Combining SEM, TEM, and micro-Raman techniques to differentiate between the amorphous molecular level dispersions and nanodispersions of a poorly water-soluble drug within a polymer matrix.
The aim of the present study was to experimentally examine whether poorly water-soluble drugs dispersed in a polymeric matrix exist as amorphous nanodispersions or molecularly dispersed compounds. Felodipine (Felo) dispersed in PVP matrix (solid dispersion) was used as a model drug in this study. Drug/polymer ratios have an impact on the drug average particle size, morphology and dissolution profile while solid dispersions containing up to 50wt% Felo are completely amorphous. SEM, TEM micrographs, and micro-Raman mapping reveal that Felo is dispersed in the form of nanoparticles into the PVP matrix. Due to the high spatial resolution of TEM, it was established that these nanoparticles are not uniform particles, but rather agglomerates of individual particles with sizes smaller than 5-10nm. Moreover, micro-Raman mapping allowed us to observe the size and spatial distribution of domains where the drug existed as molecularly or nanodispersed. Experimental evidence presented in this work contradicts the common belief that amorphous poorly water-soluble drugs exist only in the state of molecular dispersion inside a polymer matrix by showing that both types of dispersions (molecular-level and nanodispersions) can coexist.
Karavas
Evangelos
E
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str. 6, Pallini Attikis, 153 51 Attiki, Greece.
Georgarakis
Manolis
M
Docoslis
Aristides
A
Bikiaris
Dimitrios
D
D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D015736:Felodipine / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry*
D004337:Drug Carriers; D014867:Water; D011205:Povidone; D015736:Felodipine