[Development of Prediction System for Drug Absorption after Intranasal Administration Incorporating Physiologic Functions of Nose -Estimation of in Vivo Drug Permeation through Nasal Mucosa Using in Vitro Membrane Permeability].

The nasal drug application has drawn much attention as the strategy for the delivery route of many drug modalities such as the poorly absorbed drugs, peptides, nucleic acid, and central nervous system drugs. The absorption of drug after intranasal (IN) application depends on the nasal residence time of applied drug, affected by mucociliary clearance (MC). MC is a decisive factor in the nasal absorption of drug. We describe the establishment of in vitro evaluation system of nasal MC via the moving velocity of a marker particle on nasal mucosa, and the development of the pharmacokinetic model to which in vitro parameters on nasal MC was incorporated to enable the prediction of drug absorption after IN application. Moreover, the pharmacokinetics of norfloxacin after IN application was investigated using MC-modified rats pretreated with MC modulators. Nasal absorption fluctuated due to changes in the nasal residence time of drug in response to changes in MC. The prediction system enables quantitative evaluation of changes in drug absorption associated with MC fluctuations. In addition, for a precise prediction system for drug absorption after IN application from the drug absorption model, the relationships between in vitro drug permeability through Calu-3 layers, in vivo transnasal permeation of drug and in vivo bioavailability after IN application were evaluated. The significant correlations between these parameters were obtained, suggesting that transnasal permeability and drug absorption after IN application can be predicted from in vitro membrane permeability.

Co-delivery of norfloxacin and tenoxicam in Ag-TiO2/poly(lactic acid) nanohybrid.

A nanohybrid formulation of silver­titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO2/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO2 consists of a cubic phase of Ag with two phases of TiO2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO2/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO2/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.

Synthesis and Design of Norfloxacin drug delivery system based on PLA/TiO2 nanocomposites: Antibacterial and antitumor activities.

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.

Determination of norfloxacin in urine and pharmaceutical samples using terbium doped zinc sulphide nanomaterials-sensitized fluorescence method.

Highly crystalline polyethylene glycol (PEG) coated Tb3+ doped ZnS nanoparticles have been synthesized and successfully used for norfloxacin sensing. The crystallographic and morphological analyses of PEG coated Tb3+ doped ZnS nanoparticles were performed by X-ray diffraction and Transmission electron microscopy, respectively. The confirmation of Tb3+ doping in ZnS host matrix was done by emission spectroscopy and energy dispersive X-ray spectroscopy. Further, the interaction of norfloxacin with PEG coated Tb3+ doped ZnS nanomaterials was confirmed by optical analysis: spectrophotometrically and spectrofluorimetrically. Norfloxacin sensing was measured by luminescence intensity which increased with increase in concentration of norfloxacin in range from 2.0 × 10-9-8.0 × 10-7 mol L-1, with its correlation coefficient 0.9991. The detection limit of proposed method was 0.05 × 10-9 mol L-1. The developed luminescence method was successfully applied for the determination of norfloxacin using PEG coated Tb3+ doped ZnS nanoparticles in urine and pharmaceutical samples.

Binary and ternary complexes of norfloxacin to improve the solubility of the active pharmaceutical ingredient.

AIM: Binary and ternary complexes with hydroxypropyl-ß-cyclodextrin (HPßCD), using glutamic acid (GA), proline or lysine as the third component, were developed to increase the solubility and the dissolution rate of norfloxacin (NOR). METHODS/RESULTS: Complexation was evaluated by phase solubility studies, obtaining the highest NOR solubility with GA and HPßCD. Thermal analysis suggested that different kinds of interactions occur among NOR, HPßCD and each amino acid, and when the systems were prepared by kneading or by means of freeze-drying technique. Dissolution studies, performed on simulated gastric fluid and subsequent simulated intestinal fluid, showed the highest rate of NOR from NOR-HPßCD-GA. CONCLUSION: NOR:HPßCD:GA was the best approach for improving the bioavailability of NOR.

Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity.

Nanosponges are a novel class of hyperbranched cyclodextrin-based nanostructures that exhibits remarkable potential as a drug host system for the improvement in biopharmaceutical properties. This work aims the development of cyclodextrin-based nanosponge of norfloxacin to improve its physicochemical characteristics. ß-cyclodextrin was used as base and diphenyl carbonate as crosslinker agent at different proportions to produce nanosponges that were evaluated by in vitro and in vivo techniques. The proportion cyclodextrin:crosslinker 1:2 M/M was chosen due to its higher encapsulation efficiency (80%), revealing an average diameter size of 40 nm with zeta potential of -19 mV. Norfloxacin-loaded nanosponges exhibited higher passage of norfloxacin in comparison to norfloxacin drug alone by Ussing chamber method. The nanosponge formulation also revealed a mucoadhesive property that could increase norfloxacin absorption thus improving its antibiotic activity in an in vivo sepsis model. Therefore, nanosponges may be suitable carrier of norfloxacin to maximize and facilitate oral absorption.

Synthesis, Characterization and Antimicrobial Evaluation of Lipid Based Norfloxacin Prodrug.

BACKGROUND: Fluoroquinolones, the synthetic antibacterial agents are being successfully utilized against bacterial infections, since the time immemorial. Despite of enormous useful features, these drugs are associated with some limitations also. Large number of efforts has been made by various scientists to improve pharmacokinetic properties of these drugs and hence, to overcome the limitations associated with them. OBJECTIVES: The aim of this paper is to introduce a novel scheme for synthesis of prodrug with improved pharmacokinetic properties i.e., lipophilicity and consequently, modified bioavailability of norfloxacin. METHODS: Fatty acid hydrazide of selected fatty acid was synthesized followed by preparation of 5-formyl salicylamide. N-Mannich base of norfloxacin was synthesized by reacting norfloxacin with 5-formyl salicylamide. The prodrug was obtained by covalently coupling this N-Mannich base of norfloxacin with fatty acid hydrazide. The synthesized lipid based prodrug was evaluated for partition coefficient by shake flask method and screened for antimicrobial activity against selected strains. Drug content determination and in vitro dissolution studies utilizing HPLC were also carried out. RESULTS: The synthesized prodrug was found to exhibit improved partition coefficient (1.15) when compared with parent drug, norfloxacin (0.46). The results of antimicrobial evaluation indicate promising antibacterial and antifungal activity. CONCLUSION: The synthesized prodrug proved to be a good antimicrobial substance due to improved lipophilicity and would be expected to be used as a suitable candidate for exploration of possible utilities in treatment of bacterial infections in forthcoming time.

Pharmacokinetics of norfloxacin after intravenous, intramuscular and subcutaneous administration to rabbits.

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross-over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap-frozen at -45°C and analysed for norfloxacin concentrations using high-performance liquid chromatography. The terminal half-life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD) 108.25 ± 12.98% and the Cmax was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD) 84.08 ± 10.36% and the Cmax was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro-organisms with MIC ≤0.14 or 0.11 µg/mL, respectively.

Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m.

BACKGROUND: This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m. METHODS AND RESULTS: The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, Ka and Cmax of norfloxacin were significantly reduced in high altitude group (p<0.05). However, the MRT, CL, t1/2 and Vd were significantly increased (p<0.05). CONCLUSIONS: These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.

The Enhancement of Nasal Drug Absorption From Powder Formulations by the Addition of Sodium Carboxymethyl Cellulose.

For nasal drug absorption, powder formulations can be expected to provide many advantages. The first aim of this study was to examine drug absorption following nasal administration of powder formulations in rats. Pharmaceutical excipients are typically added to most powder formulations. The second aim was to investigate the change in nasal drug absorption of powder formulations in the presence of sodium carboxymethyl cellulose (CMC-Na). Model drugs used were norfloxacin (NFX), warfarin (WF), and piroxicam (PXC). The absorption from bulk powders is different from that of solutions. The absorption of PXC and WF from powder formulations was enhanced compared to those of the other solutions, while that of NFX, which has a low solubility, was decreased, suggesting that the nasal absorption of many drugs, except poorly soluble drugs, is enhanced when they are administered as powder formulations. CMC-Na enhanced the absorption of NFX and PXC. The presence of CMC-Na slightly decreased the absorption of WF. In vitro transepithelial transport from the powder formulation was not affected by the presence of CMC-Na. Furthermore, the nasal retention of the powder formulation was significantly increased in the presence of CMC-Na. In conclusion, the nasal absorption of many drugs, except those that are poorly soluble, can be increased by administering them as a powder formulation and the nasal absorption of the formulation is enhanced further in the presence of CMC-Na.

Investigation and Optimization of the Effect of Polymers on Drug Release of Norfloxacin from Floating Tablets.

BACKGROUND: Norfloxacin is fluoroquinolone anti-infective used in the treatment of urinary tract infections, prostatitis, gonorrhea and genital tract infections. It has plasma half life of 3 to 4 h requiring multiple dosing in the treatment. Releaseretarding polymers can be used to modulate the drug release of norfloxacin. OBJECTIVES: The objective of this study was to investigate the effect of release-retarding polymers on the drug release of norfloxacin from floating tablets. MATERIAL AND METHODS: Norfloxacin was procured as a gift sample from Concept Pharma Ltd. Aurangabad (India) and HPMC K100M was procured as a gift sample from Colorcon Asia Pvt. Ltd., Goa (India). The tablets were prepared by direct compression method and various pharmaceutical parameters were evaluated. RESULTS: It was observed that all tablet formulations F1-F9 retained the drug release up to 12 h with good floating property but only Batch-F4 complies with the USP dissolution limits with a minimum floating lag time. The drug release kinetics were evaluated by the model-dependent (curve fitting) method using PCP Disso v3 software shows Batch-F4 shows to best fit with Peppas model for which R2 value was 0.9921 and the release exponent value was 0.6892. CONCLUSIONS: The drug release kinetics study indicates that the floating tablets release the drug by diffusion followed by erosion mechanism. Obtained in-vitro drug release data was analyzed by design expert software for drug release at first hour and at 12th h values and found that release the selected independent variables like HPMC K100M and sodium alginate concentration has a significant effect on drug release.

Variations in the fate and biological effects of sulfamethoxazole, norfloxacin and doxycycline in different vegetable-soil systems following manure application.

The fate of sulfamethoxazole (SMZ), norfloxacin (NOR) and doxycycline (DOX) and their biological effects in radish and pakchoi culture systems were investigated. DOX dissipated more rapidly than SMZ and NOR, while radish and pakchoi cultivation increased the removal of residual DOX in soils. Dissipation of NOR was accelerated in radish soils but was slowed down slightly in pakchoi soils. Vegetable cultivation exerted an insignificant effect on SMZ removal. Investigation of antibiotic bioaccumulation showed that the uptake of DOX by radish and pakchoi was undetectable, but the radish accumulated more SMZ and NOR than pakchoi. Among the three antibiotics, only SMZ use exhibited an apparent suspension of plant seed germination, up-ground plant growth and soil microbial diversity. Pakchoi responded more sensitively to SMZ than did the radish. Principal component analysis (PCA) based on MicroRESP™ indicated that the sampling time and antibiotic treatments could influence the soil microbial community. Only in the pakchoi soils did antibiotic application exert a more robust effect on the microbial community than the sampling time; SMZ treatments and DOX treatments could be clearly discriminated from the control treatments. These results are crucial for an assessment of the potential risks of antibiotics to culture system practices and suggest that good agricultural practices help to limit or even reduce antibiotic pollution.

Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass Carp.

The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or 1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real time-PCR. The concentration of NOR was determined using HPLC. The mRNA and protein expression of P-gp in the fish intestine was significantly enhanced following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and 1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower than that from NOR alone (P < 0.05), but significantly higher than that from the control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P-gp expression. In addition, pharmacokinetic assays revealed a marked increase in area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and 304.98%, respectively. In this study, we demonstrated that the transmembrane glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp, suggesting that NOR may be a direct substrate of P-gp. More importantly, we showed that CTS can inhibit P-gp expression in a dose-dependent manner and improve the relative bioavailability of NOR in this species.

Characterization and solubility study of norfloxacin-polyethylene glycol, polyvinylpyrrolidone and carbopol 974p solid dispersions.

OBJECTIVE: Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion. METHODS: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated. RESULTS: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8. CONCLUSION: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.

Comparative pharmacokinetics of norfloxacin nicotinate in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after oral administration.

Comparative pharmacokinetics of norfloxacin nicotinate (NFXNT) was investigated in common carp (Cyprinus carpio) and crucian carp (Carassius auratus) after a single oral dose of 10 mg/kg body weight (b.w.). Analyses of plasma samples were performed using ultra-performance liquid chromatography (UPLC) with fluorescence detection. After oral dose, plasma concentration-time curves of common carp and crucian carp were best described by a two-compartment open model with first-order absorption. The pharmacokinetic parameters of common carp were similar to those of crucian carp. The distribution half-life (t1/2α ), elimination half-life (t1/2ß ), peak concentration (Cmax ), time-to-peak concentration (Tmax ), and area under the concentration-time curve (AUC) of common carp were 1.58 h, 26.33 h, 6069.79 µg/L, 1.08 h, and 103072.36 h·µg/L, respectively, and those corresponding to crucian carp were 1.36 h, 26.55 h, 9586.06 µg/L, 0.84 h, and 126604.4 h·µg/L, respectively. These studies demonstrated that 10 mg NFXNT/kg body weight in common carp and crucian carp following oral dose presented good pharmacokinetic characteristics.

Investigation of ß-cyclodextrin-norfloxacin inclusion complexes. Part 2. Inclusion mode and stability studies.

INTRODUCTION: Norfloxacin (NFX) is a broad spectrum antibiotic with low solubility and permeability, which is unstable on exposure to light and humidity. OBJECTIVE: In this study, the mode of NFX inclusion into ß-cyclodextrin complexes was evaluated and a complete physical, chemical and microbiological stability study of the inclusion complexes was carried out. METHODS: Potentiometric titrations were performed to evaluate changes in the pKa of the NFX molecule due to the formation of an inclusion complex and NMR analysis demonstrated that the NFX molecule is included in the ß-cyclodextrin cavity. RESULTS: Inclusion complexes obtained by kneading followed by freeze-drying showed improved NFX stability compared with the isolated drug or the physical mixture. This method was effective in terms of protecting the drug from photodegradation and also avoiding hydrolysis. Differences between NFX and the complexes could be evidenced by thermal analysis, infrared spectroscopy and x-ray powder diffraction as well as by determining the solubility and drug content. The antimicrobial potency was also preserved on applying the promising method of kneading. CONCLUSION: The satisfactory stability indicates that the NFX/ß-cyclodextrin complexes could be useful as an alternative to the existing NFX drug formulation.

Development and validation of a rapid turbidimetric assay to determine the potency of norfloxacin in tablets

Norfloxacin is one of the first commercially available (and most widely used) fluoroquinolone antibiotics. This paper reports the development and validation of a simple, sensitive, accurate and reproducible turbidimetric assay method to quantify norfloxacin in tablets formulations in only 4 hours. The bioassay is based on the inhibitory effect of norfloxacin upon the strain ofStaphylococcus epidermidis ATCC 12228 IAL 2150 used as test microorganism. The assay was performed 3x3 parallel lines like, three tubes for each concentration of reference substance and three tubes for each sample concentration. The results were treated statistically by analysis of variance and were found to be linear (r2 = 0.9999) in the selected range of 25-100 μg mL-1; precise (intra-assay: relative standard deviation (RSD) = 1.33%; inter-assay: RSD = 0.21%), accurate (100.74%) and robust with RSD lower than 4.5%. The student's t-test showed no statistically significant difference between the proposed turbidimetric method and an HPLC method previously validated. However the turbidimetric assay can be used as a valuable alternative methodology for the routine quality control of this medicine, complementary to other physical-chemical methods.

O norfloxacino foi a primeira fluorquinolona (e mais utilizada) disponível no mercado. Este trabalho divulga um novo desenvolvimento e validação de um método turbidimétrico simples, sensível, preciso e reprodutível para a quantificação de norfloxacino em comprimidos em apenas 4 horas. O bioensaio é baseado no efeito inibitório de norfloxacino sobre a cepa Staphylococcus epidermidis ATCC 12228 IAL 2150, utilizada como micro-organismo teste. O bioensaio foi efetuado através do delineamento de linhas paralelas 3x3, em que três tubos foram utilizados para a solução padrão e três tubos para as concentrações da amostra. Os resultados foram tratados estatisticamente pela análise de variância, apresentando coeficiente de correlação linear der2 = 0,9999, na faixa de 20 a 100 μg mL-1; precisão (intra-ensaio: desvio padrão relativo (RSD) 1,33%; inter-ensaio: RSD=0,21%), exatidão (100,74%) e robustez com RSD menor que 4,5%. O teste-tmostrou não haver diferença estatisticamente significativa entre o método turbidimétrico proposto e um método por HPLC previamente validado. No entanto, o ensaio turbidimétrico pode ser utilizado como método alternativo para o controle de qualidade de rotina para este antimicrobiano, como um complemento de outros métodos físico-químicos.

Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability.

The aim of this investigation is to identify, by in silico and in vitro methods, the molecular determinants, e.g., solubility in an aqueous medium and lipophilic properties, which have an effect on the bioavailability of five selected fluoroquinolones. These properties were estimated by analysis of the electrostatic potential pattern and values of free energy of solvation as well as the partition coefficients of the studied compounds. The study is based on theoretical quantum-chemical methods and a simple experimental shake-flask technique with two immiscible phases, n-octanol and phosphate buffer. The solvation free energy values of compounds in both environments appeared to be negative. The wide range of electrostatic potential from negative to positive demonstrates the presence of dipole-dipole intermolecular interactions, while the high electron density at various sites indicates the possibility of hydrogen bond formation with solvent molecules. High partition coefficient values, obtained by summing the atomic contributions, did not take various correction factors into account and therefore were not accurate. Theoretical partition coefficient values based on more accurate algorithms, which included these correction factors (fragmental methods), yielded more accurate values. Theoretical methods are useful tools for predicting the bioavailability of fluoroquinolones.

Bioequivalence evaluation of norfloxacin tablets based on in vitro - in vivo correlation.

Present study was designed to establish in-vitro and in-vivo correlation (IVIVC) of two immediate release tablet formulations of 400mg Norfloxacin [Drug A as test and Drug B as reference]. Dissolution study was conducted in 0.1 N HCl using USP apparatus II. In-vivo evaluation was carried out in 18 healthy humans according to a single dose, two-sequence, and cross-over randomized with a wash-out period of one week. After dosing, serial blood samples were collected for a period of 10 hours. Plasma harvested from blood, was analyzed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters were determined from plasma concentrations for both the formulations. Non-significant difference was found for test/reference ratio of these parameters and the value of F was found to be 0.99 which is in good agreement with the limits given in FDA and WHO guidelines for such parameters. Difference factor (f(1)), similarity factor (f(2)) and level A IVIVC were evaluated showing that drug A is bioequivalent to drug B.

Preparation and in vitro, in vivo evaluations of norfloxacin-loaded solid lipid nanopartices for oral delivery.

This work aims to develop norfloxacin-solid lipid nanoparticles (NFX-SLN) as an oral delivery formulation. Hot homogenization and ultrasonic technique was employed to prepare NFX-SLN using stearic acid as lipid matrix and polyvinyl alcohol as surfactant. The physicochemical characteristics of SLN were investigated by optical microscope scanning electron microscopy and photon correlation spectroscopy. Antibacterial experiments of NFX-SLN were carried out by broth dilution technique. Pharmacokinetics was studied after oral administration in male Sprague-Dawley rats. The results showed that NFX-SLN was spherical and the SLN of the optimized formulation had diameters 301 ± 16.64 nm, polydispersity index 0.15 ± 0.04, zeta potential -30.8 ± 0.69 mv, loading capacity 8.58 ± 0.21% and encapsulation efficiency 92.35 ± 2.24% with good stability at 4 °C. The NFX-SLN had sustained release effect and sustained bactericidal activity. Cytotoxicity studies in cell culture demonstrated that the nanoparticles were not toxic. NFX-SLN resulted in significantly higher plasma drug concentration than native NFX. The SLN increased the relative bioavailability of NFX by 12 folds, prolonged the plasma drug level above the average minimum inhibition concentration from 14 to 168 h. These studies demonstrate that NFX-SLN could be a promising oral formulation for enhanced bioavailability and pharmacological activities.