ABSTRACT
Introduction: Modafinil (MDF) is used orally for the treatment of attention-deficit/hyperactivity disorder and narcolepsy. It holds low solubility and high permeability; therefore, improving its dissolution properties by preparing nanoformulations can be a promising approach to enhance its oral absorption. Our aims were to prepare and characterize MDF-Eudragit® RS100 (MDF-ERS) nanoparticles by electrospray technique. Methods: Electrosprayed nanoparticles were fabricated by varying MDF to ERS ratios and concentrations. The formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). Release studies were performed on nanoparticles, physical mixtures, and raw MDF. The release data were fitted to different models to understand the mechanism of the drug release. Results: Electrospraying of MDF and ERS solution resulted in the preparation of nonobeads or nanofibers, and the particulate characteristics of the obtained products were largely controlled by the polymer amount in the solution. PXRD and thermal analyses showed that MDF was an amorphous phase in the structures of nanoparticles. Using FTIR, no interaction was observed between MDF and ERS in nanoparticles. Nanoparticles showed biphasic release profiles and the order of dissolution rates was: nanofibers>MDF>nanobeads. The well-fitted model was Weibull model, indicating a Fickian diffusion as the main mechanism of release. Conclusion: The results suggest that by optimization of variables such as solution concentration of MDF-ERS nanofibers and nanobeads with higher dissolution rates can be made by electrospray. Electrospray deposition as a simple, continuous, and surfactant free method is an excellent choice for preparation of drug loaded polymeric nanoparticles.
ABSTRACT
OBJECTIVES: This study was carried out to boost the pharmacologic influence of carvedilol (CAR) (as a poorly water-soluble drug) by developing CAR-eudragit® RS100 (Eud) nanofibers and nanobeads benefiting an electrospraying approach. MATERIALS AND METHODS: CAR-Eud nanoformulations with varying ratios (1:5 and 1:10) at total solution concentrations of 10 %, 15 % and 20 % w/v were formulated. RESULTS: The solution concentration remarkably impressed the size and morphology of the samples; in which, the nanobeads (mean diameter of 135.83 nm) were formed at low solution concentrations and high concentrations led to nanofibers (mean diameter of 193.45 nm) formation. DSC thermographs and PXRD patterns along with FTIR spectrum precisely showed CAR amorphization and no probable chemical interactions between CAR and Eud in the electrosprayed nanosystems. The in vitro release considerations demonstrated that the nanoformulations with the drug: polymer ratios of 1:10 and 1:5 depict rapid dissolution rate compared to the physical mixtures (PMs) and the pure drug. The in vivo studies in Wistar male rats suggested that the electrosprayed nanoformulation (1:10; 20 %) reduced the isoproterenol (ISO) induced elevation of heart rate, necrosis and accumulation of neutrophils in the heart tissue more efficient than the pure drug and PM. CONCLUSION: Our finding illustrated that the electrospraying as a profitable one-step procedure could be productively benefited to improve the physicochemical features and pharmacologic influences of CAR.
ABSTRACT
This study was conducted to enhance the pharmacologic effect of carbamazepine (CBZ) (as a poorly water-soluble drug) by fabricating CBZ-PVP K30 nanobeads using an electrospraying technique. CBZ-PVP K30 nanosystems with various ratios (1:3 and 1:5) at total solution concentrations of 3% and 5% w/v were prepared. The solution concentration extremely affected the size of the samples; where, the nanobeads (mean diameter of 457.65 ± 113.72 nm and 1.16 ± 0.46 µm) were developed at low and high solution concentrations, respectively. DSC thermographs and PXRD patterns precisely showed CBZ amorphization in the electrosprayed nanosystems. Based on the FTIR spectrum of the electrosprayed samples, a feasible interaction between N-H/O-H group of CBZ and PVP carbonyl group was detected. The in-vitro release studies revealed that the electrosprayed nanosystems represent a comparable rapid dissolution rate with respect to the physical mixtures (PMs) and the pure drug. The in-vivo results in NMRI mice indicated that the electrosprayed nanoformulation (with the drug: polymer ratio of 1:5 at a total solution concentration of 5% (w/v)) prolonged seizure latency time and decreased mortality percent in strychnine (STR) induced seizure mice more efficiently than the PM. Our finding revealed that the electrospraying as a cost-benefit and one step technique could be effectively applied for improving the physicochemical characteristics and pharmacologic effect of CBZ.
