Preformulation and characterization of raloxifene-loaded lipid nanoparticles for transdermal administration.

Abstract

Transdermal administration of raloxifene hydrochloride (RLX)-loaded nanostructured lipid carriers (NLCs) has been proposed to circumvent its low oral bioavailability (2%). Preformulation studies were carried out to evaluate drug-excipient compatibility of various adjuvants commonly used for NLC preparation (waxes, cholesterol, compritol, gelucire, span 60, span 80, span 85, tween 80, poloxamer 188, oleic acid, caprylic/capric triglyceride, and castor oil). It was used differential scanning calorimetry (DSC), isothermal stress testing (IST), and solubility studies. The most promising excipients were chosen for NLC obtention, and full characterization was done, including in vitro skin permeation. DSC curves suggested drug-excipient interaction among some compounds, and the IST study showed incompatibility of RLX with waxes, compritol, cholesterol, span 60, and poloxamer 188. Solubility studies helped select gelucire, caprylic/capric triglyceride, span 80, and tween 80 for NLC production. Twelve NLCs were obtained (NLC1 to NLC12), but NLC7 and NLC8 were the most promising ones. In vitro release studies demonstrated that NLC7 and NLC8 were able to control RLX release (14.74 and 9.07% at 24h, respectively) compared with the unloaded drug (> 90% at 24h). Unloaded RLX did not permeate the diffusion cells' receptor medium and showed higher drug skin retention (11-fold) than RLX-loaded NLC. NLC reduced RLX skin retention, favoring drug permeation to deeper skin layers. NLC7 increased drug flux is 2.4-fold. NLC7 is a promising formulation for RLX transdermal drug delivery.