone; D015736:Felodipine