Improvement in chemical and physical stability of fluvastatin drug through hydrogen bonding interactions with different polymer matrices.
Solid dispersions of Fluvastatin with polyvinylpyrrolidone (PVP), eudragit RS100 (Eud), and chitosan (CS) as drug carrier matrices, were prepared using different techniques in order to evaluate their effect on Fluvastatin stability during storage. The characterization of the three different systems was performed with the use of differential scanning calorimetry (DSC) and wide angle X-ray diffractometry (WAXD). It was revealed that amorphization of the drug occurred in all of the solid dispersions of Fluvastatin as a result of drug dissolution into polymer matrices and due to physical interactions (hydrogen bonding) between the polymer matrix and Fluvastatin. This was established through the use of FTIR spectroscopy. SEM and micro-Raman spectroscopy showed that Fluvastatin was interspersed to the polymer matrices in the form of molecular dispersion and nanodispersion, too. The finding that completely different polymer matrices, used here as drug carriers, produce completely different dissolution profiles for each one of the solid dispersions, suggests that each matrix follows a different drug release mechanism. Hydrogen bonding interactions as in the case of CS/Fluva solid dispersions lead to controlled release profiles. All formulations were subjected to accelerated aging in order to evaluate Fluvastatin stability. From by-products analysis it was found that Fluvastatin is very unstable during storage and anti-isomer as well as lactones are the main formed by-products. On the other hand, solid dispersions due to the evolved interactions of their reactive groups with Fluvastatin provide a sufficient physical and chemical stability. The extent of interactions seems to play the most important role in the drug stabilization.
Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
G Z
GZ
Papageorgiou
S
S
Papadimitriou
E
E
Karavas
E
E
Georgarakis
A
A
Docoslis
D
D
Bikiaris
D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry; D004355:Drug Stability; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D000077340:Fluvastatin; D006860:Hydrogen Bonding; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D014961:X-Ray Diffraction
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011108:Polymers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D000077340:Fluvastatin; D048271:Chitosan; D011205:Povidone