Optimization and Evaluation of Self-nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Plumbagin.

Plumbagin, a potential bioactive lipophilic molecule, possesses limited solubility and low oral bioavailability. The purpose of the present study was to examine the potential of the self-nanoemulsifying drug delivery system for improving solubility and oral bioavailability of plumbagin. The self-nanoemulsifying drug delivery system was formulated from Capmul MCM (oil), Tween 20 (surfactant), and propylene glycol (cosurfactant). Central composite design was employed as statistical tool to optimize the formulation variables, X1 (oil) and X2 (surfactant: co-surfactant mixture ratio), of the self-nanoemulsifying drug delivery system. The responses studied were droplet size, self-emulsification time, % of drug release in 15 min, and equilibrium solubility. The optimized liquid self-nanoemulsifying drug delivery system was adsorbed on Neusilin US2 and characterized for flow properties, X-ray diffractometry, differential scanning calorimetry, in vitro dissolution, in vivo anti-inflammatory activity, and bioavailability study in Wistar rats, as well as ex vivo permeation study. The droplet size, polydispersity index, self-emulsification time, and equilibrium solubility of the optimized formulation were 58.500 ± 1.170 nm, 0.228 ± 0.012, 17.660 ± 1.520 s, and 34.180 ± 1.380 mg/mL, respectively. Its zeta potential, transmittance value, and cloud point were - 28.200 ± 1.200 mV, 99.200% ± 0.600, and 90 °C, respectively. Drug release was found to be 93.320% ± 1.090. In vivo anti-inflammatory study confirmed more enhanced activity from the self-nanoemulsifying drug delivery system than with pure plumbagin. Pharmacokinetic study in rats revealed that solid self-nanoemulsifying drug delivery system had 4.49-fold higher bioavailability than pure plumbagin. Ex vivo permeation study demonstrated 1.75-fold increased intestinal permeability of the self-nanoemulsifying drug delivery system than pure plumbagin. The developed self-nanoemulsifying drug delivery system is a useful solid platform for improving solubility and oral bioavailability of plumbagin.

Application of liquisolid technology for enhancing solubility and dissolution of rosuvastatin.

PURPOSE: Rosuvastatin is a poorly water soluble drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Hence it is necessary to increase the solubility of the Rosuvastatin. METHODS: Several liquisolid tablets formulations containing various drug concentrations in liquid medication (ranging from 15% to 25% w/w) were prepared. The ratio of Avicel PH 102 (carrier) to Aerosil 200 (coating powder material) was kept 10, 20, 30. The prepared liquisolid systems were evaluated for their flow properties and possible drug-excipient interactions by Infrared spectra (IR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD). RESULTS: The liquisolid system showed acceptable flow properties. The IR and DSC studies demonstrated that there is no significant interaction between the drug and excipients. The XRPD analysis confirmed formation of a solid solution inside the compact matrix. The tabletting properties of the liquisolid compacts were within the acceptable limits. Liquisolid compacts demonstrated significantly higher drug release rates than those of conventional and marketed tablet due to increasing wetting properties and surface area of the drug. CONCLUSION: This study shows that liquisolid technique is a promising alternative for improvement of the dissolution rate of water insoluble drug.