Preparation and evaluation of raloxifene-loaded solid dispersion nanoparticle by spray-drying technique without an organic solvent

• Published in: International journal of pharmaceutics 2013-02, Vol.443 (1-2), p.50-57
• Main Authors: Tran, Tuan Hiep, Poudel, Bijay K., Marasini, Nirmal, Chi, Sang-Cheol, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Calorimetry, Differential Scanning; differential scanning calorimetry; Drug Carriers - chemistry; Drug Compounding - instrumentation; Drug Compounding - methods; drugs; Excipients - chemistry; Male; Molecular Structure; Nanoparticles; Nanoparticles - chemistry; Particle Size; pharmacokinetics; Phase Transition; polysorbates; Polysorbates - chemistry; Povidone - chemistry; Raloxifene; Raloxifene Hydrochloride - administration & dosage; Raloxifene Hydrochloride - blood; Raloxifene Hydrochloride - chemistry; Raloxifene Hydrochloride - pharmacokinetics; Rats; Rats, Sprague-Dawley; Selective Estrogen Receptor Modulators - administration & dosage; Selective Estrogen Receptor Modulators - blood; Selective Estrogen Receptor Modulators - chemistry; Selective Estrogen Receptor Modulators - pharmacokinetics; Solubility; solvents; Solvents - chemistry; Spray drying; Surface Properties; Water - chemistry; X-Ray Diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.01.013

The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble drug, raloxifene by solid dispersion (SD) nanoparticles using the spray-drying technique. These spray-dried SD nanoparticles were prepared with raloxifene (RXF), polyvinylpyrrolidone (PVP) and Tween 20 in water. Reconstitution of optimized RXF-loaded SD nanoparticles in pH 1.2 medium showed a mean particle size of approximately 180nm. X-ray diffraction and differential scanning calorimetry indicated that RXF existed in an amorphous form within spray-dried nanoparticles. The optimized formulation showed an enhanced dissolution rate of RXF at pH 1.2, 4.0, 6.8 and distilled water as compared to pure RXF powder. The improved dissolution of raloxifene from spray-dried SD nanoparticles appeared to be well correlated with enhanced oral bioavailability of raloxifene in rats. Furthermore, the pharmacokinetic parameters of the spray-dried SD nanoparticles showed increased AUC0–∞ and Cmax of RXF by approximately 3.3-fold and 2.3-fold, respectively. These results suggest that the preparation of RXF-SD nanoparticles using the spray drying technique without organic solvents might be a promising approach for improving the oral bioavailability of RXF.