Abstract
Objective: The poor water solubility of the drug presents a great challenge for the formulation development and results in low oral bioavailability. The oral bioavailability of Raloxifene HCl (RLX) is very low (<2%) in humans due to its poor solubility. The objective of the present study was to develop RLX loaded solid-liquid nanoparticles for effective drug delivery.
 Methods: Compritol 888 ATO-based RLX-loaded solid lipid nanoparticles (SLNs) were formulated using the oil in water microemulsion method. Drug-excipients compatibility was confirmed through Fourier transform infrared spectroscopy, Differential scanning calorimetry methods. The SLN was characterized for particle size, surface morphology, entrapment efficiency.
 Results: A total of seventeen formulations (SLN1-SLN17) were developed as per the 3 levels 3 factor Box–Behnken design. The model used for the analysis was statistically analyzed using ANOVA and the goodness of fit was evaluated using diagnostic plots. As per the response-surface plots, the amount of lipid, poloxamer 407, and ultrasonication time have a significant effect on the particle size and entrapment efficiency (%EE). The developed RLX-loaded SLNs have the size and %EE in the range of 165.63±2.62 nm to 315.33±4.87 nm and 75.21±2.32% to 95.32±2.11%. The TEM analysis showed that the developed RLX-loaded SLNs were almost spherical and has a small size range.
 Conclusion: The high biocompatibility, biodegradability, ability to protect drugs in GIT, and sustained release properties make SLNs an ideal candidate to resolve poor oral bioavailability challenges.
Highlights
Raloxifene hydrochloride (RLX) is a second-generation selective estrogen receptor modulator (SERM) that has anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation [1] It is considered first-line therapy for the management of postmenopausal osteoporosis [2]
We have investigated the drugexcipients compatibility by Fourier transform infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC) The model used for the optimization was analyzed statistically via analysis of variance (ANOVA), and the goodness of fit was evaluated through different diagnostic plots
The FTIR spectrum of RLX showed characteristic peaks at 3465.27 cm-1 (O-H stretching), 2938.42 cm-1 (Aromatic C-H bond), 1603.88 cm-1 (C=O stretching), 1500.68 cm-1 (Aromatic C=C), 1463.07 cm-1 (–S–benzothiophene), 1263.43 cm-1 and 1039.68 cm-1 (fig. 1(A)). These characteristic peaks are visible in the physical mixture of RLX and Compritol 888 ATO, and RLX and poloxamer 407 (P407) (fig. 1 (B and C)
Summary
Raloxifene hydrochloride (RLX) is a second-generation selective estrogen receptor modulator (SERM) that has anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation [1] It is considered first-line therapy for the management of postmenopausal osteoporosis [2]. Poor solubility of the RLX (0.25 mg/lit) results in only 60% absorption of the administered dose and poor oral bioavailability (less than 2%). Extensive first-pass metabolism of RLX by glucuronide conjugation results in poor oral bioavailability [3]. The poor water solubility and poor oral bioavailability present a continuous challenge for the formulation development and effective treatment of the diseases. There is an unmet need for an effective delivery system that can overcome the existing challenges
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