Comparative Quality Evaluation of Selected Brands of Cefuroxime Axetil Tablets Marketed in the Greater Accra Region of Ghana.

The ever-growing commercialization of poor-quality and substandard medicines, especially anti-infectives characterized by inadequate postmarket surveillance by stakeholders remains a major global health challenge, particularly in developing countries, where antibiotic drug resistance and its repercussions on human health remain dominant. This research sought to evaluate the pharmaceutical quality of six randomly selected brands of cefuroxime axetil tablets (250 mg) marketed in the Greater Accra region of Ghana. The selected brands were coded and subjected to both compendial and noncompendial tests. Statistical analysis and model-independent parameter (similarity factor, f2) were employed in analyzing the dissolution profiles of all the brands. All brands including the reference brand conformed to the pharmacopeial specifications for both compendial and noncompendial tests, indicating that they were of good quality. However, there were significant variations (p < 0.05) in the disintegration time amongst the various brands. All the brands had ƒ2 values > 50 indicating similarity of their drug release profiles with the innovator. Hence, all the sampled cefuroxime axetil brands can be considered as pharmaceutical equivalents to the innovator drug. These brands can, therefore, be used as a substitute for the innovator drug by physicians to patients in cases of unaffordability or unavailability of the innovator brand.

Molecular Structure of Cefuroxime Axetil Complexes with α-, ß-, γ-, and 2-Hydroxypropyl-ß-Cyclodextrins: Molecular Simulations and Raman Spectroscopic and Imaging Studies.

The formation of cefuroxime axetil+cyclodextrin (CA+CD) complexes increases the aqueous solubility of CA, improves its physico-chemical properties, and facilitates a biomembrane-mediated drug delivery process. In CD-based tablet formulations, it is crucial to investigate the molecular details of complexes in final pharmaceutical preparation. In this study, Raman spectroscopy and mapping were applied for the detection and identification of chemical groups involved in α-, ß-, γ-, and 2-hydroxypropyl-ß-CD (2-HP- ß-CD)+CA complexation process. The experimental studies have been complemented by molecular dynamics-based investigations, providing additional molecular details of CA+CD interactions. It has been demonstrated that CA forms the guest-host type inclusion complexes with all studied CDs; however, the nature of the interactions is slightly different. It seems that both α- and ß-CD interact with furanyl and methoxy moieties of CA, γ-CD forms a more diverse pattern of interactions with CA, which are not observed in other CDs, whereas 2HP-ß-CD binds CA with the contribution of hydrogen bonding. Apart from supporting this interpretation of the experimental data, molecular dynamics simulations allowed for ordering the CA+CD binding affinities. The obtained results proved that the molecular details of the host-guest complexation can be successfully predicted from the combination of Raman spectroscopy and molecular modeling.

Effect of food on the pharmacokinetics of oral cefuroxime axetil in dogs.

Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20 mg/kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were withdrawn at predetermined times over a 12-hr period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (Cmax ), and area under the concentration-time curve (AUC) of cefuroxime axetil were significantly enhanced (p < .05) by the concomitant ingestion of food (32.97 ± 13.47-14.08 ± 7.79%, 6.30 ± 2.62-2.74 ± 0.66 µg/ml, and 15.75 ± 3.98-7.82 ± 2.76 µg.hr/ml for F, Cmax, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T½(a) ) and time to peak concentration (Tmax ) (0.55 ± 0.27-1.15 ± 0.19 hr and 1.21 ± 0.22-1.70 ± 0.30 for T½(a) and Tmax in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T > MIC (≤1 µg/ml) was <2 hr in fasted and ≈4 hr in fed animals, and for cefuroxime axetil suspension, T > MIC (≤1 µg/ml) was ≈5 hr and for T >MIC (≤4 µg/ml) was ≈2.5 hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs.

Co-processing of cefuroxime axetil by spray drying technique for improving compressibility and flow property.

The aim of the present investigation was to improve the compressibility and flow property of cefuroxime axetil by co-processing it with mannitol and chitosan chlorhydrate using spray drying method. 32 full factorial design, having inlet air temperature and mannitol: chitosan chlorhydrate ratio as independent variables was used for the optimization. Statistical analysis of obtained results revealed that both independent variables had significant effect on response variables (p value < .05). Evaluation of dependent variables suggested, excellent to good flow properties (angle of repose, Carr's index, and Hausner's ratio) for all prepared batches. Desirability function was used for the selection of the optimized batch which was evaluated for Kawakita's equation, Heckel's plot to assess compression behavior of co-processed product under applied pressure. Result of this analysis revealed that the optimized batch product had better compressibility than physical mixture. The tablets prepared by directly compressing spray-dried product, exhibited excellent tensile strength acceptable friability (<1%) and similar release profile when compared with marketed formulation (Similarity factor 89.24 and dissimilarity factor 1.79). So the results of the present investigation concluded that cefuroxime axetil was successfully co-processed with above mentioned excipients by using spray drying method to make it directly compressible.

Surface Dissolution UV Imaging for Investigation of Dissolution of Poorly Soluble Drugs and Their Amorphous Formulation.

The aim of this study is to investigate the dissolution properties of poorly soluble drugs from their pure form and their amorphous formulation under physiological relevant conditions for oral administration based on surface dissolution ultraviolet (UV) imaging. Dissolution of two poorly soluble drugs (cefuroxime axetil and itraconazole) and their amorphous formulations (Zinnat® and Sporanox®) was studied with the Sirius Surface Dissolution Imager (SDI). Media simulating the fasted state conditions (compendial and biorelevant) with sequential media/flow rate change were used. The dissolution mechanism of cefuroxime axetil in simulated gastric fluid (SGF), fasted state simulated gastric fluid (FaSSGF) and simulated intestinal fluid (SIF) is predominantly swelling as opposed to the convective flow in fasted state simulated intestinal fluid (FaSSIF-V1), attributed to the effect of mixed micelles. For the itraconazole compact in biorelevant media, a clear upward diffusion of the dissolved itraconazole into the bulk buffer solution is observed. Dissolution of itraconazole from the Sporanox® compact is affected by the polyethylene glycol (PEG) gelling layer and hydroxypropyl methylcellulose (HPMC) matrix, and a steady diffusional dissolution pattern is revealed. A visual representation and a quantitative assessment of dissolution properties of poorly soluble compounds and their amorphous formulation can be obtained with the use of surface dissolution imaging under in vivo relevant conditions.

Experimental Determination and Theoretical Calculation of the Eutectic Composition of Cefuroxime Axetil Diastereomers.

Cefuroxime axetil (CFA), an ester prodrug of cefuroxime exists as a pair of diastereoemers, namely isomer A and isomer B. To enable phase diagram construction, crystallization of the diastereomers of CFA from the commercially available amorphous drug substance was carried out. Isomer A was separated with a purity approaching 100% whereas the maximum purity of isomer B was 85% as confirmed by solution state proton NMR spectroscopy. The crystalline forms of isomer A and isomer B were confirmed as forms AI and BI, respectively, based on differential scanning calorimetry (DSC) analysis and powder X-ray diffraction. DSC analysis was used to observe the melting behavior of different diastereomer mixture compositions. The binary solid-liquid phase diagram for mixture compositions ranging from 0 to 85% w/w isomer B indicated the formation of a eutectic mixture having a melting temperature of 124.7 ± 0.4°C and a composition of 75% w/w (+/-5% wt.) isomer B. The eutectic composition was calculated using an index based on the van't Hoff equation for melting point depression and was found to be 75% isomer B and 25% isomer A. As CFA is present in commercial preparations as a mixture of diastereomers, the formation of a eutectic mixture between the diastereomers may impact the solubility and stability of the commercial product. Eutectic formation can be explained on the basis of the chemical similarity of diastereomers that favor miscibility in the liquid state.

Regional features of the microbial landscape of urine and comparative evaluation of antimicrobial therapy in children with cystitis.

INTRODUCTION: Growing resistance of pathogens to antibiotics, including cross-resistance to other antimicrobial classes that are used in the treatment of recurrent infections of the lower urinary system in children demands constant control of issues of regional antibiotic resistance. In the present days, in the empirical treatment of such patients physicians still choose medications with preserved activity in relation to E. coli. The aim of our study was to investigate the regional features of microbial landscape of urine in children with cystitis and study the efficacy of 7-day administration of Furamag medicinal drug for the treatment of recurrent episodes of this disease in children. MATERIAL AND METHODS: 65 children aged 5 to 16 years underwent clinical and laboratory examinations. The patients in Group I (33 children) received Furamag as an antimicrobial therapy; the comparison group consisted of patients (32 children) who received cefuroxime axetil. The both therapies course duration was 7 days. RESULTS: Bacteriological examination results were indicative of prevalence of gram-negative opportunistic microflora; in particular, E. coli prevailed in the structure of isolated causative agents (61.9%). Analysis of detected pathogens susceptibility to antimicrobial agents showed a high level of E.coli resistance to ampicillin, amoxicillin/clavulanate and gentamicin (in 97.4% of cases), and in 50% of cases the E.coli were resistant to cefotaxime, ceftriaxone and cefuroxime. High rates of resistance of Enterococcus spp. (100%) and Enterobacter spp. (96.7%) to cefuroxime, cefotaxime and ceftriaxone were recorded. Furamag demonstrated significantly higher bacteriological efficacy vs. cefuroxime axetil as for eradication of the most clinically significant causative agents of cystitis identified in the Poltava region (93.9% and 68.8%, respectively, p <0.05). During the follow-up study, anti-relapse efficacy of Furamag appeared to be 1.5 times higher as compared to the reference drug in the children examined (p <0.05).

Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review.

IMPORTANCE: Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections. OBJECTIVE: To provide an update on diagnosis, treatment, and prevention of tick-borne infections. EVIDENCE REVIEW: Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015. FINDINGS: The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment. CONCLUSIONS AND RELEVANCE: Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription of a 14-day course of oral doxycycline for early neurologic Lyme disease in ambulatory patients. The duration of antimicrobial therapy for babesiosis in severely immunocompromised patients should be extended to 6 weeks or longer.

Uveitis attack and drug reaction due to cefuroxime axetil.

Antibiotics are natural or synthetic substances that are used to control bacterial infections because antibiotics are by definition only effective against bacteria. A 30-year-old female came to our emergency clinic complaining rubor in both eyes, especially in the left eye, with swelling, rubor and pain in ears, and eruption in lips extremities. In her anamnesis, it has been determined that she did not have any medical disease that requires regular utilization of drugs. After the patient received cefuroxime axetil for acute tonsillitis, she observed eruptions in lip extremities on the 3rd day, but she did not care about it. On the 5th day, rubor in both eyes and, especially in the left eye, have been developed, and complaints such as unable to look toward light and pain have started together with swelling, rubor, and pain in both ears. She came to our clinic because she was very much worried about the situation. In this study, we aimed to discuss a drug reaction characterized by face and ear skin observations, due to uveitis after the use of antibiotics including cefuroxime axetil for acute tonsillitis.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

STUDIES OF THE CRYSTALLINE FORM OF CEFUROXIME AXETIL: IMPLICATIONS FOR ITS COMPATIBILITY WITH EXCIPIENTS.

Amorphous and crystalline forms of cefuroxime axetil were identified and characterized using DSC, XRPD, SEM, FT-IR and Raman spectroscopy. Based on the results of chromatographic studies, changes in the kinetic mechanism and rate of degradation of the crystalline form of cefuroxime axetil in binary systems with excipients were also evaluated. The findings suggest that the mechanism of degradation of cefuroxime axetil in such systems depends on two factors: the applied excipient and storage conditions. Cefuroxime axetil in combination with magnesium stearate, croscarmellose sodium and crospovidone, microcrystalline cellulose, aerosil is decomposed according to the first-order reaction model in dry air as well as at an increased relative air humidity, which may be associated with non-catalytic interactions between the active pharmaceutical ingredient and the excipients. However, in the presence of mannitol, under elevated humidity conditions (RH - 76%), the degradation of cefuroxime axetil follows the autocatalytic model. According to ESP maps, computed binding energies and HOMO - LUMO gaps, differences of degradation curves between cefuroxime axetil - mannitol and other investigated systems were explained. This study of the polymorphic transformation of the crystalline form of cefuroxime axetil and its binary systems with excipients after exposure to increased temperature and humidity indicated a conversion towards the amorphous form or the coexistence of both forms.

Application of vibrational spectroscopy supported by theoretical calculations in identification of amorphous and crystalline forms of cefuroxime axetil.

FT-IR and Raman scattering spectra of cefuroxime axetil were proposed for identification studies of its crystalline and amorphous forms. An analysis of experimental spectra was supported by quantum-chemical calculations performed with the use of B3LYP functional and 6-31G(d,p) as a basis set. The geometric structure of a cefuroxime axetil molecule, HOMO and LUMO orbitals, and molecular electrostatic potential were also determined by using DFT (density functional theory). The benefits of applying FT-IR and Raman scattering spectroscopy for characterization of drug subjected to degradation were discussed.

Removal of amoxicillin and cefuroxime axetil by advanced membranes technology, activated carbon and micelle-clay complex.

Two antibacterials, amoxicillin trihydrate and cefuroxime axetil spiked into wastewater were completely removed by sequential wastewater treatment plant's membranes, which included activated sludge, ultrafiltration (hollow fibre and spiral wound membranes with 100 and 20 kDa cut-offs), activated carbon column and reverse osmosis. Adsorption isotherms in synthetic water which employed activated carbon and micelle-clay complex (octadecyltrimethylammonium-montmorillonite) as adsorbents fitted the Langmuir equation. Qmax of 100 and 90.9 mg g(-1), and K values of 0.158 and 0.229 L mg(-1) were obtained for amoxicillin trihydrate using activated carbon and micelle-clay complex, respectively. Filtration of antibacterials in the ppm range, which yielded variable degrees of removal depending on the volumes passed and flow rates, was simulated and capacities for the ppb range were estimated. Stability study in pure water and wastewater revealed that amoxicillin was totally stable for one month when kept at 37°C, whereas cefuroxime axetil underwent slow hydrolysis to cefuroxime.

Determination of cefuroxime lysine in rat brain microdialysates by ultra-fast liquid chromatography with UV and tandem mass spectrometry: application to an acute toxicokinetic study.

Cefuroxime lysine is a new second-generation cephalosporins, which can penetrate the blood-brain barrier to cure the meningitis. In order to investigate its acute toxicokinetic study after intraperitoneal injection of 675 mg/kg cefuroxime lysine, a sensitive and clean ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime lysine in microdialysate samples was developed and validated, which was compared with UFLC-UV as a reference method. Chromatographic separation was performed on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm), with an isocratic elution of 0.1% formic acid in acetonitrile-0.1% formic acid in water (45:55, v/v) for LC-MS and acetonitrile-20 mm potassium dihydrogen phosphate (pH 3.0,20:80, v/v) for LC-UV. The lower limit of detection was 0.01 µg/mL for LC-MS and 0.1 µg/mL for LC-UV method, with the same corresponding linearity range of 0.1-50 µg/mL. The intra- and inter-day precisions (relative standard deviation) for both methods were from 1.1 to 8.9%, while the accuracy was all within ±10.9%. The results of both methods were finally compared using paired t-test; the results indicated that the concentrations measured by the two methods correlated significantly (p < 0.05), which suggested that the two methods based on LC-MS and LC-UV were suitable for the acute toxicokinetic study.

Differentiating amorphous mixtures of cefuroxime axetil and copovidone by X-ray diffraction and differential scanning calorimetry.

The amorphous, molecular solid dispersion of cefuroxime axetil and copovidone with the mass ratio 71/29 is compared to its pure components in the amorphous state and to an amorphous mechanical mixture with the same mass ratio. Calorimetric studies demonstrate that all these materials are vitreous. By using X-ray diffraction profiles, a clear difference can be observed between the local order of the solid dispersion and that of the mechanical mixture. More generally, it is shown how the presence or absence of additivity in the diffraction data can be used to distinguish between different amorphous mixtures.

In vitro/in vivo comparison of cefuroxime release from poly(ε-caprolactone)-calcium sulfate implants for osteomyelitis treatment.

This study aimed to investigate the release of cefuroxime axetil (CF) and calcium from poly(ε-caprolactone) (PCL)-calcium sulfate (CaS) implants (PCL:CaS 2:1-10% CF; PCL:CaS 2:1-20% CF; PCL:CaS 1:1-10% CF) for treating infectious bone diseases. Bioactivity, crystallinity and strength, and release profiles under standard and pressurized release conditions were studied. PCL:CaS 2:1-20% CF had slower release than 10% loading. These groups had no significant change in CF and Ca release in response to pressure. The PCL:CaS 1:1 group had the slowest release despite having higher CaS, probably due to more compaction of discs. In contrast, pressure caused significant differentiation of CF and Ca(2+) release. The presence of CaS enhanced mechanical properties and bioactivity of discs. SEM and XPS results showed calcium-phosphate containing accumulations on surfaces upon SBF incubation. CF-loaded implants were applied in a rabbit osteomyelitis model. In vivo CF release was enhanced with increased CaS proportions, suggesting that in vivo release conditions are closer to pressurized in vitro conditions. In the control group, there was still some inflammation in the bone and no complete coverage with bone was achieved in the defect site. Discs provided a suitable surface for regeneration of bone. However, bone formation in the PCL:CaS 1:1 disc implanted group was more complete and regular than in the 2:1 group.

Development of gastroretentive drug delivery system for cefuroxime axetil: in vitro and in vivo evaluation in human volunteers.

The objective of this investigation was to develop the cefuroxime axetil sustained-release floating tablets to prolong the gastric residence time and compare their pharmacokinetic behavior with marketed conventional tablets (Zocef). The floating tablets were developed using polymers like HPMC K4M and HPMC K100M alone, and polymer combination of HPMC K4M and Polyox WSR 303 by effervescent technique. Tablets were prepared by slugging method and evaluated for their physical characteristics, in vitro drug release, and buoyancy lag time. The best formulation (F10) was selected based on in vitro characteristics and used in vivo radiographic and bioavailability studies in healthy human volunteers. All the formulations could sustain drug release for 12 h. The dissolution profiles were subjected to various kinetic release models and it was found that the mechanism of drug release followed Peppas model. The in vivo radiographic studies revealed that the tablets remained in stomach for 225 ± 30 min. Based on in vivo performance, the developed floating tablets showed superior bioavailability than Zocef tablet. Based on in vivo performance significant difference was observed between Cmax, tmax, t1/2, AUC0-∞, and mean residence time of test and reference (p<0.05). The increase in relative bioavailability of test was 1.61 fold when compared to reference.

Bioequivalence and population pharmacokinetic modeling of two forms of antibiotic, cefuroxime lysine and cefuroxime sodium, after intravenous infusion in beagle dogs.

To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20-80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42), with a significant difference between males and females. The estimates of population pharmacokinetic of CL, V(1), Q(2), V(2), Q(3), V(3) were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium.

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats.

AIM: To compare the pharmacokinetic parameters of cefuroxime lysine, a new second-generation of cephalosporin antibiotics, after intravenous (IV), intraperitoneal (IP), or intramuscular (IM) administration. METHODS: Twelve male and 12 virgin female Sprague-Dawley rats, weighing from 200 to 250 g, were divided into three groups (n=4 for each gender in each group). The rats were administered a single dose (67.5 mg/kg) of cefuroxime lysine via IV bolus or IP or IM injection. Blood samples were collected and analyzed with a validated UFLC-MS/MS method. The concentration-time data were then calculated by compartmental and non-compartmental pharmacokinetic methods using DAS software. RESULTS: After IV, IP or IM administration, the plasma cefuroxime lysine disposition was best described by a tri-compartmental, bi-compartmental or mono-compartmental open model, respectively, with first-order elimination. The plasma concentration profiles were similar through the 3 administration routes. The distribution process was rapid after IV administration [t(1/2(d)), 0.10 ± 0.11 h vs 1.36 ± 0.65 and 1.25 ± 1.01 h]. The AUMC(0-∞) is markedly larger, and mean residence time (MRT) is greatly longer after IP administration than that in IV, or IM routes (AUMC(0-∞): 55.33 ± 20.34 vs 16.84 ± 4.85 and 36.17 ± 13.24 mg·h(2)/L; MRT: 0.93 ± 0.10 h vs 0.37 ± 0.07 h and 0.65 ± 0.05 h). The C(max) after IM injection was significantly higher than that in IP injection (73.51 ± 12.46 vs 49.09 ± 7.06 mg/L). The AUC(0-∞) in male rats were significantly higher than that in female rats after IM administration (66.38 ± 16.5 vs 44.23 ± 6.37 mg·h/L). There was no significantly sex-related difference in other pharmacokinetic parameters of cefuroxime lysine between male and female rats. CONCLUSION: Cefuroxime lysine shows quick absorption after IV injection, a long retension after IP injection, and a high C(max) after IM injection. After IM administration the AUC(0-∞) in male rats was significantly larger than that in female rats.

Chitosan-based intragastric delivery of cefuroxime axetil: development and in-vitro evaluation of mucoadhesive approach.

To have advantages of reduced dosing frequency, improved bioavailability and effective delivery system of Cefuroxime Axetil, a Chitosan based intragastric sustained release microbead formulation of Cefuroxime Axetil was developed. The drug delivery system was prepared by ionotropic gelation of Chitosan in presence of sodium tripolyphosphate as polyanion and optimized by box-behnken experimental design. Response surface methodology was applied to evaluate various vitro characteristics of prepared mucoadhesive microbeads. Multiple independent variables were optimized to achieve responses of interest, thereby to get the desired sustained release profile of Cefuroxime Axetil in gastric environment.