Showing papers by "Dr. Hari Singh Gour University published in 2006"

Formulation and in vitro, in vivo evaluation of extended- release matrix tablet of Zidovudine: Influence of combination of hydrophilic and hydrophobic matrix formers

Abstract: The aim of the present study was to prepare and characterize extended-release matrix tablets of zidovudine using hydrophilic Eudragit RLPO and RSPO alone or their combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type I dissolution apparatus. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. Furthermore, the in vitro and in vivo newly formulated sustained-release zidovudine tablets were compared with conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro drug release study revealed that either Eudragit preparation was able to sustain the drug release only for 6 hours (94.3%±4.5% release). Combining Eudragit with ethyl cellulose sustained the drug release for 12 hours (88.1%±4.1% release). Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. In vivo investigation in rabbits showed sustained-release pharmacokinetic profile of zidovudine from the matrix tablets formulated using combination of Eudragits and ethylcellulose. In conclusion, the results suggest that the developed sustained-release tablets of zidovudine could perform therapeutically better than conventional dosage forms, leading to improve efficacy and better patient compliance.

Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers

Abstract: The present study was aimed at developing and exploring the use of mannosylated dendritic architecture for the selective delivery of an anti-tuberculosis drug, rifampicin (RIF) to alveolar macrophages (AM). The mannosylated dendritic architecture was synthesized and characterized by using IR and NMR spectroscopy. RIF was efficiently loaded into mannosylated dendrimer using dissolution method. Various physicochemical and physiological parameters such as UV, SEM, DSC, drug loading, solubilization, pH dependent in-vitro release, hemolytic toxicity, phagocytic AM uptake and cytotoxicity concerning the mannosylated dendrimer were evaluated. RIF loaded mannosylated dendrimer reduced release rate of drug in pH 7.4, hemolytic toxicity and cytotoxicity; whereas enhanced drug release in pH 5.0 and AM uptake was observed. The present novel dendritic system displayed suitability in terms of biocompatibility and site-specific delivery of antitubercular drug RIF.

Mannosylated niosomes as adjuvant-carrier system for oral mucosal immunization.

Abstract: The aim of the present study was to develop mannosylated niosomes as oral vaccine delivery carrier and adjuvant for the induction of humoral, cellular, and mucosal immunity. Tetanus toxoid (TT) loaded niosomes composed of sorbiton monostearate (Span 60), cholesterol, and stearylamine were prepared by the reverse-phase evaporation method. They were coated with a modified polysaccharide o-palmitoyl mannan (OPM) to protect them from bile salts caused dissolution and enzymatic degradation in the gastrointestinal tract and to enhance their affinity toward the antigen presenting cells of Peyer's patches. Prepared niosomes were characterized in vitro for their size, shape, entrapment efficiency, ligand binding specificity, and stability in simulated gastric fluid and simulated intestinal fluid. OPM-coated niosomes were found to more stable in simulated gastrointestinal conditions. The immune stimulating activity was studied by measuring serum IgG titer, IgG2a/IgG1 ratio in serum, and sIgA levels in intestinal and salivary secretions following oral administration of niosomal formulations in albino rats. The results were compared with alum-adsorbed TT following oral and intramuscular administration, and it was observed that OPM-coated niosomes produced better IgG levels as compared to plain uncoated niosomes and alum-adsorbed TT upon oral administration. Oral niosomes also elicited a significant mucosal immune response (sIgA levels in mucosal secretions). The developed formulations also elicited a combined serum IgG2a/IgG1 response, suggesting that they were capable of eliciting both humoral and cellular response. The study signifies the potential of OPM-coated niosomes as an oral vaccine delivery carrier and adjuvant. The proposed system is simple, stable, and cost-effective and may be clinically acceptable.

Optimizing efficacy of amphotericin B through nanomodification.

Abstract: Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB- deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical efficacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifications of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specific drug delivery.

Reduced hematopoietic toxicity, enhanced cellular uptake and altered pharmacokinetics of azidothymidine loaded galactosylated liposomes

Abstract: In order to target liposomes to the lectin receptors present on macrophages, galactosylated liposomes were prepared and characterized in vitro. O-palmitoylgalactose (OPG) for liposomal coating was synthesized by esterification of galactose with palmitoyl chloride. The galactose binding Ricinus communis lectin was employed as a model system for the determination of in vitro ligand binding capacity. Cellular drug uptake studies were performed using alveolar macrophages. Hematological changes, bone marrow toxicity, plasma and tissue distribution study of free, uncoated plain liposomal and galactosylated liposomal encapsulated azidothymidine (AZT) were determined following a bolus intravenous injection in Sprague–Dawley rats. Lectin (R. communis) carbohydrate interaction has been utilized for the effective delivery of AZT entrapped in galactosylated vesicles. Aggregation of galactosylated liposomes increased as lectin concentration was increased from 5 to 30 μg/ml. Cellular uptake of galactosylated liposomal ...

Preliminary Immunomodulatory Activities of the Aqueous Extract of Terminalia chebula.

Abstract: Terminalia chebula. (Gaertn.) Retz. (Combretaceae), a plant widely used in the traditional medicinal systems of India, has been reported to possess antibacterial, laxative, antioxidant, and diuretic activities. In the current study, the aqueous fruit extract of Terminalia chebula. has been investigated for its effect on cell-mediated and humoral components of the immune system in mice. Administration of Terminalia chebula. extract produced an increase in humoral antibody (HA) titer and delayed-type hypersensitivity (DTH) in mice. It was concluded that the Terminalia chebula. extract is a promising drug with immunostimulant properties.

Preparation and Characterization of Oxybenzone-Loaded Gelatin Microspheres for Enhancement of Sunscreening Efficacy

Abstract: The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C5 containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.

Spectrophotometric determination of Fexofenadine hydrochloride

Abstract: A simple and sensitive spectrophotometric method has been developed for the determination of fexofenadine hydrochloride in bulk and pharmaceutical dosage forms The method is based on the chloroform-extractable pale yellow colour complex formed by the reaction of fexofenadine with bromothymol blue at pH 26 The chromogen can be estimated at 412 nm against a reagent blank This method obeys Beer's law in the concentration range of 10-50 µg/ml of the drug The optimum reaction conditions and other analytical parameters were also evaluated The proposed method has been successfully applied to the analysis of bulk drugs and their dosage forms

Immunomodulatory Activity of the Ayurvedic Formulation ''Ashwagandha Churna''

Abstract: Immunomodulatory activity was evaluated for “ashwagandha churna,” a reputed Ayurvedic herbal formulation. The experimental paradigms used were cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs (SRBCs) and the neutrophil adhesion test. On oral administration, ashwagandha churna showed a significant increase in neutrophil adhesion and delayed-type hypersensitivity (DTH) response. It is concluded that ashwagandha churna significantly potentiated the cellular immunity by facilitating the footpad thickness response to SRBCs in sensitized rats.

Morphological and biochemical studies on the different developmental stages of a fresh water snail, Lymnaea stagnalis (Lymnaeidae) after treatment with some pesticides.

Abstract: In the present study when the egg masses of Lymnaea stagnalis showing different developmental stages were introduced with the sub lethal concentrations of baygon and nuvan from cleavage to before hatching stages exhibited the development arrest in most of the egg capsules due to deviation in protein fractions in the corresponding development stages in comparison to control groups resulted into high percentage of mortality and low percentage of hatchability in treated groups. Another potent cause of low percentage of hatchability of young snails from their corresponding egg capsules was the phenomenon of polyembryony in nuvan treated egg masses which showed the high rate of mortality due to the lack of metabolites for their progressive development in comparison to control groups. Teratogenesis and deformities in larval stages were also observed in most of the egg capsules which could be correlated with the depletion of most of the protein fractions in the present investigation.

Transport property and structural characterization studies on (1 − x)[0.75AgI:0.25AgCl]:xTiO2 conducting composite electrolyte system

Abstract: Transport property and structural investigation have been carried out on newly synthesized Ag+ ion conducting composite electrolyte system. The composite electrolyte system (1 − x)[0.75AgI:0.25AgCl]:xTiO2, where 0 ⩽ x ⩽ 0.5 (in molar weight fraction) has been synthesized by melt quenching and annealing methods. The chemical compound TiO2 (second phase dispersoid) dispersed in different compositions in a quenched (0.75AgI:0.25AgCl) mixed system/solid solution; this solid solution was used as a first phase host salt in place of AgI. The different preparation routes were adopted for the composite electrolyte system. Composition x = 0.1 exhibited highest conductivity at room temperature. The composite system 0.9[0.75AgI:0.25AgCl]:0.1TiO2 was synthesized at different soaking times by melt quenching method. The system exhibited optimum conductivity at 20 min soaking time (σrt ≈ 1.4 × 10−3 S/cm). The ac conductivity has been measured from Z′–Z″ (Cole–Cole) complex impedance plots using impedance spectroscopic (IS) technique. The electrical conductivity as a function of temperature and frequency has been studied, and activation energy Ea, was calculated from Arrhenius plots for all compositions (0 ⩽ x ⩽ 0.5). The dc conductivity value has been evaluated from Log σ vs. log f plots. Structural characterization studies were carried out by X-ray diffraction (XRD) and differential thermal analysis (DSC) techniques.

Synthesis of 5-Arylidene-2-aryl-3-(benzotriazoloacetamidyl)-1,3-thiazolidin-4-ones (VII) as Analgesic and Antimicrobial Agents.

Abstract: Benzotriazole on reaction with ethyl chloroacetate affords 1, which on treatment with hydrazine hydrate yields 2. Condensation of N'(acetohydrazido)benzotriazole 2 with various carbonyls gives arylidene acetohydrazido benzotriazoles 3 which on cycloaddition with mercaptoacetic acid yields the corresponding 4-thiazolidinones 4. which on reaction with various carbonyl compounds afford 5-arylidene-2-aryl-benzotriazoloacetamidyl-1,3-thiazolidin-4-ones 5.

SMaRT: A novel approach to gene therapy

Abstract: Spliceosome-mediated RNA trans-splicing is a new technology for gene therapy that exploits the expressed genetic differences between normal and diseased cells. This technology may be applied to a wide range of diseases that involve the expression of unique or mutated genes. Spliceosome-mediated RNA trans-splicing technology can be employed to control the expression of any delivered gene by the presence of the chosen target pre-mRNA.

Microwave‐Assisted Combinatorial Chemistry: The Potential Approach for Acceleration of Drug Discovery

Abstract: In the present scenario, pharmaceutical companies are under pressure to speed-up their drug discovery programmes and to lower the cost of discovering new medicines. Combinatorial chemistry and high through put synthesis are almost well established as potential means of speeding up the drug discovery process, these techniques have been embraced widely by the pharmaceutical industry but there is still more need to speed-up the drug discovery. The use of microwave energy to combinatorial synthesis is one potential way to accelerate drug discovery. The advantages of microwave heating technology to combinatorial chemistry mainly includes dramatically reduced reaction time, increase in purity of resulting products and enhancement of chemical yields. In this review we discuss basic introduction to microwave theory which will enable researchers to understand at a molecular level the fundamental nature of phenomenon which results in heating and covered literature published which reveals advantageous nature of microwaves to combinatorial chemistry.

Deviation of negatively charged protein fractions in the trochophore and veliger larvae by the larvicidal action of baygon in freshwater pulmonate Gyraulus convexiusculus (Planorbidae).

Abstract: In the present investigation egg capsules of Gyraulus convexiusculus were treated with different concentrations of baygon. A dose and duration dependent deviations in the number of negatively charged protein fractions in the trochophore and veliger larval stages were observed. It resulted into anomalies in the morphogenesis and organogenesis of corresponding larval stages. Most of the protein bands showed the decrease in the protein positive intensities in comparison to control. This suggested that baygon causes larval toxicity in Gyraulus convexiusculus.