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The present study was designed to investigate the solubility and penetrability of norfloxacin after the topical application of developed lipid-polymer hybrid nanoparticle (LPN) formulation. The core shell of the LPNs formulation was composed of poly (lactic-co-glycolic acid) that is highly lipophilic in nature, thus control the release of drug. The developed formulations were characterised for size, shape (transmission electron microscopy [TEM], scanning electron microscopy [SEM], and atomic force microscopy), entrapment efficiency, Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Moreover, in vitro skin permeation studies were performed to determine release profile of the drug. Norfloxacin loaded nanoparticles retained there antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa. Stability study was suggested that the suitable storage condition should be at 4 ± 2 °C/60 ± 5% RH for the LPNs. Therefore, these nanoparticles showed a safe and effective long-lasting approach for long treatment of bacterial infections due to burn. more...

Objective: The aim was to optimize norfloxacin niosomes for enhanced antibacterial activity and reduced bacterial resistance., Methods: Pseudomonas aeruginosa, a biofilm forming bacterium, was used as the test organism. Different norfloxacin niosomes were evaluated in vitro and in vivo, respectively, for antibacterial activity compared with aqueous drug solution. The influence of norfloxacin niosomes on biofilm formation was investigated. The interaction of niosomes with bacterial cells was also monitored using the scanning electron microscopy (SEM)., Results: The efficacy of niosomes depended on their composition. Standard niosomes of Span 60 and cholesterol were similar to drug solution. Incorporation of Tween 80, oleic acid (OA), OA/propylene glycol or lecithin produced fluid niosomes which reduced the MIC and inhibited biofilm formation compared with drug solution. Incorporation of a positively charged agent into fluid niosomes enhanced the antibacterial activity and reduced biofilm formation significantly. SEM showed evidence of vesicle adsorption to the bacteria with possible adhesion or fusion with the cell membrane. The in vivo skin model confirmed the in vitro results with optimum niosomes being more efficient than drug solution., Conclusion: Niosomes are promising for enhanced antibacterial activity and reduced resistance to antibiotics. The later can be achieved by inhibition of biofilm formation. more...

Objectives: This study intended to describe the development of two novel, biocompatible and potential surface hydroxylated quaternary ammonium chloride based poly(propylene imine) (PPI) dendrimers for effective delivery of the drug Norfloxacin (NFN)., Methods: The synthetic pathway involved the hydroxylation and methylation of generation 2 and 3 PPI dendrimers and thus produced surface hydroxylated and internally quaternised PPI dendrimers viz., QPPI-OH (G2) and QPPI-OH (G3), respectively. The potential of these dendrimers were examined as drug carrier for NFN, by carrying out solubility, in vitro release, cytotoxicity and anti-bacterial studies., Results: It was observed that the QPPI-OH (G2)/QPPI-OH (G3) dendrimers have excellent solubilising potential/drug loading abilities of NFN in aqueous medium and can also sustain delivery of NFN. The effective complexation of NFN with QPPI-OH (G2) and QPPI-OH (G3) increased the solubility of NFN and thus elevates the NFN drug from Class 4 to Class 3 (according to BCS). These dendrimers increase the biocompatibility and increase the tolerance concentration during drug-dendrimer formulations. Anti-bacterial studies showed that the efficacy of the drug was increased in the presence of dendrimer carriers., Conclusions: These results indicate that the QPPI-OH (G2) and QPPI-OH (G3) dendrimers might be considered as potential biocompatible drug carriers of fluoroquinolines under suitable conditions. more...

Norfloxacin (Nflx), an antibiotic which is active against some intracellular bacteria, was coupled to a polymeric carrier, namely poly(L-lysine citramide) via a lysine or an ethylcarbamate spacer to obtain a macromolecular prodrug. The carrier, which derived from the two metabolites citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions. Conjugates were characterised by UV, 1H and 13C NMR and SEC. The presence of Norfloxacin and the lysine type spacer caused chain aggregation, due to a probable physical cure. The release of Norfloxacin from these prodrugs and from a prodrug where Norfloxacin is bound to the carrier backbone without spacer arm was investigated comparatively in vitro. Conjugation via a carbamate-type linkage appeared as a method to achieve the release of Norfloxacin from a PLCA-type conjugate at neutral. more...

The stability of norfloxacin as extemporaneous suspensions compounded from two brands of film-coated tablets (formulas I and II) was studied. The vehicle consisted of tragacanth, saccharin sodium, sorbitol solution, glycerin, paraben concentrate, peppermint spirit BP, purified water, and syrup USP. The final concentration of norfloxacin in the suspensions was 20 mg/ml. Formulas I and II were chemically stable for 28 days when stored in amber glass bottles at ambient temperature; however, their physical characteristics were different. more...

With the aim of promoting the targeting of macrophage mannose receptors and the internalisation of the norfloxacin antibiotic, which is active against some intracellular bacteria, a macromolecular prodrug was synthesised where the antibiotic and mannosyl moieties were coupled to a polymeric carrier, namely poly(L-lysine citramide imide). This carrier, which derived from two metabolites, citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions. Norfloxacin was coupled onto the acid groups present along the polymer chains, and conjugates were characterised by UV, TLC and SEC. The mannosyl groups selected to promote the targeting of the mannose-specific lectin present on the outer membrane of macrophages were incorporated through a biodegradable glycolic spacer arm. Two different strategies were considered to synthesise the full conjugates, namely coupling norfloxacin onto mannosylated conjugates, and coupling mannose onto PLCAI/Nflx conjugates. The second pathway led to better results regarding mannosylation. The presence of norfloxacin and mannose caused chain aggregation, especially for conjugates with a high content of mannosyl residues. The targeting ability of the prodrug was investigated using a method based on the competition between the mannosylated macromolecules and glucose oxidase, a mannosyl-bearing non-human protein. This method showed that prodrug macromolecules competed effectively with glucose oxidase and thus should be able to bring the drug up to the mannosyl receptor-bearing membranes of macrophages infected by intracellular bacteria. more...

A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the therapy of patients with Vero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive polymers, Eudragit S100 and L100. To compare the dissolution site of P-4135F coated tablets with other enteric polymer coatings, mini-tablets containing sodium fluorescein (FL) as a model drug were prepared by coating them with the three polymers. After oral administration of FL mini-tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7+/-0.2 h for Eudragit L100, 1.8+/-0.4 h for S100 and 2.0+/-0.3 h for P-4135F. Direct inspection of the dissolution process of the FL mini-tablets after oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for P-4135F, at the middle part of the ileum for Eudragit S100 and at the proximal part of the ileum for Eudragit L100. NFLX tablets with different membrane thicknesses of P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33+/-0.33 h for 56.8+/-0.5 microm membranes, 3.75+/-0.25 h for 64.6+/-0.7 microm membranes, 4.00+/-1.00 h for 70.5+/-0.5 microm membranes and 3.00+/-1.00 h for 74.9+/-0.4 microm membranes. By comparing the Ti, 4.33+/-0.33 h, obtained after oral administration of NFLX in a pressure-controlled colon delivery capsule, and the colon arrival time, 3.5+/-0.3 h, determined by a sulfasalazine test in beagle dogs. P-4135F coated NFLX tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new polymer will be useful for the delivery of NFLX to the lower part of the small intestine. more...

In a controlled, randomized, double-blind study, 100 patients (66 women, 34 men; age 18-69 years) with acute salmonellosis were treated with norfloxacin (400 mg) or placebo tablets twice daily for 10 days to compare the effects on the excretion time of salmonella bacteria. In all patients salmonellae were detected in the stools before the start of treatment. The follow-up included 6 stool cultures after the start of treatment: day 3-4, day 12-14, and 4 times during 1-6 months. At 3-4 days there were 98% non-excretors in the norfloxacin group (46/47 patients) compared to 38% (17/45) in the placebo group (p < 0.001). The cumulative 6-month elimination rate in norfloxacin patients at 3-4 days was 72%, which was significantly (p = 0.0001) greater than the 31% in the placebo patients. However, there was no significant difference in the proportion of non-excretors or the elimination rate between the 2 groups at the following visits. Only one patient had an adverse event resulting in discontinuation of the treatment. We conclude that norfloxacin treatment for 10 days decreased the excretion of salmonella bacteria during the first week, but there was no difference in excretion rates 1-6 months after treatment initiation in the treatment versus placebo group. more...

15/60 subjects from one center, who all took part in a multicenter double-blind, placebo-controlled study to evaluate the effect of norfloxacin on acute enteritis, had norfloxacin sensitive strains of Campylobacter jejuni in pre-study stool specimens. Eight of the 15 subjects received active drug. In 3 of these 8, high-level quinolone resistant Campylobacter strains of the same serotype as in pre-treatment samples were isolated 4-90 days after the initiation of treatment. more...

The in vitro activities of enoxacin, lomefloxacin, norfloxacin, ofloxacin, and pefloxacin against 274 strains of Salmonella typhi isolated from suspected typhoid fever patients (137 multi-resistant strains and 137 strains sensitive to chloramphenicol, ampicillin and/or co-trimoxazole) were determined using disk diffusion and agar dilution techniques. In vitro, enoxacin was active against all tested strains with a MIC90 and inhibition zone size against multi-resistant strains of 0.12 mg/l and 34 mm diameter, respectively. Similar results were found with the other fluoroquinolones. Enoxacin and other fluoroquinolones may be the therapy of choice in cases of typhoid fever caused by organisms resistant to the standard therapy, chloramphenicol. more...

The newer fluoro-quinolones including norfloxacin, ciprofloxacin and ofloxacin are all characterized by a good penetration into tissues and cells. In contrast to beta-lactam antibiotics, these quinolones often achieve tissue concentrations which are several times higher than concurrent serum levels. Therefore, MIC values should not be related to serum concentrations only, when possibilities for the use of quinolones in tissue infections are discussed. Following oral administration, norfloxacin and ciprofloxacin are well absorbed and the bioavailability of ofloxacin is almost 100%. Absorption is delayed but not reduced by food. Ofloxacin is mainly excreted unchanged; norfloxacin and ciprofloxacin are metabolized to some extent, but most metabolites are biologically active. Half-lives of the drugs are 3-6 hours and they may therefore be administrated twice daily. These quinolones are excreted by glomerular filtration and tubular secretion but also via faeces. Dose reduction is needed only in patients with severe reduction of kidney function. It has been suggested that when renal function is reduced an increased transintestinal passage of the quinolones may result. In the intestines the quinolones seem to be bound to faeces; anaerobes are mainly unaffected by these antibiotics. more...

The influence of faeces on the activity of 9 antibiotics currently used for selective decontamination of the digestive tract was studied. These in vitro findings showed that the antimicrobial activity is differently affected by the presence and concentration of faeces. Great differences in loss of activity were observed on different microorganisms. Decontaminating drugs which were found to be minimally inactivated in vitro by the presence of faeces are proven to be superior in clinical studies too. more...

As part of a multicenter randomized trial of the treatment of complicated urinary infections in hospitalized patients, we treated 35 patients of whom 28 were evaluable (16 patients given parenteral therapy and 12 norfloxacin). The distribution of pathogens was similar in both groups as was the elimination of the organisms (12/12 norfloxacin and 14/16 parenteral therapy). The only complication of norfloxacin therapy was an episode of anxiety in a patient with obstructive lung disease who had experienced anxiety and difficulty with a variety of other medications. The largest difference between the parenteral and norfloxacin treated groups was in the ease of therapy and in cost, which for the former was a total of $5 091, i.e. $318 per patient and $30.1/day, exclusive of administration costs. The parenteral administration costs averaged $45/day. Analogous costs for norfloxacin were estimated at $3.00/day per patient and administration costs for 2 tablets norfloxacin/day were calculated at $7.5. The variety of drugs used in the parenteral arm included a nephrotoxic aminoglycosides in half the cases and a wide variety of beta-lactams as well as vancomycin. Thus, for simplicity of therapy as well as cost norfloxacin was judged superior to parenteral therapy of hospitalized patients with mild or moderately severe urinary tract infections including patients with underlying urinary tract abnormalities and prior to long term foley catheter use. An additional 15 cases were treated in an open trial or on a compassionate use basis. All but one patient, who was noncompliant, responded, including, several with chronic relapsing infections with antibody coated bacteria in the urine. Three such patients who were followed for 3-6 months maintained urine free of bacteria. more...

Norfloxacin is a quinolone derivative with demonstrated activity against Neisseria gonorrhoeae. The MIC90 against penicillinase- and non-penicillinase producing N. gonorrhoeae is 0.06 mg/l and 0.015 mg/l respectively. The drug is rapidly absorbed with a single oral dose of 800 mg producing peak serum levels of 2.45 mg/l. In this open, uncontrolled study, 70 patients with laboratory confirmed, uncomplicated infections with N. gonorrhoeae were entered to determine the efficacy and safety of a single oral dose of norfloxacin 800 mg. Thirty-one males and 27 females were evaluated for efficacy with 34 males and 25 females evaluated for safety. Norfloxacin cured all 31 urethral and two pharyngeal infections in men. All 25 females with endocervical infections and six with rectal involvement were also cured. The single treatment failure occurred in a woman who had persistent pharyngeal infection. All isolates of N. gonorrhoeae were inhibited by 0.05 mg/l of norfloxacin. The incidence of adverse effects was 23.7% but all were mild, required no specific therapy and cleared without sequelae. In this study, norfloxacin proved to be an effective agent in the therapy of uncomplicated gonococcal infection in males and females. It has previously been proven to be useful in the therapy of gonococcal infections due to penicillinase-producing N. gonorrhoeae and the value of this drug as a first line choice in the treatment of gonococcal infections is discussed. more...

Forty-one men with a clinically and bacteriologically verified diagnosis of chancroid were given a single dose of 800 mg of norfloxacin and were examined clinically and bacteriologically four, seven and 14 days after treatment. Five patients were excluded from evaluation of efficacy due to concomitant infections or incomplete follow-up. Of the remaining 36 patients, 34 were cured and culture negative at follow-up controls. Another 15 men with culture-negative ulcers treated with 800 mg of norfloxacin as a single dose, were all cured clinically. The high cure rate and the good tolerability make norfloxacin a convenient and cheap alternative to intramuscular single dose therapy of chancroid. more...

Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergoing intensive chemotherapy-induced bone marrow aplasia, and often arise from the gastrointestinal (GI) tract. The value of oral prophylactic norfloxacin (400 mg every 12 hours) in preventing bacterial infections was determined for 68 adults with acute leukemia by a prospective, randomized, double-blind, placebo-controlled trial. The efficacy of norfloxacin administered prophylactically throughout the course of intensive therapy and deep (less than 100 mm/3), prolonged (median 32 day) granulocytopenia against infections arising from the GI tract was demonstrated by its impact on the clinical manifestations of infection, microbiologically documented gram negative bacterial infections, overall antibiotic management, and GI colonization. Although there was no difference with respect to survival, norfloxacin decreased overall morbidity associated with gram-negative infections, was well tolerated, did not impinge on systemic antibacterial or antitumor therapy, and did not predispose to the development of bacteria resistant either to itself or to multiple other antibiotics. The advantages of norfloxacin relative to other oral agents used for GI prophylaxis and the potential beneficial effects of norfloxacin or overall medical cost are discussed. Oral norfloxacin achieves the goals of GI prophylaxis by effectively suppressing early infection arising from the GI tract and inhibiting GI colonization by multiply resistant pathogens that could give rise to late-onset infections during profound chemotherapy-induced bone marrow aplasia. more...

The therapeutic efficacy and safety of norfloxacin 400 mg twice daily for 3 or 7 days was compared in a double-blind randomized multiclinic study including 485 female general practice patients with uncomplicated symptomatic lower urinary tract infections. 373 patients were considered valid for efficacy, 193 in the 3-day treatment group and 180 in the 7-day treatment group. The short-term efficacy (elimination of significant bacteriuria 3-13 days post-treatment) was 93.8% and 96.6% in the 3 and 7-day treatment groups, respectively, and the accumulated efficacy (elimination of significant bacteriuria 3 days post-treatment up until 45 days after the first dose) 81.3% and 91.7%, respectively (p less than 0.004). The median time to disappearance of symptoms was 3 days in both groups. Norfloxacin was well tolerated in both treatment groups. more...

The bacteriological and clinical efficacy of norfloxacin 400 mg b.i.d. was studied in an open, non-comparative trial. Twenty-seven patients with clinical symptoms of typhoid fever were included and assigned to treatment for 14 days. Salmonella typhi was found in stools and/or blood cultures from 12 patients. Subsequent cultures from ten of these patients were negative during treatment and in the follow-up period. Two patients remained positive in stool cultures. Body temperature normalized within one week in 11 of the 12 evaluable patients. In conclusion, these results indicate the potential clinical value of norfloxacin for treatment of typhoid fever. Further controlled and comparative studies are needed. more...