Drug Development and Industrial Pharmacy, 2009; 35(9): 1128–1138 ISSN 0363-9045 print/ISSN 1520-5762 online © Informa UK, Ltd. DOI: 10.1080/03639040902787653 http://www.informapharmascience.com/ddi LDDI ORIGINAL RESEARCH PAPER Dissolution rate enhancement of the poorly water-soluble drug Tibolone using PVP, SiO 2 , and their nanocomposites as appropriate drug carriers Tibolone solid dispersions Sofia Papadimitriou and Dimitrios Bikiaris Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece 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 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. Method: The prepared SDs were characterized by the use of differential scanning calorimetry and wide-angle X-ray diffractome- try 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 nano- composites). Conclusions: Immediate release formulation was created for Tibolone as well as new nano- composite matrices of PVP/SiO 2 , which drastically change the release profile of the drug to a sustained delivery. Key words: Dissolution rate enhancement; PVP; silica nanoparticles; solid dispersion; Tibolone Introduction Solid dispersion (SD) seems to be one of the most successfully used method for the improvement of the dissolution properties of poorly water-soluble drugs minimizing the limitations of oral bioavailability 1–5 . According to the Noyes–Whitney equation, the most attractive and easy way to enhance the release rate of the drug is to increase its surface area by reducing the parti- cle size rather than to increase drug solubility 6–8 . Addi- tionally, factors that can contribute to this direction are to optimize the wetting characteristics of the compound surface, decreasing the boundary layer thickness, ensuring appropriate conditions for dissolution and improving the apparent solubility of the drug under physiologically relevant conditions 9 . Water-soluble poly- mers are widely and repeatedly used as carriers of solid dispersions, from which drugs are released quickly 10 . Poly(vinylpyrrolidone) (PVP) is a readily water-soluble macromolecular compound, as well as in most com- mon polar organic solvents, such as alcohols, amines, acids, and chlorinated hydrocarbons, exhibiting excep- tional low toxicity and high biocompatibility. It is found in the form of a white powder, with many applications Address for correspondence: Professor Dimitrios Bikiaris, Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece. Tel: +30 2310 997812, fax: +30 2310 997769. E-mail: dbic@chem.auth.gr (Received 2 Jun 2008; accepted 30 Jan 2009) Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by University of Sydney on 08/27/14 For personal use only.