Effectiveness of various drug carriers in controlled release formulations of raloxifene HCl prepared by melt mixing.
In the present study solid dispersions of Raloxifene HCl were prepared by melt mixing. As drug carriers, biodegradable/biocompatible aliphatic polyesters were used. These formulations were compared to those based on extensively used drug carriers such as PEG and Gelucire 50/13. The used aliphatic polyesters namely poly(propylene succinate) (PPSu) and poly(propylene adipate) (PPAd) were prepared by melt polycondensation. The polyesters have melting points close to human body temperature and were used for first time as drug carries. Polymer cytocompatibility based on HUVEC cells viability in the presence of increasing concentrations of polymer was investigated and it was found that PPSu and PPAd exhibit comparable cytocompatibility with poly(dl-lactide). The physical state of solid dispersions was evaluated by FTIR, SEM and XRD techniques. In all cases the interactions between drug and carriers are limited and thus the dispersed drug was mainly in the crystalline state. SEM revealed that the particles size of the dispersed drug increases with increasing the drug amount. The release behavior of the drug is affected from both the drug amount and the kind of the used carrier. The drug is released almost immediately from PEG formulations while Gelucire results in sustained release. In formulations that polyesters were used as drug carriers the release is slower.
Bikiaris
Dimitrios
D
Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece. dbic@chem.auth.gr
Karavelidis
Vassilios
V
Karavas
Evangelos
E
D000272:Adipates / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000138:chemical synthesis; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D004355:Drug Stability; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D011095:Polyethylenes / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D011126:Polypropylenes / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D020849:Raloxifene Hydrochloride / Q000737:chemistry*; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013386:Succinates / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D044366:Transition Temperature; D014961:X-Ray Diffraction
D000272:Adipates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011095:Polyethylenes; D011126:Polypropylenes; D020845:Selective Estrogen Receptor Modulators; D013386:Succinates; C443715:poly(ethylene succinate); C541439:poly(propylene succinate); C084250:poly(propylene adipate); D020849:Raloxifene Hydrochloride