Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO2, and their nanocomposites as appropriate drug carriers.
BACKGROUND
Creation of immediate release formulations for the poorly water-soluble drug Tibolone through the use of solid dispersions (SDs).


OBJECTIVE
SD systems of Tibolone (Tibo) with poly(vinylpyrrolidone) (PVP), fumed SiO(2) nanoparticles, and their corresponding ternary systems (PVP/SiO(2)/Tibo) were prepared and studied in order to produce formulations with enhanced drug dissolution rates.


METHODS
The prepared SDs were characterized by the use of differential scanning calorimetry and wide-angle X-ray diffractometry techniques. Also dissolution experiments were performed.


RESULTS
From the results it was concluded that PVP as well as SiO(2) can be used as appropriate carriers for the amorphization of Tibo, even when the drug is used at high concentrations (20-30%, w/w). This is due to the evolved interactions taking place between the drug and the used carriers, as was verified by Fourier transform infrared spectroscopy. At higher concentrations the drug was recrystallized. Similar are the observations on the ternary PVP/SiO(2)/Tibo SDs. The dissolution profiles of the drug in PVP/Tibo and SiO(2)/Tibo SDs are directly dependent on the physical state of the drug. Immediately release rates are observed in SD with low drug concentrations, in which Tibo was in amorphous state. However, these release profiles are drastically changed in the ternary PVP/SiO(2)/Tibo SDs. An immediate release profile is observed for low drug concentrations and an almost sustained release as the concentration of Tibo increases. This is due to the weak interactions that take place between PVP and SiO(2), which result in alterations of the characteristics of the carrier (PVP/SiO(2) nanocomposites).


CONCLUSIONS
Immediate release formulation was created for Tibolone as well as new nanocomposite matrices of PVP/SiO((2)), which drastically change the release profile of the drug to a sustained delivery.
Papadimitriou
Sofia
S
Department of Chemistry, Laboratory of Organic Chemical Technology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Bikiaris
Dimitrios
D
D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D009652:Norpregnenes / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D010592:Pharmaceutic Aids; D011205:Povidone; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D004337:Drug Carriers; D009652:Norpregnenes; D010592:Pharmaceutic Aids; D020845:Selective Estrogen Receptor Modulators; D012822:Silicon Dioxide; C027385:tibolone; D011205:Povidone