Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO₂, and their nanocomposites as appropriate drug carriers

Abstract

Background: Creation of immediate release formulations for the poorly water-soluble drug Tibolone through the use of solid dispersions (SDs). Aim: SD systems of Tibolone (Tibo) with poly(vinylpyrrolidone) (PVP), fumed SiO₂ nanoparticles, and their corresponding ternary systems (PVP/SiO₂/Tibo) were prepared and studied in order to produce formulations with enhanced drug dissolution rates. Method: 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 SiO₂ 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/SiO₂/Tibo SDs. The dissolution profiles of the drug in PVP/Tibo and SiO₂/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/SiO₂/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 SiO₂, which result in alterations of the characteristics of the carrier (PVP/SiO₂ nanocomposites). Conclusions: Immediate release formulation was created for Tibolone as well as new nanocomposite matrices of PVP/SiO₂, which drastically change the release profile of the drug to a sustained delivery.

Keywords:

• Dissolution rate enhancement
• PVP
• silica nanoparticles
• solid dispersion
• Tibolone

Acknowledgments

This work was funded by the Greek Ministry of Development under the 3rd European Community Support Framework, Operational Program ‘Competiveness’ 2000–2006 (PENED, 78108).

Declaration of interest: The authors report no conflicts of interest.