Development of ß-cyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) hybrid nanogels as nano-drug delivery carriers to enhance the solubility of Rosuvastatin: An in vitro and in vivo evaluation.

The present study is aimed at enhancing the solubility of rosuvastatin (RST) by designing betacyclodextrin/polyvinypyrrolidone-co-poly (2-acrylamide-2-methylpropane sulphonic acid) crosslinked hydrophilic nanogels in the presence of crosslinker methylene bisacrylamide through free-radical polymerization method. Various formulations were fabricated by blending different amounts of betacyclodextrin, polyvinylpyrrolidone, 2-acrylamide-2-methylpropane sulphonic acid, and methylene bisacrylamide. The developed chemically crosslinked nanogels were characterized by FTIR, SEM, PXRD, TGA, DSC, sol-gel analysis, zeta size, micromeritics properties, drug loading percentage, swelling, solubility, and release studies. The FTIR spectrum depicts the leading peaks of resultant functional groups of blended constituents while a fluffy and porous structure was observed through SEM images. Remarkable reduction in crystallinity of RST in developed nanogels revealed by PXRD. TGA and DSC demonstrate the good thermal stability of nanogels. The size analysis depicts the particle size of the developed nanogels in the range of 178.5 ±3.14 nm. Drug loading percentage, swelling, solubility, and release studies revealed high drug loading, solubilization, swelling, and drug release patterns at 6.8 pH paralleled to 1.2 pH. In vivo experiments on developed nanogels in comparison to marketed brands were examined and better results regarding pharmacokinetic parameters were observed. The compatibility and non-toxicity of fabricated nanogels to biological systems was supported by a toxicity study that was conducted on rabbits. Efficient fabrication, excellent physicochemical properties, improved dissolution, high solubilization, and nontoxic nanogels might be a capable approach for the oral administration of poorly water-soluble drugs.

Engineering of Long-Term Stable Transparent Nanoemulsion Using High-Gravity Rotating Packed Bed for Oral Drug Delivery.

BACKGROUND: Oil-in-water drug nanoemulsion forms drug delivery systems with high oral bioavailability. The conventional fabrication methods of nanoemulsion are low energy emulsification methods and high energy emulsification methods. However, both two methods are not ideal for industrial production. The problem of low energy emulsification methods is the high dosage of surfactant and co-surfactant which has potential biosecurity issues. What is more, high energy emulsification methods have some disadvantages, like the destruction of drug components, the price of equipment and the difficulties of industrial production. Hence, there have been a few commercial drug nanoemulsions so far. METHODS: In this work, we reported a novel method for the fabrication of stable and transparent drug nanoemulsion which contains hydrophilic drug rosuvastatin (ROS) calcium or hydrophobic drug silybinin (SYN) by using high-gravity rotating packed bed (RPB). The drug nanoemulsion was systematically characterized by droplet size, size distribution, stability and in vitro drug release as well as Caco-2 cells permeability. RESULTS: Compared with the self-emulsification method (SE), high-gravity technology could reduce 75% amount of mixed surfactants. The as-prepared nanoemulsion exhibited a very narrow droplet size distribution with a size of 13.53 ± 0.53 nm and a polydispersity index of 0.073 ± 0.018. Meanwhile, the drug nanoemulsion was physicochemically stable at 25°C and 4°C for one-year storage. Furthermore, both ROS and SYN nanoemulsion displayed higher cell permeability and in vitro dissolution than that of commercial formulations. CONCLUSION: These results demonstrate that RPB can be a potential device to facilitate the industrial production of drug nanoemulsion.

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation.

The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.0 ± 3.0 and 60.0 ± 5.0 mg/mL, respectively. Later, nanophasic maps and a central composite design were employed to determine the maximum nanoemulsion region and further optimize SNES in this study. Finally, the optimized formulation was evaluated in vitro and in vivo. FAME analysis revealed that PUFA content was 70.3% of total fatty acid. Optimized SNES formulation demonstrated particle size of 17.90 nm, dissolution 98.80%, cloud point 45°C, emulsification time 2 min, and viscosity 241.41 ± 5.52 cP. The hypolipidemic property of SNES was further explored using Triton X-100-induced hyperlipidemic rat model, and there were reductions of serum cholesterol, triglyceride, and LDL and VLDL levels in the SNES-treated group as compared to the toxic control. Pharmacokinetic study of SNES revealed significantly higher C max (60.13 ± 25.43 ng/mL) and AUC0-∞ (6195 ± 42.38 ng h/mL) vis-à-vis marketed tablet (284.80 ± 13.44 ng/mL, 3131.72 ± 51.93 ng h/mL, respectively). RSV was successfully incorporated into ω-3 fatty acid-based SNES with improved pharmacokinetic parameters (~ 2-fold improved bioavailability) and better hypolipidemic properties, owing to the synergistic effects of hepatic lipid regulation itself. The results clearly explicated that ω-3 fatty acid-based SNES effectively enhanced bioavailability and pharmacological responses of RSV, suggesting that these formulations may be useful as alternative for hyperlipidemia treatment in future drug design perspective.