Showing papers by "Roop K. Khar published in 2011"
TL;DR: Data demonstrate that chitosan conjugate nano-prodrugs may be used as sustained polymeric prodrugs for enhancing bioavailability and solubility in atorvastatin.
96 citations
TL;DR: This paper attempts to unveil the multidimensional theranostic aspects of multifunctional metallic nanoparticles (MNPs) including passive and active targeting (HER2, Folate, Angiogenesis etc.) as well as the RES escaping approach.
Abstract: The targeted delivery of theranostic agents to the cancer cells is one of the major challenges and an active field of research in the development of cancer chemotherapeutic approaches. Theranostic metallic nanoparticles (TMNPs) have garnered increasing attention in recent years as a novel tool for theranostic application such as imaging, diagnosis, and therapeutic delivery of active agents to tumour specific cells. This paper attempts to unveil the multidimensional theranostic aspects of multifunctional metallic nanoparticles (MNPs) including passive and active targeting (HER2, Folate, Angiogenesis etc.) as well as the RES escaping approach. Special attention is given to the theranostic application of MNPs in oncology. Patents issued by the US office in this nanotechnological arena are also included emphasising the importance of MNPs in current cancer treatment/imaging research scenario. Keeping in mind the blooming research in clinical application directed nanotechnology; toxicity concerns related with MNPs are. also discussed, in element.
81 citations
TL;DR: PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of pac litaxel as observed by in vivo toxicity studies.
Abstract: The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution, surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The mean particle size of SLNs was 96 ± 4.4 nm with a low polydispersity index of 0.162 ± 0.04 and zeta potential of 39.1 ± 0.8 mV. The drug entrapment efficiency was found to be 75.42 ± 1.5% with a loading capacity of 31.5 ± 2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma and tissues was ten- and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high mean C
max (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of paclitaxel as observed by in vivo toxicity studies.
80 citations
TL;DR: Ex vivo and in vivo studies demonstrate that Nanoplexes are potentially useful as ocular drug carriers and the uptake mechanism postulated was adsorptive-mediated endocytosis and opening of the tight junctions between epithelial cells.
66 citations
TL;DR: The validated method was successfully applied to quantify THQ in dissolution medium as well as oral in vivo pharmacokinetic study of THQ suspension and THQ- solid lipid nanoparticle (THQ-SLN) formulation, and results indicate that the SLN significantly increased plasma concentrations and retention within the systemic circulation.
Abstract: Thymoquinone (THQ) is known for its neuroprotective and anti-convulsant properties in preclinical studies. We herewith describe a simple, rapid, selective, sensitive and stability-indicating UPLC method for the estimation of THQ and its application to biopharmaceutical studies such as in vitro release from nanoparticulate system and in vivo pharmacokinetic study. The method employed gradient elution using a Waters Acquity HSS-T3 C18 (100 × 2.1 mm, 1.8 µm) UPLC column. The mobile phase consisted of water and acetonitrile, pumped at a flow rate of 0.5 mL/min. The injection volume was 5 µL and THQ was monitored at 294 nm wavelength with a total run time of 6 min. In solution as well as in plasma, the method was found to be linear (r ≥ 0.998), precise (CV ≤ 2.45%) and accurate (recovery ≥ 84.8%) in the selected concentration range of 0.1–0.8 µg/mL. Forced degradation studies revealed that THQ undergoes degradation under acidic, basic, oxidation and UV light stress conditions. However, the developed UPLC method could effectively resolve degradation product peaks from THQ. Further, no interference was found at the retention time of THQ from any plasma components, indicating selectivity of the developed method. For solutions, the limits of detection and quantitation of the method were found to be 0.001 and 0.0033 µg/mL, respectively; while in plasma they were 0.006 and 0.02 µg/mL, respectively. The validated method was successfully applied to quantify THQ in dissolution medium as well as oral in vivo pharmacokinetic study of THQ suspension and THQ- solid lipid nanoparticle (THQ-SLN) formulation. A 2-fold increase in the relative bioavailability was observed with the THQ-SLN compared with THQ. The results indicate that the SLN significantly increased plasma concentrations and retention within the systemic circulation. Copyright © 2010 John Wiley & Sons, Ltd.
42 citations
TL;DR: In this paper, a mucoadhesive alginate microspheres of acyclovir were prepared to prolong the gastric residence time using a simple emulsification phase separation technique.
Abstract: In the present study, mucoadhesive alginate microspheres of acyclovir were prepared to prolong the gastric residence time using a simple emulsification phase separation technique. The particle size of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope and mastersizer. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (70.60 ± 2.44 µm). The results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and decreased with increase in stirring speed. The entrapment efficiency was found to be in the range of 51.42−80.46%. The concentration of the calcium chloride (% w/v) of 10% and drug–polymer ratio of 1:4 resulted in an increase in the entrapment efficiency and the extent of drug release. The optimized alginate microspheres...
37 citations
TL;DR: The validated HPTLC method could be used to carry out pharmacokinetic studies of the TBS from novel drug delivery systems and the maximum plasma concentration was found to be 5875.03 ± 114 ng mL(-1), which is significantly higher than the maximum saliva concentration.
Abstract: Terbutaline sulfate (TBS) was assayed in biological samples by validated HPTLC method. Densitometric analysis of TBS was carried out at 366 nm on precoated TLC aluminum plates with silica gel 60F254 as a stationary phase and chloroform–methanol (9.0:1.0, v/v) as a mobile phase. TBS was well resolved at RF 0.34 ± 0.02. In all matrices, the calibration curve appeared linear (r2 ⩾ 0.9943) in the tested range of 100–1000 ng spot−1 with a limit of quantification of 18.35 ng spot−1. Drug recovery from biological fluids averaged ⩾95.92%. In both matrices, rapid degradation of drug favored and the T0.5 of drug ranged from 9.92 to 12.41 h at 4 °C and from 6.31 to 9.13 h at 20 °C. Frozen at −20 °C, this drug was stable for at least 2 months (without losses >10%). The maximum plasma concentration (Cpmax) was found to be 5875.03 ± 114 ng mL−1, which is significantly higher than the maximum saliva concentration (Csmax, 1501.69 ± 96 ng mL−1). Therefore, the validated method could be used to carry out pharmacokinetic studies of the TBS from novel drug delivery systems.
32 citations
TL;DR: Curve fitting proved that the drug release from the tablets followed the Higuchi model, and in vitro bacterial inhibition studies illustrated that the released drugs were able to diffuse through agar medium, inhibiting MTZ sensitive Bacteroides fragilis.
Abstract: The aim of this study was to develop a novel colon targeted matrix tablet containing Metronidazole (MTZ) as model drug. Matrix tablets were prepared using Assam Bora rice starch, which is essentially a natural polymer, by wet granulation technique. The granules prepared were subjected to evaluation for angle of repose, bulk density, compressibility index, Hausner's ratio, total porosity, and drug content. The developed tablets were also analysed for thickness, diameter, weight variation tests, tablet crushing strength, friability, and in vitro release studies. The granules displayed satisfactory flow properties, compressibility, Hausner's ratio and drug content. Almost all the tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house developed specifications for the tested parameters. Drug release study confirmed to the initial fast release in the acidic environment of surface adhered drug followed by slow release in alkaline media subsequently leading to fast and major drug release in the caecal content. Furthermore, the release of drug was unaffected by the hostile environment of GIT which can be ascribed to microbial degradation, promptly followed by enzymatic degradation. Curve fitting proved that the drug release from the tablets followed the Higuchi model. In vitro bacterial inhibition studies illustrated that the released drugs were able to diffuse through agar medium, inhibiting MTZ sensitive Bacteroides fragilis. The selected MTZ matrix tablets (F1-F6) had zones of inhibition paralleling those of the marketed formulation.
32 citations
TL;DR: Results indicated the nonirritant and nontoxic nature of the developed formulations of GCV, which could be effective in the treatment of ocular infections by topical instillation.
Abstract: Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dose results in dose-related toxicity including bone marrow suppression and neutropenia. The aim of the present study was to investigate the comparative potential of different mucoadhesive nano formulations for the topical ocular delivery of Ganciclovir. GCV mucoadhesive Nanoemulsions (GCV-NEs), chitosan nanoparticles (GCV-NPs), GCV mucoadhesive niosomal dispersion (GCV-NDs) were prepared by the reverse-phase evaporation technique. All of the three formulations were evenly round in shape with mean particle size in the range of 23-200 nm. These results indicated the nonirritant and nontoxic nature of the developed formulations. The achieved results may be useful for formulation development of GCV, which could be effective in the treatment of ocular infections by topical instillation.
25 citations
TL;DR: The present study describes the feasibility and suitability of stearylamine based SLN produced using a mixture of surfactants to develop a clinically useful system with targeting potential for poorly soluble antineoplastic drugs.
Abstract: The objective of the study was to design and evaluate a solid lipid nanoparticle (SLN) drug delivery system for delivery of paclitaxel. Components of the SLN were lipid (stearylamine) and surfactants (Pluronic F68 and Soya lecithin). The paclitaxel loaded nanoparticles were prepared by a modified solvent injection method. Experiments were carried out with excipients, where surfactants, lipid and drug molar ratios were varied to optimize the formulation characteristics. The in vitro drug release profile from the nanoparticles followed a diffusion controlled mechanism. The modified solvent injection method ensured high entrapment efficiency (approximately 75%), produced smaller, stable nanoparticles with a narrow size distribution and proved to be a reproducible and fast production method. The present study describes the feasibility and suitability of stearylamine based SLN produced using a mixture of surfactants to develop a clinically useful system with targeting potential for poorly soluble antineoplastic drugs.
19 citations
TL;DR: The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa.
Abstract: Current investigation aimed to develop a novel Amiloride loaded mucoadhesive nanoemulsion formulation for nose-to-brain delivery. Furthermore, nasal irritation study and histopathological examination of the nasal mucosa were also carried out to assess nonirritant nature of the nanoemulsion. The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa. Amiloride loaded mucoadhesive nanoemulsion formulations are non toxic on nasal mucosa and can be administered by intranasal route for effective treatment of epilepsy.
Patent•
26 Apr 2011TL;DR: In this paper, a pharmaceutical composition in the form of self nano emulsifying drug delivery formulation comprising curcuminoids is presented, which shows an enhanced drug loading ability, better stability and an improved bioavailability.
Abstract: The present invention discloses a pharmaceutical composition in the form of self nano emulsifying drug delivery formulation comprising curcuminoids. The pharmaceutical composition of the present invention shows an enhanced drug loading ability, better stability and an improved bioavailability. The composition of the present invention comprises of a pharmaceutically effective amount of a curcuminoid, an oil phase, a surfactant and a co surfactant.
TL;DR: In this paper, a thin-layer chromatographic method for analysis of irinotecan both as bulk drug and in marketed injectables has been developed and validated as per ICH guidelines.
Abstract: A simple, sensitive, precise, and accurate stability-indicating high performance thin-layer chromatographic method for analysis of irinotecan both as bulk drug and in marketed injectables has been developed and validated as per ICH guidelines. Chromatographic separation was achieved on LiChrospher aluminum plates precoated with silica gel 60F254 as stationary phase. The solvent system consisted of acetone–ethyl acetate–acetic acid 8.5:1.5:0.1 (v/v/v) and this system was found to give compact spots for irinotecan at RF value of 0.31 ± 0.02. Densitometric analysis was performed in the absorbance at 366 nm. The linear regression analysis for the calibration plots showed good linear relationship with r2 = 0.9973 ± 0.0013 in the concentration range of 50–500 ng/spot. The method was validated for precision, accuracy, recovery, and specificity. The % recovery (94.63–101.40%) and precision (≤4.30) were found to be satisfactory. Irinotecan was subjected to acid and alkali hydrolysis, oxidation, thermal, and ultrav...
TL;DR: Mucoadhesive chitosan microspheres of acyclovir were prepared to prolong the gastric residence time using simple emulsification phase separation technique in this article.
Abstract: Mucoadhesive chitosan microspheres of acyclovir were prepared to prolong the gastric residence time using simple emulsification phase separation technique. The particle morphology of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (31.62 ± 4.64). The entrapment efficiency was found to be in the range of 40.24 to 67.29%. The concentration of the glutaraldehyde (25%v/v) as a cross-linker 2 ml and drug polymer ratio of 1:2 caused an increase in the entrapment efficiency and the extent of drug release. The optimized chitosan microspheres were found to possess good bioadhesion (79.89 ± 1.01%). The gamma-scintigraphy study showed the gastric residence time of more than 6 hours which revealed that optimized formulation could be a good c...