Physical Characterization and In Vitro Evaluation of Dissolution Rate from Cefpodoxime Proxetil Loaded Self Solidifying Solid SNEDDS.

BACKGROUND: Cefpodoxime Proxetil (CPD) is a broad-spectrum cephalosporin indicated in respiratory and urinary tract infections. CPD is a BCS class IV drug with pH-dependent solubility and has poor bioavailability. This study investigated the challenges of developing ternary components based on solid SNEDDS of CPD for in vitro dissolution rate enhancement and self-solidifying behaviour. METHODS: Tween 80, Transcutol and PEG6000 were employed as surfactants, solvents and solidifiers for a base of ternary components to develop self-solidifying solid SNEDDS, respectively. Ternary phase diagrams were used to characterize solidifying behaviour of ternary components in different proportions. S-SNEDDS formulations were drawn on the solidification areas available in the phase diagram and characterized for IR, XRD, DSC and in vitro drug release in various pH media. RESULTS: Ternary components for the preparation of self-solidifying solid SNEDDS were selected based on drug solubility. FTIR and DSC characterization studies ruled out any drug interaction between CPD and components chosen to prepare S-SNEDDS. CPD was transformed from a crystalline into an amorphous state in ternary dispersions as revealed from XRD data. Optimized formulation (S-S 1) demonstrated more than 95% of drug release irrespective of the pH environments of the medium. Calculation of dissolution efficiency and similarity factors indicate that S SNEDDS resulted in a higher drug dissolution rate over binary dispersion (p<0.01). The stability studies showed that the S SNEDDS were stable in performances and CPD assay. CONCLUSION: The present investigation provides an alternative approach for enhancing the CPD dissolution rate using self-solidifying solid SNEDDS exhibited solidification behaviour at ambient temperature conditions and drug loading, which could be exploited over conventional dosage form.

Spray dried nanospheres for inclusion complexes of cefpodoxime proxetil with ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin and methyl-ß-cyclodextrin: improved dissolution and enhanced antibacterial activity.

OBJECTIVE: The aim of the current research was the development hard cellulose capsules containing cefpodoxime proxetil (CEF) (BCS-Class II) encapsulated nanospheres of inclusion complexes with ß-CD, HP-ß-CD and M-ß-CD for efficient antibacterial therapy. SIGNIFICANCE: The reason for this phenomenon is to bring an innovative approach to effective oral antimicrobial therapy with hard cellulose capsules containing spray dried nanospheres of CEF with ß-CD, HP-ß-CD and M-ß-CD by means of increased solubility, dissolution rate and improved antibacterial efficiency with lower oral dose. METHODS: Phase solubility analyses was performed to evaluate the drug/CD interaction, involving the stoichiometry and apparent stability constant. Following the preparation of inclusion complexes by spray-drying method, complexes were characterized for physical, solid-state and microbiological analyses. In vitro dissolution from hard cellulose capsules containing CEF and CEF/ß-CD, CEF/HP-ß-CD and CEF/M-ß-CD complexes were performed. RESULTS: According to AL type phase solubility curves, complexes were formulated as 1:1 molar ratio. The solubility of pure CEF was determined as 0.241 ± 0.002 mg mL-1, the solubility of inclusion complexes increased solubility from 3 to 5 times. The strong host-guest interaction was confirmed for CEF/HP-ß-CD and CEF/M-ß-CD complexes with SEM, DSC, FT-IR and 1H-NMR analyses. Inclusion complexes were more efficient on bacterial cells (2-4 fold) than pure CEF both Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Hard-cellulose capsules filled with inclusion complexes exhibited significantly faster release than unprocessed CEF. CONCLUSION: Hard-cellulose capsules containing CEF/HP-ß-CD and CEF/M-ß-CD complexes appear to be superior alternative to commercially available CEF tablets for effective antibacterial therapy.

Study of the structure and dynamics at various parts of the antibacterial drug molecule cefpodoxime proxetil.

The structure and dynamics of cefpodoxime proxetil are elucidated by measuring chemical shift anisotropy (CSA) tensor, spin-lattice relaxation time, and local correlation time at twenty-one crystallographically different 13C nuclei sites. The principal components of CSA tensor of cefpodoxime proxetil are extracted by the two-dimensional phase adjusted sinning sideband (2DPASS) cross-polarization magic angle spinning (CP-MAS) solid-state NMR experiment, and the spin-lattice relaxation time is measured by the method outlined by Torchia(T1CP). The local correlation time is calculated by bearing in mind that the spin-lattice relaxation mechanism of 13C nuclei is mainly governed by the CSA interaction and the heteronuclear dipole-dipole interaction. The aminothiazole ring, ß-lactam ring, and dihydrothiazine ring provide stability to the drug molecule and increase the affinity of the drug to penicillin-binding proteins (PBPs) receptors. The principal components of CSA parameters, spin-lattice relaxation time, and local correlation time vary substantially for carbon nuclei residing on these three rings. These signify that not only the electronic environment, but the molecular conformation, and the local dynamics are also altered within the ring. The substitution of the acyl side chain, oxime group, and the aminothiazole ring at the C7 position of the ß-lactam ring enhances the antibacterial activity and the binding affinity of the drug. A huge variation of the spin-lattice relaxation time and local correlation time is observed in those regions. The change in the electron charge distribution and nuclear spin dynamics at different parts of the drug molecule is clear by CSA and spin-lattice relaxation measurements, which will enrich the field "NMR crystallography".

Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity.

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2-8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Repurposing of cefpodoxime proxetil as potent neuroprotective agent through computational prediction and in vitro validation.

In recent reports, NR2B-NMDA receptor antagonists showed more research value because of its strong targeting ability and less side effects potential. In 2016, EVT-101 was reported to bind in an almost entirely new binding region of this target. Whether strikingly different binding modes can improve targeting and reduce side effects is worth studying. In our preliminary work, we explored the binding patterns of ifenprodil and EVT-101, found the key amino acids and summarized the pharmacophores, hoping to find such antagonists that target the two binding modes simultaneously. In this study, we developed a scalable virtual screening workflow in the FDA-approved drugs library to identify novel NR2B-NMDAR antagonists based on the combination of two pharmacophores. Cefpodoxime proxetil (5) was identified as the hit compound, and it was found for the first time that 5 might have neuroprotective activity as a NR2B-NMDAR antagonist. This result interested us to make further study, the ligand-receptor interactions modeled by molecular docking studies showed that the compound could perfectly merge both the pharmacophore characteristics of ifenprodil and EVT-101 at the binding cavity between the ATDs of GluN1 and GluN2B. The accuracy of molecular docking results and binding stability of ligand-receptor complexes were validated through 100 ns molecular dynamics simulation and binding free energy calculation. Afterwards, MTT assay (49.8%±0.1%, 5 µM) on NMDA injured SH-SY5Y cells and evidence of the effect on attenuating Ca2+ influx induced by NMDA were applied to validate the computational results, further investigation showed that 5 could suppress the NR2B upregulation induced by NMDA. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Isolation and characterization of Uropathogenic Escherichia coli (UPEC) from red panda (Ailurus fulgens).

BACKGROUND: Disease prevention and control is a significant part in the ex-situ conservation of the endangered red panda (Ailurus fulgens), being bacterial infection is one of the most important health threats to the captive population. To date, studies about the infection caused by Escherichia coli in the red panda are scarce. This study was conducted to determine the cause of death of a captive red panda through clinical symptoms, complete blood count, biochemical analysis, pathological diagnosis and bacterial whole genome sequencing. CASE PRESENTATION: The following report describes a case of a 1.5 year old captive red panda (Ailurus fulgens) that was found lethargic and anorectic. She was moved to the quarantine area for daily treatment with 50 mg of Cefpodoxime Proxetil. During the three-day treatment, she did not eat or defecate, and then died. Clinical hematology revealed the values of neutrophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were significantly higher. Histological analysis demonstrated major pathological damage in the kidneys, liver and lungs, characterized by hyperemia, parenchymal cell degeneration and necrosis and inflammatory cell infiltration which were predominantly neutrophilic. A bacterial strain confirmed as Escherichia coli was isolated post mortem. Whole genome sequencing of the E. coli showed the complete genome size was 4.99 Mbp. PapA, PapC, OmpA, OmpU and other virulence factors which specific to Uropathogenic Escherichia coli (UPEC) were found in the isolate. Among the virulence factors, P pili, type I pili and related factors of the iron uptake system were associated with nephrotoxicity. CONCLUSION: The red panda died of bacterial infection caused by an uropathogenic strain of Escherichia coli. The pathogenic mechanisms of the strain are closely related to the expression of specific virulence genes.

Taste-masking and colloidal-stable cubosomes loaded with Cefpodoxime proxetil for pediatric oral delivery.

Drug administration failure has been often witnessed in pediatric due to children's resistance to take medicines with bitter taste. Taste-masking is the key requirement among the scanty drugs available for children. Solid taste-masking systems, such as tablets and capsules, are difficult to swallow for children. Therefore, a liquid taste-masking system based on lyotropic liquid crystalline nanoparticles (LLCNs) was developed in this study. Cefpodoxime proxetil (CFP), a typically bitter drug used as antibiotic in pediatric, was selected as the model drug, and the encapsulation of CFP into the LLCNs was envisaged to improve their taste. Pluronic F127 was added to improve the colloidal stability of CFP-LLCNs. The optimized CFP-LLCNs showed the particle size of 187.29 ± 4.12 nm and the encapsulation efficiency of 85.80%. The mesophase analysis by polarized light microscopy and small angle X-ray scattering confirmed the cubic phase of CFP-LLCNs. It showed a sustained-release profile well fitted to Higuchi model, indicating that diffusion and erosion were both responsible for the CFP release. The taste-masking ability of CFP-LLCNs was confirmed by electronic tongue, compared to CFP and commercial product. The colloidal stability was verified after 3 months storage in room condition (25 ± 2 °C, 70 ± 2%RH). To sum up, the taste-masking and colloidal-stable CFP-LLCNs showed great potential for pediatric oral delivery.

Isolation and characterization of side-products formed through ∆2-isomerization in the synthesis of cefpodoxime proxetil.

In the synthesis of cephalosporin antibiotics, esterified in 4-position, the ∆2-isomerization is a well-known side reaction proceeding under basic conditions. In this work, we investigated the ∆2-isomerization of the esterified cefpodoxime proxetil. Due to the R-configuration and S-configuration of the stereogenic center in the side chain in 4-position, there are two starting materials being diastereomeric to each other. Furthermore, an additional stereogenic center is formed in the isomerization step, thus leading to four possible products. To the best of our knowledge, in this work for the first time the ∆2-isomerization of the two isolated diastereomers of AMCA proxetil, a precursor of cefpodoxime proxetil, as a starting material is reported. It has been shown, that each diastereomer only reacts to one of the two possible ∆2-diastereomers. The synthesis, isolation and characterization of (R)-diastereomers as well as (S)-diastereomers of ∆2-AMCA proxetil and cefpodoxime proxetil, respectively, are presented.

Development and validation of RP-HPLC method for simultaneous determination of cefpodoxime proxetil and H2 receptor antagonists in pharmaceutical dosage forms.

A new method on RP-HPLC is devised and validated, as per ICH guidelines, for the synchronous estimation of cefpodoxime proxetil and H2-receptor antagonits that are Cimetidine, Famotidine and Ranitidine. The method is simple, accurate, expeditious, reproducible, robust and precise. Chromatography was done on a C18 (250 x 4.6mm) column with methanol: water as mobile phae in the ratio of 70:30 (v/v), pumped at a flow rate of 1ml/min and pH was maintained using 85% ortho-phosphoric acid at 3. The λ max 240 nm was preferred for UV detection. A good linear relationship was attained, over the concentration ranges of 20-70 µg/ml and 5-30µg/ml, for cefpodoxime proxetil and H2 blockers respectively, with a correlation coefficient of R= 0.9987 to 0.9992. The method was validated and found precised (i.e. intra day and interday analysis) with RSD <2%. LOD and LOQ observations were under 0.4806 to 2.6069µg/ml which proved the method to be sensitive. The method provided satisfactory results of robustness and reproducibility, when validated and applied successfully for analysis of dosage forms.

In vitro Spectroscopic studies on drug interaction of cefpodoxime proxetil and H2 receptor blockers.

One of the relatively advance 3rd generation cephalosporins, cefpodoxime proxetil, is being used all-around. Generally, these are used for the cure of infections allied to urinary and respiratory tract. These cephalosporins have showed a remarkable in vitro activity against many strains of bacteria which are resistant to other orally used active medicinal substances. It is the first oral 3rd generation cephalosporin to be used in the cure of skin infections. The practice of H2 receptor antagonists, concerning lots of treatments recommended in patients with different types of ulcers and allergic urticarial condition, is raising hazards of unwanted secondary outcomes and drug interactions. Learning of in-vitro interaction between cefpodoxime poxetil and H2 blockers (Ranitidine, Famotidine and Cimetidine) were examined applying UV/Visible spectrophotometry and Infrared spectrometry. In the existence of H2 receptor blockers, the cefpodoxime proxetil availability was found to be decreased in vitro only under specific conditions. Furthermore, complexes of Cefpodoxime proxetil-H2 receptor antagonists were manufactured approving the interaction of these drugs. Finally, the above mentioned spectrophotometric techniques were employed to examine the complexes formed (Cefpodoxime proxetil-cimetidine, cefpodoxime proxetil-famotidine and cefpodoxime proxetil-ranitidine).

Cefpodoxime proxetil as a therapeutic option in switching therapy for infective endocarditis in children: case reports and literature review.

Infective endocarditis (IE) is uncommon in children, affecting predominantly subjects with congenital heart disease (CHD) and patients with indwelling central lines. The principles of antibiotic treatment in paediatric population are similar to those in adults. Prolonged intravenous administration of bactericidal rather than bacteriostatic agents is preferred. Outpatient intravenous therapy after initial treatment in the hospital may be considered only in selected patients. Partial oral treatment has been described in cases of left-sided, uncomplicated IE caused by common pathogens in adult patients. There are no guidelines or trials in paediatric population regarding switching therapy from intravenous to oral route. We present two cases of IE in children caused by uncommon pathogenic bacteria (Abiotrophia defectiva and Haemophilus parainfluenzae) successfully treated with oral third-generation cephalosporin - cefpodoxime proxetil after initial intravenous therapy. This paper provides observations on different therapeutic approach for IE in children as well as another potential use of cefpodoxime proxetil.

Cefpodoxime proxetil.

A comprehensive profile of cefpodoxime proxetil including the nomenclatures, formulae, elemental composition, appearance, uses, and applications. The methods which were developed for the preparation of the drug substance and their respective schemes are outlined. The physical characteristics of the drug including the ionization constant, solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal behavior, and spectroscopic studies are included. The methods which were used for the analysis of the drug substance in bulk drug and/or in pharmaceutical formulations includes the compendial, spectrophotometric, electrochemical and the chromatographic methods. The other studies which was carried out on this drug substance are including the drug stability, pharmacokinetics, bioavailability, drug evaluation, comparison and several compiled reviews. Finally, more than two hundred references are listed at the end of this profile.

Roultella ornithinolytica infection in infancy: a case of febrile urinary tract infection.

Raoultella ornithinolytica is a Gram-negative, non-motile, encapsulated, aerobic bacillus belonging to the Enterobacteriaceae family. R. ornithinolytica is a not very common, but emergent causal agent of human infection, and its expression of beta-lactamase provides resistance to commonly used antibiotics. The pathogenetic potential of R. ornithinolytica isolates in human disease has become increasingly important. Several cases of hospital-acquired infection, mostly associated with invasive procedures, or in patients with co-morbidity caused by R. ornithinolytica, have been previously reported in the adult population. In pediatric population, two cases in immunocompromised children, one case in an infant with visceral heterotaxy and one case of catheter-related bacteraemia are described. Here, we present the first case of febrile urinary tract infection due to R. ornithinolytica in an 8-month-old infant, recovered from a previous febrile UTI caused by E. coli and without co-morbidity. The empiric therapy with ceftriaxone, followed by cefpodoxime proxetil, resolved symptoms: the clinical condition of the infant improved rapidly and the treatment eradicated urine from the R. ornithinolytica infection. Since other pathogens rather than R. ornithinolytica are usually identified in children with urinary tract infections, including Escherichia coli, Proteus, Klebsiella and Pseudomonas, the identification of this microorganism in our patient's urine was also unexpected.

Development and validation of HPLC method for the determination of Cefpodoxime Proxetil in human plasma.

A new, simple, accurate, precise and specific method has been developed for the analysis of Cefpodoxime Proxetil in human plasma. The proposed method was developed and validated with the aim to be used in Bioavailability/Bioequivalence studies for quantification of drug in human plasma. The mobile phase components were acetonitrile, methanol, and water in the ratio of 20:50:30. Ortho phosphoric acid was used to adjust at pH5.0. Flow rate and wavelength were kept 1ml/min and 247nm respectively. The column was C-18 HPLC column 5um particle size, L x 1.d. 25cm x4.6mm. (Supelcosil). Retention time of Cefpodoxime Proxetil was found to be 10.967min. The developed method was validated for selectivity, recovery, accuracy, precision, repeatability, reproducibility, stability and linearity in the range of 0.195mcg/ml to 50mcg/ml. The accuracy and Precision of the proposed method were well within the predefined limits i.e. ±15% for all the calibration standards other than LLOQ (Lower Limit of Quantification) where it was well within ±20% of the nominal value. The analytical recovery was always above 89% showing satisfactory recovery. The coefficient of correlation (R2 ) was 0.999. The developed method was found suitable for the estimation of Cefpodoxime Proxetil in plasma.

Impact of different organic acids on solubility enhancement of cefpodxime proxetil immediate release tablet and its stability studies.

Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r2adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

Validated HPLC method for the pharmacokinetic study of oral extended-release cefpodoxime proxetil chitosan-alginate beads in rabbits.

The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan-alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250×4.6mm) with the mobile phase consisting of (0.02mol/l (20mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH=4.6) at a flow rate of 1.0ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R2=0.9905) in the working concentration range of 0.5-50µg/ml. The limits of detection and quantification (S/N=3) were 0.069 and 0.136µg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed.

In vitro/in vivo evaluation of HPMC/alginate based extended-release matrix tablets of cefpodoxime proxetil.

The purpose of this research was to assessment of antimicrobial activity and in vitro/in vivo evaluation of cefpodoxime proxetil extended-release (ER) tablet for once daily administration. The tablets were prepared using combination of biodegradable polysaccharides including hydroxypropyl methylcellulose and sodium alginate as matrix material to achieve pH-independent ER release. The tablets were found within the permissible limits for various physicochemical parameters. The in vitro drug release showed that the drug was released over a period of 24h in a sustained release manner. The drug release followed Higuchi kinetics as these plots showed the highest linearity (R(2)=0.9833), but a close relationship was also observed with zero-order kinetics (R(2)=0.9088) and the drug release mechanism was found to be of anomalous or non-Fickian type. Further, in vitro drug release was assessed by antimicrobial assay and it revealed that drug release through 24h periods was above the MIC. In vivo investigation in rabbits showed ER pharmacokinetic profile of cefpodoxime from the matrix tablets. A good correlation of drug absorption in vivo and drug release in vitro (R(2)=0.9785) was observed. These results suggested that the investigated CFP matrix tablets have a potential for extended-release dosage forms.

Formulation of extended release cefpodoxime proxetil chitosan-alginate beads using quality by design approach.

The purpose of this work was to develop and characterize chitosan-alginate beads for the extended delivery of cefpodoxime proxetil (CFP), to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design approach. For this, a study was performed with various formulation and process parameters to determine their impact on CQAs of beads, which were determined to be time for 80% of the drug released (T80%), particle size, and encapsulation efficiency. The beads of CFP were optimized using a three-factor, three-level Box-Behnken design. A formulation comprising of 4.38% (w/v) alginate, 1.39% (w/v) chitosan and 6.82% (w/v) calcium chloride was found to fulfill requisites of an optimum formulation. In vitro release studies showed that the drug is released from the optimized formulation over a period of 24h in a sustained release manner, primarily by non-Fickian diffusion. The optimized formulation was characterized by DSC, FTIR, XRD and SEM analysis. Antimicrobial studies revealed that the release of the drug over 24h periods was above the minimum concentration required for inhibition of microbial growth. This research highlights the level of understanding that can be accomplished through a well designed study based on the approach of QbD.

Impact of 2011 French guidelines on antibiotic prescription for acute otitis media in infants.

OBJECTIVE: In 2011, new guidelines on antibiotic prescription for acute otitis media (AOM) were published in France to decrease the use of third generation cephalosporins that promote the carriage of extended-spectrum beta-lactamase producing Escherichia coli. Our objective was to assess the impact of the 2011 French recommendations on the type of antibiotics prescribed for AOM. METHODS: Fourteen thousand six hundred and sixty-one children, 6 to 24 months of age, presenting with AOM were included in 2 studies, between November 1, 2009 and October 31, 2012. The first one was conducted with the support of 62 private practice pediatricians; the second one was conducted in 7 pediatric emergency departments. Three periods of 1 year each were defined. RESULTS: Antibiotics were prescribed in 12,471 (85.1%) of cases of AOM during the study period. Amoxicillin prescriptions was multiplied by 25, between the first year (2.6%) and the last year (66.1%). Conversely, prescriptions of cefpodoxime proxetil and amoxicillin-clavulanic acid decreased from 33.6% and 62.0% in the first year to 5.2% and 27.7% in the last year, respectively. This trend was observed in both private practices and in the pediatric emergency departments. CONCLUSION: Amoxicillin became the most frequently prescribed antibiotic for AOM in 2012, complying with the 2011 French guidelines, while the proportion of prescribed broad-spectrum antibiotics decreased. Our study highlights the importance of guidelines to decrease the prescription of broad-spectrum antibiotics, a crucial factor in the prevention of antibiotic resistance.

Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.