Sandip Chavhan

Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies.

Sustained release nanoparticulate formulations of Rivastigmine tartrate (RT) were prepared, optimized (using factorial design) and characterized using the biodegradable polymers, PLGA and PBCA as carriers. The pharmacodynamic performances of the nanoparticles (NPs) were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris Water Maze Test. PLGA NPs were prepared by nanoprecipitation technique, while PBCA NPs were prepared by emulsion polymerization technique. Effect of key formulation variables on particle size (PS) and percentage drug entrapment (PDE) of NPs was studied by using factorial design. PLGA NPs showed PS of 135.6±4.2nm and PDE of 74.46±0.76 %, whereas PBCA NPS showed PS of 146.8±2.6nm and PDE of 57.32±0.91%. FTIR and GPC characterization confirmed complete polymerization of n-butyl cyanoacrylate (nBCA) monomer into PBCA. DSC thermograms indicated that RT was dispersed as amorphous state in both PLGA and PBCA NPs. TEM studies indicated that the NPs were spherical. In vitro studies showed 30.86±2.07% and 43.59±3.80% release from PLGA and PBCA NPs in 72h, respectively. Pharmacodynamic study demonstrated faster regain of memory loss in amnesic mice with both PLGA and PBCA NPs when compared to RT solution. This indicates rapid and higher extent of transport of RT into the mice brain and thus shows the suitability of both NPs as potential carriers for providing sustained brain delivery of RT.

Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route

Intranasal drug delivery is known to overcome the blood–brain barrier (BBB) for delivery of drugs to brain. The objective of this study was to prepare risperidone (RSP)-loaded solid lipid nanoparticles (RSLNs) and explore the possibility of brain targeting by nose-to-brain delivery. RSLNs were prepared by solvent emulsification–solvent evaporation method and characterized for drug content, particle size and size distribution, zeta potential, and in vitro drug-release study. The pharmacodynamic study of RSLNs, which was performed by paw test using Perspex platform, showed higher hindlimb retraction time (HRT) values as compared with RSP solution (RS) indicating the superiority of RSLNs over the RS for brain targeting. The pharmacokinetics and biodistribution studies in mice showed that brain/blood ratio 1 h post-administration of RSLNs (i.n.) was found to be 1.36 ± 0.06 (nearly 10- and 5-fold higher) as compared with 0.17 ± 0.05 for RS (i.v.) and 0.78 ± 0.07 for RSLNs (i.v.), respectively. Gamma scintigraphy imaging of mice brain following intravenous and intranasal administration confirmed the localization of drug in brain. This finding substantiates the existence of direct nose-to-brain delivery route for nanoparticles administered to the nasal cavity.

Enhanced antihypertensive activity of candesartan cilexetil nanosuspension: formulation, characterization and pharmacodynamic study.

The objective of the present investigation was to enhance the oral bioavailability of practically insoluble Candesartan cilexetil [CC] by preparing nanosuspension. The nanosuspension was prepared by media milling using zirconium oxide beads and converted to solid state by spray drying. The spray dried nanosuspension of CC [SDCN] was evaluated for particle size, zeta potential, saturation solubility, crystallanity, surface morphology and dissolution behavior. SDCN showed particle size of 223.5±5.4 nm and zeta potential of −32.2±0.6 mV while saturation solubility of bulk CC and SDCN were 125±6.9 μg/ml and 2805±29.5 μg/ml respectively, showing more than 20 times increase in solubility. Differential Scanning Calorimetry [DSC] and X-ray diffraction [XRD] analysis showed that crystalline state of CC remained unchanged in SDCN. Dissolution studies in phosphate buffer pH 6.5 containing 0.7% Tween 20 showed that 53±5% of bulk drug dissolved in 15 min whereas SDCN was almost completely dissolved exhibiting higher dissolution velocity and solubility. Transmission electron microscopy [TEM] revealed that nanocrystals were not of uniform size, and approximately of oval shape. Pharmacodynamic study based on deoxycorticosterone acetate [DOCA] salt model was performed in rats to evaluate in-vivo performance, which showed 26.75±0.33% decrease in systolic blood pressure for nanosuspension while plain drug suspension showed 16.0±0.38% reduction, indicating that increase in dissolution velocity and saturation solubility leads to enhancement of bioavailability of SDCN when compared to bulk CC suspension. Thus, the results conclusively demonstrated a significant enhancement in antihypertensive activity of candesartan when formulated as nanosuspension.

Solid lipid nanoparticles and nanosuspension formulation of Saquinavir: preparation, characterization, pharmacokinetics and biodistribution studies

Solid lipid nanoparticles (SLNs) and nanosuspensions (NSs) have shown great promise for improving bioavailability of poorly water-soluble drugs. This study was aimed to develop SLNs and NS of Saquinavir (SQ) for improvement in bioavailability. These formulations were characterized and their pharmacokinetics and biodistribution in mice were evaluated. Saquinavir-loaded SLNs (SQSLNs) showed particle size 215 ± 9 nm and entrapment efficiency 79.24 ± 1.53%, while solid-state studies (differential scanning calorimetry and X-ray diffraction) indicated entrapment of the drug in SLNs. Saquinavir NS (SNS) showed particle size 344 ± 16 nm with fourfold increase in saturation solubility and its solid-state studies showed reduction in crystallinity. Pharmacokinetics and biodistribution studies of orally administered SQSLN and SNS in mice exhibited higher plasma level concentration compared to saquinavir microsuspension (SMS). The relative bioavailabilities for SNS and SQSLN were 37.39% and 66.53%, respectively, compared to 18.87% bioavailability obtained after administration of SMS, indicating suitability of nanoparticulate formulations for improving bioavailability.

Solid lipid nanoparticles and nanosuspension of adefovir dipivoxil for bioavailability improvement: formulation, characterization, pharmacokinetic and biodistribution studies

The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability. SLNs were prepared by solvent injection method while NS was prepared by pearl milling method. The prepared formulations were characterized for physicochemical parameters such as particle size, ζ potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC). Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations. The SLNs showed particle size of 267 ± 18 nm and entrapment efficiency of 73.5 ± 2.12%. The particle size obtained for NS was 393 ± 13 nm against 710 ± 70 μm for bulk drug, which led to significant improvement in saturation solubility. DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases. Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug. Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach. The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection. The relative bioavailability for adefovir NS and SLN were 52.46% and 78.23% respectively compared to 34.34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability. SLNs were found to performed better as compared to NS for improving the bioavailability of AD.

Simvastatin nanoemulsion for improved oral delivery: design, characterisation, in vitro and in vivo studies.

Abstract Simvastatin is poorly bioavailable as it is practically insoluble in water and shows dissolution rate-limited absorption. Therefore, the present study was aimed at preparing nanoemulsion (NE) of simvastatin for improving its solubility and/or dissolution rate for enhancing its bioavailability. The NEs were evaluated for particle size (PS), zeta potential, transmission electron microscopy (TEM), viscosity, in vitro release and stability studies. The optimised NE showed PS of 132  ±  9 nm and zeta potential of 17.1 ± 1.2 mV. TEM studies demonstrated spherical shape and size of the globules. In vitro release studies showed increased dissolution rate of NE compared with plain drug (PD). Pharmacokinetic studies showed relative bioavailability of simvastatin NE was 369.0% with respect to PD suspension. Pharmacodynamic studies conducted in hyperlipidemic rats showed that significant decrease in the total cholesterol and triglyceride levels for NE as compared with PD proving improvement in bioavailability. In conclusion, NE has great potential for improving bioavailability of poorly water-soluble drugs like simvastatin.