Release Of Norfloxacin Research Articles

Simultaneous photoactivation of a fluoroquinolone antibiotic and nitric oxide with fluorescence reporting.

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF-NO, which is inactive at the typical minimum inhibitory concentration of NF. Irradiation of NF-NO with visible blue light triggers the simultaneous release of NF and nitric oxide (NO). The photouncaging process is accompanied by the revival of the typical fluorescence emission of NF, quenched in NF-NO, which acts as an optical reporter. This permits the real-time monitoring of the photouncaging process, even within bacteria cells where antibacterial activity is switched on exclusively upon light irradiation. The mechanism of photorelease seems to occur through a two-step hopping electron transfer mediated by the lowest triplet state of NF-NO and the phosphate buffer ions or aminoacids such as tyrosine. Considering the well-known role of NO as an "unconventional" antibacterial, the NF-NO conjugate may represent a potential bimodal antibacterial weapon activatable on demand with high spatio-temporal control.

Thermo- and pH-responsive cotton gauzes as drug delivery system obtained by gamma radiation and chemical initiator

The grafting of stimuli-responsive polymers into medical devices to create functional materials has attracted the attention of scientific community. The capacity of these polymers to change its conformation reversibly as function of variables of the environment in which it is applied, is well taken into account to create drug delivery systems. Because cotton gauzes are materials of priority use in biomedical area, and they are susceptible to develop biofilm on its surface contaminating skin wounds. This work proposes the modification of cotton gauze with a dual stimuli-responsive copolymer, composed of two monomers such as methacrylic acid and N-isopropylacrylamide, through a grafting copolymerization induced by chemical initiator and gamma radiation. Experimental conditions were evaluated for each method. Grafting was verified by infrared spectroscopy (FTIR-ATR) and scanning electron microscopy as well as its thermal behavior was determined through thermogravimetric analysis. Critical pH was confirmed by potentiometric titrations finding a value of 4.7 for grafted cotton gauzes and their critical temperature ranging between 31 and 34 °C, which was determined by water uptake as function of temperature. The loading and release of norfloxacin were tested, finding that grafted gauzes exhibited affinity for this drug and it is released under simulated physiological conditions of temperature and pH. Norfloxacin-loaded gauzes show their efficiency inhibiting Escherichia coli and Staphylococcus aureus growth in a contaminated environment, at different pH values. This improvement of cotton gauzes can serve as barrier to avoid the formation of biofilm in surgical conditions and for wound healing.

Self emulsifying drug delivery system: norfloxacin model drug

Background Norfloxacin is a synthetic antibacterial fluoroquinolone that is poorly water soluble and active against a wide spectrum of gram-positive and gram-negative aerobic bacteria. The goal of this work was to create a self-nanoemulsion (SNE) as a colloidal dispersed drug delivery system for increasing norfloxacin dissolving rate, while also assuming intestinal lymphatic transport participation for such a nano-size system that would increase norfloxacin oral bioavailability. Methods Depending on the solubility of norfloxacin in various components, several formulations of liquid SNEDDS of the antibiotic were created using oleic acid (oil), tween20 (surfactant), and PEG200 (co-surfactant). To assess the presence of a nanoemulsion region, phase diagram was generated at various oil: surfactant: co-surfactant ratios. Results The in-vitro dissolution profile suggested an optimum norfloxacin SEDD formulation (F1) comprised of oleic acid (10%), tween 20 (45%), and PEG200 (45%), as opposed to commercially available traditional tablets. The F1 formula exhibited thermodynamic stability with a zeta potential of +60.78mV and a droplet size of 57.4nm. The F1 formula revealed an improved dissolving profile as compared to the commercial Tablet of norfloxacin. Conclusion Based on the findings, this study indicated that preparing norfloxacin as a liquid self-nanoemulsifying system improved the solubility and drug release of norfloxacin counteract the inconsistent bioavailability of the commercial tablet.

Impacts of norfloxacin on sewage sludge anaerobic digestion: Bioenergy generation and potential environmental risks

Norfloxacin is a broad-spectrum antibiotic which has been frequently detected in the sewage sludge. However, whether norfloxacin in sewage sludge would affect the anaerobic digestion for bioenergy generation and induce environmental risks remained unclear. Therefore, this study investigated the impact of norfloxacin on sewage sludge anaerobic digestion and evaluated potential environmental risks by exploring related antibiotic resistance genes (ARGs) and norfloxacin transformation pathways. The results showed that norfloxacin at environmental relevant concentration ranges would not significantly affect methane production (p < 0.05) during the sludge anaerobic digestion, as the sludge solubilization and hydrolysis is unaffected. However, the individual methanogenesis process was enhanced with the increase of Methanosaeta abundances. Meanwhile, the increase of norfloxacin concentration will not decrease the removal efficiencies of fluoroquinolones-family ARGs by the anaerobic digestion process. However, the norfloxacin concentration is found to be increased during the anaerobic digestion process, which could probably be due to the desorption from the sludge due to cell lysis. In addition, 13 norfloxacin transformation metabolites were identified with 5 potential norfloxacin degradation pathways being constructed. The metabolites of levofloxacin/ofloxacin could be generated through Eschweiler-Clarke reaction, which may be more toxic than norfloxacin. Thus, the results of this study suggested that although norfloxacin would not affect the bioenergy generation and ARG removal during sludge anaerobic digestion, measures should be taken to deal with the potential environmental risks caused by norfloxacin release and formation of more toxic metabolites.

Biocompatible Drug Delivery System Based on a MOF Platform for a Sustained and Controlled Release of the Poorly Soluble Drug Norfloxacin.

Norfloxacin (NFX), an important antibacterial fluoroquinolone, is a class IV drug according to the biopharmaceutics classification system (BCS) and has low solubility and permeability issues. Such poor physicochemical properties of drug molecules lead to poor delivery and are of serious concern to the pharmaceutical industry for clinical development. We present here a conceptually new approach to deliver NFX, by loading the drug molecule on the porous platform of a biocompatible metal-organic framework (MOF), MIL-100(Fe). The loading of the drug on the MOF leading to NFX@MIL-100(Fe) was characterized by Fourier transform infrared (FTIR), UV-visible spectroscopy, thermogravimetric analyses (TGA), and nitrogen adsorption studies. Controlled experiments resulted in the high loading of the drug molecule (∼20 wt %) along with the desired sustained release. We could further control the release of norfloxacin by coating drug-loaded MIL-100(Fe) with PEG, PEG{NFX@MIL-100(Fe)}. Both drug delivery systems (DDSs), NFX@MIL-100(Fe) and PEG{NFX@MIL-100(Fe)}, were tested for their biocompatibility through toxicity studies. The DDSs are biocompatible and show insignificant cytotoxicity, as revealed by cell viability studies through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Surfactant vesicles for enhanced antitoxoplasmic effect of norfloxacin: In vitro and in vivo evaluations

The goal was to scrutinize niosomes as potential carriers for enhanced efficacy of norfloxacin against Toxoplasma gondii RH strain. This was assessed in vitro and in vivo. Standard niosomes of Span 60 and cholesterol were prepared. Gelucire 48/16 or Tween 80 was incorporated as hydrophilic fluidizer. The prepared vesicles were characterized for shape, size, viscosity and norfloxacin release. The in vitro anti-Toxoplasma was assessed by monitoring tachyzoites viability after incubation with niosomes. In vivo efficacy of niosomes encapsulated norfloxacin was evaluated on infected mice. Transmission electron micrographs showed nano-sized spherical vesicles. Norfloxacin release varied with niosomal composition to show faster liberation in presence of fluidizing agent. The half maximum effective concentration of norfloxacin against tachyzoites (EC50) was significantly reduced after niosomal encapsulation compared with simple drug solution with no significant difference between vesicular formulations. Tachyzoite count in the peritoneal fluid of infected mice was reduced by 45.2, 90.8, 88.3 and 84% after treatment with simple drug dispersion, standard niosomes, Gelucire containing and Tween containing vesicles, respectively compared to infected untreated mice. These results correlate with the in vitro data and reflects the efficacy of niosomes. The study introduced surfactant vesicles as a tool for enhanced efficacy of norfloxacin against toxoplasma.

Magnetic Fe3O4@ZIF-8 nanoparticles as a drug release vehicle: pH-sensitive release of norfloxacin and its antibacterial activity

Metal-organic frameworks (MOFs) have a high specific surface area and inherent biodegradability due to their unique structure and composition. As well, owing to the properties of nanomaterials and especially their magnetic features, Fe3O4 nanoparticles and MOFs composite materials have great potential in the design and application of drug release. The present work: firstly, investigated norfloxacin loading in magnetic metal organic framework (Fe3O4@ZIF-8); and secondly, studied the release of norfloxacin and its antibacterial activity. Results showed the release efficiencies reached 97 % at 310 K after 84 h (pH 7.4). Drug release behavior was tested at various pH levels and it was found that Fe3O4@ZIF-8 has pH-sensitive properties. Furthermore, the release model calculation illustrated that the release process fitted well to the Bhaskar model. The magnetic properties of Fe3O4@ZIF-8 confirmed that the composite has potential application for a targeted drug delivery system. The mechanism of pH-responsive norfloxacin release was combined with diffusion, ion exchange and electrostatic repulsion. Furthermore, the antibacterial activities of Fe3O4@ZIF-8 and NOR-Fe3O4@ZIF-8 were tested against Escherichia coli. Results showed that Fe3O4@ZIF-8 had good biocompatibility while NOR-Fe3O4@ZIF-8 can deter or inhibit the actions of microorganisms.

Improving the Bioactivity of Norfloxacin with Tablets Made from Paper.

(1) Background: Many drugs possess poor bioavailability, and many strategies are available to overcome this issue. In this study, smartFilm technology, i.e., a porous cellulose matrix (paper), in which the active compound can be loaded onto in an amorphous state was utilised for oral administration to improve the solubility and bioactivity of a poorly soluble BSC class IV antibiotic. (2) Methods: Norfloxacin was used as the model drug and loaded into commercially available paper. The resulting norfloxacin-loaded smartFilms were transformed into smartFilm granules via wet granulation and the resulting norfloxacin-loaded smartFilm granules were transformed into norfloxacin-loaded tablets made from paper, i.e., smartFilm tablets. The crystalline state of norfloxacin was investigated, as well as the pharmaceutical properties of the granules and the tablets. The bioactivity of the smartFilm tablets was assessed in vitro and ex vivo to determine the antibacterial activity of norfloxacin. The results were compared to a physical mixture tablet that contained non-loaded paper granules and equal amounts of norfloxacin as a crystalline powder. (3) Results: Norfloxacin-loaded smartFilm granules and norfloxacin-loaded smartFilm tablets contained norfloxacin in an amorphous state, which resulted in an improved and faster release of norfloxacin when compared to the physical mixture tablet. The bioactivity was up to three times higher when compared to the physical mixture tablet. The ex vivo model was demonstrated to be a useful tool that allows for a fast and cost-effective discrimination between "good" and "bad" formulations. It provides realistic physiological conditions and can therefore yield meaningful, additional biopharmaceutical information that cannot be assessed in classical in vitro experiments. (4) Conclusions: smartFilm tablets are a promising, universal, industrially feasible and cost-effective formulation strategy for improved solubility and enhanced bioactivity of poorly soluble drugs.

Formulation and Evaluation of Norfloxacin Ocular In-situ Gel

The study aims to prepare and evaluate the in situ Norfloxacin gel for the treatment of Conjunctivitis. The pronounced fluctuations and repeated administration of conventional eye drops are the main disadvantages of ophthalmic drug delivery. The ocular in situ gelling system is designed to achieve a prolonged therapeutic effect by improving residence time at the application site. Infrared spectroscopy studies of Norfloxacin, Sodium alginate, Gellan gum, and HPMC K4M alone and their physical mixture revealed that Norfloxacin is compatible with all the polymers used. The Ophthalmic in situ gelling system of Norfloxacin was successfully formulated using different gelling agents viz. Sodium alginate, Gellan gum, and HPMC K4M are viscosity-enhancing agents. Prepared in situ gels were subjected to evaluation such as visual appearance, pH, and drug content. All formulations were found transparent and clear, the pH of the formulations was between 7.1 to 7.4, and drug content was found within 95-98% in all in situ gelling systems. All the formulations showed instantaneous gelation when contacted with simulated tear fluid. The viscosity of all formulations decreased as the shear rate increased, indicating the pseudoplastic fluid's character. In vitro release of Norfloxacin from the prepared formulations was studied for 6 hours. Results reveal that all formulations exhibited sustained release of the drug from the gelrite polymeric network over 6 hrs. The stability studies confirmed that in situ gelling formulations of Norfloxacin remained more stable at ambient temperature and humidity. The present work was a satisfactory preliminary study in developing in situ gelling systems of Norfloxacin.&#x0D; Keywords: Conjunctivitis, Norfloxacin, in situ gel, Sodium alginate, sustained release.

β-Carboline-Norfloxacin Nanoconjugates as Antibacterial Nanophotocages for the Delivery of Norfloxacin and Singlet Oxygen

Herein, we demonstrate the design and synthesis of a single-component prodrug [β-carboline-benzothiazole-norfloxacin (CB-NFX)] for the cocktail release of therapeutics that enables spatiotemporal control over bacterial growth. With the help of in silico studies, the prodrug was designed based on the β-carboline photoremovable protecting group, caging the acid functionality of norfloxacin (NFX) antibiotic. We have formulated nanoparticles of CB-NFX to obtain nanophotocage CB-NFX NPs. These nanoparticles adhere to the bacterial cell wall, followed by the release of NFX and singlet oxygen (1O2) upon visible-light irradiation. The combined effect of the therapeutics shows excellent spatiotemporal control in bacterial inhibition. This concept can be applied to develop other advanced antibacterial biomaterials for combination therapy (drug and 1O2) and find wide applications in antibacterial research.

Unravelling the role of hemp straw derived cellulose in CMC/PVA hydrogel for sustained release of fluoroquinolone antibiotic

Cellulose fibres derived from hemp stalks, a prevalent biowaste in Northern India, were effectively converted into carboxymethyl cellulose (HS-CMC). Novel environmentally benign hydrogels were synthesized from HS-CMC and polyvinyl alcohol (PVA) using citric acid, a green crosslinker employing freeze-drying method. The HS-CMC/PVA hydrogels were successfully used for sustained release of fluoroquinolone antibiotic, norfloxacin. The hydrogels were characterized using FTIR, XRD, FE-SEM, EDS and thermal stability and evaluated for their carbonyl content, swelling ratio, in-vitro drug release behaviour and bactericidal properties. Successful isolation of cellulose from hemp stalks and its conversion into hydrogel with the presence of ester and carbonyl linkages was confirmed by FTIR. Thermal stability was impaired when cellulose fibres were converted into HS-CMC via carboxymethylation, as the crystalline structure was utterly disrupted. For the hydrogel, the equilibrium swelling ratios at pH -1.2 and 7.4 were assessed as 378.4 % and 538.7 %, respectively, higher than reported CMC hydrogels. The norfloxacin (NFX) encapsulated hydrogels exhibited good bactericidal properties with zone of inhibition of 19.2 ± 0.3 mm against E. coli and 16.4 ± 0.4 mm against S. aureus. The in-vitro release of NFX at pH 1.2 was 91 %, higher than pH 7.4 at 82 % with strong adherence to Higuchi kinetics model signifying that the release of NFX is via dissolution and diffusion. The release kinetics at different pH revealed Fickian behaviour establishing the potential of HS-CMC hydrogel for sustained release of norfloxacin.

Customized 3D-printed hollow capsular device filled with norfloxacin-loaded micropellets for controlled-release delivery.

Pharmacotherapy has become more focused on the personalized treatment of patients with various diseases. This field of pharmacology and pharmacogenomics focuses on developing drug delivery systems designed to address the unique characteristics of individual patients. Three-dimensional printing technology can be used to fabricate personalized drug delivery systems with desired release properties according to patient needs. Norfloxacin (NOR)-loaded micropellets (MPs) were fabricated and filled inside a stereolithography (SLA) 3D printing technology-mediated hollow capsular device in accordance with a standard size of 09 (8.4mm length × 2.70mm diameter). The prepared 3D-printed hollow capsular device filled with pristine NOR and NOR-loaded MPs were characterized in terms of both in vitro and in vivo means. MPs with the particle size distribution of 1540.0 ± 26µm showed 95.63 ± 2.0% NOR content with pellet-shaped surface morphology. The in vitro release profile showed an initial lag phase of approximately 30min, followed by the sustained release of NOR from MPs from the 3D-printed hollow capsular device. The pharmacokinetic profile showed prolonged Tmax, AUC, and evidence of good RBA of NOR compared to pure NOR after a single oral administration in the experimental animal model. The overall results confirm the feasibility of SLA-mediated 3D printing technology for preparing customized solid oral unit dosage carriers that can be filled with pure NOR- and NOR-loaded MPs with controlled-release delivery features.

Alginate enriched with phytic acid for hydrogels preparation. Therapeutic applications

In the last decade, numerous innovative strategies have been used to obtain highly efficient synthetic or semi-synthetic biomaterials. Between these innovative biomaterials, hydrogels occupy a distinct place due to their superior biological and physico-chemical characteristics. Alginate is a natural linear polysaccharide with important physico-chemical and biological properties. Recently, we obtained a new hydrogel based on alginate and phytic acid with improved physico-chemical properties. In the present study, the hydrogels previously obtained were tested in terms of their biological properties and possibilities of use in the biomedical field. For this purpose, the hydrogels were loaded with norfloxacin (NRF), an antibacterial compound utilised in the treatment against Gram-negative and Gram-positive organisms. Unfortunately, NRF has low solubility and permeability. In order to provide protection against loss, but also for enhanced bioavailability, and controlled-release of norfloxacin, a drug inclusion complex with cyclodextrin was realized. The effect of complexation on the release profile was highlighted. The addition of NRF to the hydrogel matrices greatly improved the antibacterial activity of the tested compounds. The presence of CD did not affect the homogeneity of the drug distribution. Changes in the polymeric matrix structure were registered after the incorporation of the drug, which were attributed to the relaxation of the network subsequently to the penetration and diffusion of the drug solution simultaneously with the swelling process. The release of NRF from Alg_PA polymeric network has been successfully modulated by the use of CD as a host molecule.

Nanoparticulate ophthalmic drug delivery of norfloxacin to prevent ocular infection after cataract surgery: Evaluation in animal model

Post cataract surgery, patients generally experience bacterial infection called endophthalmitis which is considered as potent blinding complication. This infection arises from the colonization of Staphylococcus epidermidis on the newly implanted lense. To overcome this problem, we developed nanoparticulate ophthalmic drug delivery of Norfloxacin to prevent ocular infection after cataract surgery. Sustained release Norfloxacin loaded polymeric nanoparticles were developed by high pressure homogenization method. The nanoparticles were characterized for particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE), in vitro Norfloxacin release and surface characteristics using scanning electron microscopy (SEM). The optimized nanoparticulate formulation was further used for the development of thermoreversible ophthalmic gel using poloxamer polymer. The formulated ophthalmic gel was evaluated for gelation temperature, pH, bioadhesiveness, and in vitro corneal permeation study. The antibacterial efficacy testing of thermoreversible gel was assessed in animal model (rabbit) infected with Staphylococcus epidermidis. At the end of study period the inhibitory effect of thermoreversible gel was determined on test animals. The antibacterial effects were compared with control group and plain thermoreversible gel (without nanoparticle formulation). The optimized nanoparticulate formulation of Norfloxacin showed slow and gradual sustained release over the period of 72 hours, encapsulation efficiency of between 90.12 to 98.50%, particle size 95–210 nm, PDI 0.18 to 0.212 and zeta potential between 20 to 25 mV. The nanoparticles were found spherical and smooth in nature. The optimized formulation of nanoparticle was used in thermoreversible gel. The results obtained showed that the thermoreversible gel was clear and transparent (prime requirement for ophthalmic product) with high gelling capacity and moderately viscous liquid (1170 cp), highest bioadhesive strength of 2312.90 dyne/cm2. The exvivo corneal study showed excellent permeation through cornea as compare to control sample. Norfloxacin released from thermoreversible gel killed Staphylococcus epidermidis in animal models as compare to control group and showed effect up to 14 days. With these findings, we demonstrate a new and effective system for sustained drug release of Norfloxacin from thermoreversible gel with specific application to prevent ocular infection after cataract surgery.

Effects of norfloxacin on nitrate reduction and dynamic denitrifying enzymes activities in groundwater.

The impact of antibiotics on denitrification has attracted widespread attention recently. Norfloxacin, as a representative of fluoroquinolone antibiotics, is extensively detected in groundwater. However, whether the release of norfloxacin into the groundwater poses potential risks to denitrification remains unclear. In this study, effect of norfloxacin on denitrification was investigated. The results showed that increasing norfloxacin from 0 to 100μg/L decreased nitrate removal rate from 0.68 to 0.44mg/L/h, but enhanced N2O emission by 177 folds. Additionally, 100μg/L of norfloxacin decreased nitrite accumulation by 50.6%. Corresponding inhibition of norfloxacin on bacterial growth, carbon source utilization, electron transport system activity and genes expression was revealed. Furthermore, denitrifying enzyme dynamic monitoring results showed that norfloxacin inhibited nitrate reductase activity, and enhanced nitrite reductase activity to some extent in denitrification process, which was consistent with the variations of nitrate and nitrite. Meanwhile, sensitivity analysis demonstrated that nitrate reductase was more easily affected by norfloxacin than nitrite reductase. Overall, this study suggests that multiple regulation of denitrifying enzyme activity contributes to evaluating the comprehensive effects of antibiotics on groundwater denitrification.

Hybrid Pectin-Liposome Formulation against Multi-Resistant Bacterial Strains.

This work describes the development of a gastroresistant antimicrobial formulation composed of two carriers, pectin and liposomes, intended to improve the efficiency of norfloxacin (NOR) against multi-resistant bacterial strains. The formulations showed physicochemical stability for 180 days (4 °C) in terms of size, polydispersity, and zeta potential of the vesicles, prolonging the in vitro release of NOR for 11 h. The hybrid nanocarriers improved the in vitro antimicrobial activity against different multidrug-resistant bacterial strains, such as Salmonella sp., Pseudomonas aeruginosa, E. coli and Campylobacter jejuni, in comparison to commercial NOR and liposomal suspensions. The in vivo toxicity assay in chicken embryos revealed that the hybrid systems were not toxic in any of the different parameters analyzed, a result also corroborated by the analyses of biochemical biomarkers of the chicken-embryos liver function.

Carbon dots-incorporated pH-responsive agarose-PVA hydrogel nanocomposites for the controlled release of norfloxacin drug

Several hydrogels-based delivery systems are designed and studied in order to meet the requirements in biomedical fields. Herein, the possibility of carbon dots (CDs)-incorporated hydrogel nanocomposites was investigated for the drug release study. Highly fluorescent CDs synthesized from groundnuts using hydrothermal method were characterized with TEM, FTIR, UV–visible and fluorescence spectroscopy. pH-responsive biodegradable hydrogel nanocomposites were synthesized using agarose polymer and agarose–poly(vinyl alcohol) copolymer with the successful integration of CDs. CDs improved the swelling as well as the biodegradation properties of the prepared hydrogel nanocomposites. Structural changes of prepared hydrogel nanocomposites have been characterized using FTIR, SEM and TGA analysis. Hydrogel nanocomposites showed highly porous surface as shown by SEM analysis. In this study, norfloxacin (NFX) was used as a model drug to investigate the in vitro release behavior at two different pH (pH 1.2 and pH 7.4). NFX release from hydrogel nanocomposites followed zero-order kinetics, and Korsemeyer–Peppas model confirmed the release of NFX through erosion of hydrogel nanocomposites. Degradation of hydrogel nanocomposites films was checked using hen egg lysozyme enzyme which confirmed the biodegradable nature of prepared hydrogel nanocomposites films. MTT assay confirmed the nontoxic nature of hydrogel nanocomposites films when treated with blood cells (PBMC).

Development and Optimization of a Floating Multiparticulate Drug Delivery System for Norfloxacin.

Norfloxacin is a synthetic broad-spectrum antibacterial drug having poor bioavailability and pH-dependent solubility. The purpose of the present study was to develop a gastroretentive floating multiparticulate drug delivery system for norfloxacin. Norfloxacin core pellets were prepared using microcrystalline cellulose (MCC) and polyvinylpyrrolidone K30 (PVP K30) by extrusion and spheronization. A 3-level, 3-factor, 17-run experimental Box-Behnken design was adopted to optimize levels of variables in the pellets' formulations. The selected independent variables were amounts of MCC and PVP K30 and spheronizing speed and the dependent variables were aspect ratio and hardness of pellets. Sodium bicarbonate and hydroxypropyl methylcellulose K15M in the ratios of 1:1, 1:2, and 2:1 (w/w) on a dry solid basis were incorporated into the norfloxacin pellets and they were further coated with Eudragit RL 100 using a fluidized bed processor to obtain weight gain of 5%, 10%, and 15% w/w. The fourier transform infrared spectrum, scanning electron microscopy, physical characterization, particle size distribution analysis, floating studies, and in vitro drug release studies of the pellets were evaluated. Among the floating multiparticulate pellets batches, batch B-22 was found to be optimized based on the criteria of attaining the minimum floating lag time (<10 min) and the maximum value of drug released 82.11% in 8 h. The percentage drug release for batches B-21 and B-23 was 91.12% in 5 h and 60.67% in 8 h, respectively. The drug release studies indicated that as the Eudragit RL 100 polymer coat increases the drug release decreases, producing sustained release of norfloxacin. The floating studies revealed that 70%-90% of pellets remained floating for up to 8 h. All the batches have excellent flow properties with angle of repose in the range of 25.5±0.49° to 28.02±0.30°, and Carr's index and Hausner's ratio in the range of 5% to 15% and 1.05±0.3 to 1.14±0.3, respectively. The significant outcome obtained in the study is that such an approach can be effectively employed for improvement of the bioavailability of drugs having poor absorption in the lower part of the gastrointestinal tract with enhanced therapeutic efficacy.

Layered double hydroxide and microwave assisted functionalized carbon based nanocomposites as controlled release vehicle for antibiotics

In this work, the preparation of new composite from layered double hydroxide (LDH) and surface modified carbon (AC) was elaborated. The basic carbon was obtained by carbonizing Ipomoea carnea stems at 500 °C. The LDH compound was furthermore intercalated with antibiotic molecule norfloxacin (NOR). The chemically activated functionalized carbon particles had surface negative charge which helped in intense interaction with LDH basal positive charges. The prepared nanocomposites were characterized by powder XRD, FT−IR, FE−SEM with EDS, TGA, Zeta potential and BET surface specific area. Powder XRD and SEM studies proved that LDH was deposited over the AC surface homogeneously. The increase of the basal spacing from 0.78 nm to 1.33 nm indicated that not all LDH sheets were intercalated by NOR. Additionally, the water dispersional stability test has shown remarkable advantage compared to simple LDH. The thermal analysis results further showed a good improvement of NOR stability after intercalation into AC−LDH nanocomposite. The release behavior of NOR from the nanocomposite and its antibacterial activity were also investigated. The gradual release of NOR from AC−LDH−NOR nanocomposite suggests its prospective application as an effective delivery system for prolonged drug release.

Biocompatible nanocomposite of carboxymethyl cellulose and functionalized carbon–norfloxacin intercalated layered double hydroxides

In recent years, the development of systems with progressive drug release properties, which is an effective technique for the use of drugs, has aroused great interest in the field of controlled release formulations. In this work, hybrid materials containing citric acid cross–linked carboxymethyl cellulose (CMC) and norfloxacin (NOR) intercalated layered double hydroxide (LDH) deposited over the surface of functionalized carbon (AC) were prepared. The synthesized CMC@AC–LDHNOR nanohybrids were characterized using different techniques and in vitro NOR release behaviors were investigated in phosphate buffer saline, pH 7.4 at 37 °C. On the basis of the release profiles, it was found that NOR release was delayed when it was intercalated in AC–LDH which in presence of modified CMC decreases further. The nanohybrids indicated enhancement of antibacterial activity against gram–negative and gram–positive bacteria. The MTT assay showed their non–toxic behavior against ovarian normal epithelial and cancer cells, suggesting their potential use as drug carriers.