Felodipine nanodispersions as active core for predictable pulsatile chronotherapeutics using PVP/HPMC blends as coating layer.
In the present study predictable pulsatile chronotherapeutics of felodipine (FELO), which is a poorly-water soluble drug, were prepared in the form of two layered tablets. As active core PVP/FELO nanodispersion was used while as effective coating layer different PVP/HPMC blends were added. From dissolution studies of FELO nanodispersions it was revealed that PVP/FELO 90/10 w/w dispersion is an ideal system for pulsatile formulations since the whole amount of FELO is released within the first 30 min. This dissolution enhancement and fast release was attributed to FELO amorphisation, as was found from XRD and DMTA techniques and the effective particle size reduction. Transmission electron microscopy (TEM) studies revealed that FELO creates amorphous nanodispersions into the PVP matrix while particle sizes are directly dependable upon FELO concentration. Drug particles with sizes lower than 150 nm may be the optimal level for a substantial enhancement of FELO dissolution rate. The time of FELO release initiated by the two-layered tablets was adequately adjusted by using different PVP/HPMC blends as coating layer, which is a swellable and erodible barrier. The delaying time of FELO release is directly depended by HPMC concentration and this correlation was mathematically expressed. The significance of these blends is that they are completely miscible over the entire compositional range, thus forming a new matrix with different physicochemical properties, contrary to the initial polymers.
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str. 6, Pallini Attikis, 153 51 Attiki, Greece.
Evangelos
E
Karavas
Emmanouel
E
Georgarakis
Dimitrios
D
Bikiaris
D002121:Calcium Channel Blockers / Q000737:chemistry*; D019454:Chronotherapy / Q000379:methods; D003692:Delayed-Action Preparations; D015736:Felodipine / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D036103:Nanotechnology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D011108:Polymers; D013608:Tablets, Enteric-Coated; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011205:Povidone; D015736:Felodipine