Novel surface modified polymer–lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation

Here we report fabrication and evaluation of novel surface modified polymer–lipid hybrid nanoparticles (PLN) as robust carriers for intranasal delivery of ropinirole hydrochloride (ROPI HCl). Sustained release, avoidance of hepatic first pass metabolism, and improved therapeutic efficacy are the major objectives of this experiment. PLN were fabricated by emulsification-solvent diffusion technique and evaluated for physicochemical parameters, in vitro mucoadhesion, in vitro diffusion, ex vivo permeation, mucosal toxicity and stability studies. Box-Behnken experimental design approach has been employed to assess the influence of two independent variables, viz. surfactant (Pluronic F-68) and charge modifier (stearylamine) concentration on particle size, ζ-potential and entrapment efficiency of prepared PLN. Numerical optimization techniques were used for selecting optimized formulation sample, further confirmed by three dimensional response surface plots and regression equations. Results of ANOVA demonstrated the significance of suggested models. DSC and SEM analysis revealed the encapsulation of amorphous form of drug into PLN system, and spherical shape. PLN formulation had shown good retention with no severe signs of damage on integrity of nasal mucosa. Release pattern of drug-loaded sample was best fitted to zero order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were executed to compare therapeutic efficacy of prepared nasal PLN formulation against marketed oral formulation of same drug. In summary, the PLN could be potentially used as safe and stable carrier for intranasal delivery of ROPI HCl, especially in treatment of Parkinson’s disease.     

Development of pellets of nifedipine using HPMC K15 M and κ-carrageenan as mucoadhesive sustained delivery system and in vitro evaluation

Polymeric mucoadhesive pellets of nifedipine were designed using computer software and they were prepared by extrusion-spheronization using HPMC K15M and κ-carrageenan with microcrystalline cellulose. A randomized rotatable two factor central composite design was applied for assessment of influence of two independent variables such as concentration of κ-carrageenan and HPMC K15M on dependent variables. Pellets were characterized by FTIR, DSC, SEM, flow properties, particle size, abrasion resistance, sphericity, drug content, percent production yield, in vitro drug release, ex vivo mucoadhesion, stability studies and similarity factor. The optimized formulation was selected based on criteria of sphericity nearest to 1.0 with maximum cumulative drug release percentage. Formulation NF6 exhibited sufficient porous spheres, free flowing and smooth surface mucoadhesion of 91.34 % and drug content 98.22 ± 0.37 %. Kinetic modeling revealed that the formulation followed the Higuchi model and showed the Quassi-Fickian drug release mechanism. The similarity factor, F2 value, was found to be 74 ± 6 and there was no significant change in drug content and ex vivo mucoadhesion after 90 days at 40 ± 2 °C, and 75 ± 5 % RH clearly indicated the optimized batch NF6 was stable. Thus, it can be concluded that use of κ-carrageenan, microcrystalline cellulose and HPMC K15M at the 20:35:10 w/w ratio could provide an effective carrier for enhancement of sphericity and sustained release of matrix pellets.     

Effect of Graphene Nanoplatelets Addition on the Mechanical,Tribological and Corrosion Properties of Cu–Ni/Gr Nanocomposite Coatings by Electro-co-deposition Method

Transactions of the Indian Institute of Metals - Nowadays, corrosion of metals is a major problem faced by marine, chemical and automobile industries. Therefore, several researchers are taking...     

Fault diagnosis of rolling element bearing based on artificial neural network

Journal of Mechanical Science and Technology - This paper proposes the expert system for accurate fault detection of bearing. The study is based upon advanced signal processing method as wavelet...     

Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization and evaluation

The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2(3) factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320-498?nm, and the EE was between 32.89 and 56.56?%. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery.     

Self-Assembled,Chitosan Grafted PLGA Nanoparticles for Intranasal Delivery: Design,Development and Ex Vivo Characterization

The objective of present study was to modify the surface of Poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) with chitosan to enhance the mucoadhesive potential of carrier system. Grafting of chitosan on PLGA surface was carried out via amide bond formation mediated by carbodiimide and confirmed by FTIR spectroscopy. Self-assembled PLGA NPs containing chlorpromazine hydrochloride were fabricated by 2³ factorial design. The improved mucoadhesive potential was confirmed by several tests including in vitro mucoadhesion study. Ex vivo permeation was satisfactory. Histopathological study on sheep nasal mucosa revealed safe mucoadhesion. They were also found to be robust on accelerated stability study.     

Influence of novel carrier Soluplus® on aqueous stability,oral bioavailability,and anticancer activity of Morin hydrate

Present work demonstrated the influence of novel amphiphilic carrier Soluplus^® on the solubility and oral bioavailability of Morin hydrate (MOR). Spray-dried solid dispersions (SSD) were developed using the design of experiment (DoE). Saturation solubility study of the optimized formulation SSD F(7) showed many fold increment in the solubility with acceptable aqueous stability. In vitro drug diffusion kinetics suggested Weibull model to be the best fit. In vitro cytotoxicity assay revealed a significant increase in the anticancer potential compared to innate MOR. Furthermore, SSD F(7) showed 2.27-fold enhancement in the relative bioavailability as compared to MOR.     

Synergistic electro-co-deposition and molecular mixing for reinforcement of multi-walled carbon nanotube in copper

Carbon nanotube-reinforced copper composite powder was prepared by a modified electro-co-deposition method that was carried out on small diameter (3 mm) tip of the cathode. The deposition was done at room temperature and atmospheric pressure. Samples were prepared under constant stirring by a magnetic stirrer. Transmission and scanning electron microscopy confirms the dispersion of multiwalled carbon nanotubes (MWCNT) in the copper matrix. Dispersion of MWCNTs in copper matrix by this method is very easy and the set up can be easily scaled up for the bulk production of MWCNT reinforced copper powder. The method for the fabrication of MWCNT reinforced copper powder; microstructure and morphology of the powder formed are reported.