An Improved Method for Preparation of Cefpodoxime Proxetil (original) (raw)
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Cefpodoxime Proxetil and its By-Products: A Comparative Study as Per EP-7
Cephalosporins are the highly used Broad-spectrum antibiotics, belong to β-lactam class. Cephalosporins resemble penicillin in that they have a β-lactam structure, but the five-member thiazolidine ring characteristic of the penicillin is replaced by a sixmember dihydrothiazine ring. The bactericidal action of beta lactam antibiotics is directly attributable to their ability to react with PBP’s. The research work relates to a by-products during process for the industrial manufacture of Cefpodoxime Proxetil. The drug is registered in USP and belongs to 3rd generation drug. It was discovered by Brotzu in fungus Cephalosporium Acremonium which produces a chemical which show antimicrobial activity. Abraham isolated the three fragmentation patterns of cefpodoxime proxetil. Data from this systematic study will help improve the safety and quality of cefpodoxime proxetil types of cephalosporin antibiotics cephalosporin P, cephalosporin N, cephalosporin C.7-ACA is widely used as the substrate for synthesizing cephalosporin antibiotics. Modification of the 7-ACA side-chains resulted in the development of useful antibiotic agents, and the first agent is Cephalothin (cefalotin) was launched by. Eli Lilly Company in 1964 There are many patents which gives the procedure of Synthesis of Cefpodoxime ProxetilStability of three Cefpodoxime proxetil products available in indian market at fridge temperatures (2-8 °C), room temperature (25 °C) and elevated temperature (42 °C). Flow properties, rheological and the physicochemical parameters of both powder and reconstituted powder were used to evaluate the stability of different brands of Cefpodoxime proxetil available in india. The powder of stability samples was eluted through a C18 column with formic acid-methanol-water as the mobile phase. In total, 15 impurities were characterized in commercial samples, including 7 known impurities and 8 new impurities. The structures of these unknown compounds were deduced via comparison.
Cefpodoxime Proxetil: An Update on Analytical, Clinical and Pharmacological Aspects
2015
Cefpodoxime proxetil is an orally administered broad spectrum third-generation cephalosporin. It is a pro-drug that is de-esterified in-vivo to cefpodoxime, which has potent antibacterial activity. It is generally well tolerated and demonstrates good therapeutic potential in patients with various common bacterial infections. This compound has been used most widely in the management of infections of the respiratory and urinary tracts as well as those of the skin structure, acute otitis media, pharyngitis, tonsillitis etc. The present article describes pharmacology, pharmacokinetics, clinical aspects, adverse effects and interactions of cefpodoxime proxetil. Special emphasis is also laid on the determination of cefpodoxime proxetil in pharmaceutical dosage forms and biological fluids by employing different advanced analytical methodologies.
Formulation Development and Evaluation of the Dispersible Tablet of Cefpodoxime Proxetil
In present research work, dispersible tablets of cefpodoxime proxetil were formulated using direct compression technique using various granulation techniques and different disintegrating agents by various Pharmaceutical Exicipients. Cefpodoxime proxetil is an advanced-generation, broad-spectrum cephalosporin antibiotic approved for the treatment of acute bacterial exacerbation of chronic bronchitis (AECB), group-A beta haemolytic streptococcal pharyngotonsillitis, and uncomplicated skin/skin structure infections in adult and adolescent patients. Cefpodoxime proxetil has slightly bitter taste, poor flow propertyand poor water solubility. In this research work, initially the poor flow property was improved by comparing various granulation techniques via Trial-1 wet granulation, Dry granulation Trial-2 Lactose, Micro crystalline cellulose powder (MCCP), Carboxymethylcellulose (CMC) Calcium, Sodium lauryl Sulphate (SLS), and Croscarmellose Sodium (CCS) and Polyvinylpyrrolidone (PVP) K30 and Trial-3 by Dry granulation MCCP, Maize starch and PVP K30. The optimized formulation i.e. Trial-3MCCP, Maize starch, PVP K30 was incorporated with various Disintegrnat like SSG, CCS and Crospovidone which is encoded as Trial-3A, Trial-3B and Trial-3C respectively. The prepared tablets were evaluated by various post-compession parameters. Among 3 Batches Trial-3C using Crospovidone was found optimized since it had expressed Disintegrating Timeof 20 sec and 99.98 ± 0.023 % CDR within 55min and furthermore also found better when compared with other marketed ODT of Cefpodoxime proxetil.
Cefpodoxime Proxetil: A New Stability Indicating RP-HPLC Method
ISRN Chromatography, 2013
The present work describes the development of a sensitive and economic stability indicating high performance liquid chromatographic (HPLC) method for the determination of cefpodoxime proxetil (CP) as bulk drug and as pharmaceutical formulation. Both R and S isomers of the drug were separated using Phenomenex ( mm, 5 μm particle size) ODS column with a flow rate of 1 mL min−1 and an SPD 20 A UV detector to monitor the eluate at 252 nm. The isocratic method used a mobile phase consisting of methanol and phosphate buffer of pH 4.0 in the ratio 65 : 35. The linear regression analysis data for the calibration plots showed good linear relationship with in the working concentration range of 5–100 μg mL−1. The LOD and LOQ were 53 and 160 ng mL−1, respectively. CP was subjected to stress degradation using acid, alkali, hydrogen peroxide, dry heat, wet heat, and UV light. The standard drug peaks were well resolved from the degradation products’ peaks with significantly different retention tim...
2014
A simple, precise and accurate isocratic stability–indicating RP–HPLC method was developed and validated for the simultaneous determination of Cefpodoxime Proxetil and Dicloxacillin Sodium in commercial tablets. The method has shown adequate separation for Cefpodoxime Proxetil and Dicloxacillin Sodium from their degradation products. Separation was achieved on a Waters C18 (250 mm × 4.6 mm i.d., 5 µm particle size) column using a mobile phase consisting of Acetonitrile – 20 mM Ammonium Acetate Buffer (42:58 v/v) at flow rate of 1 mL/min and UV detection at 235 nm. This drugs were subjected to hydrolysis, oxidation, photolysis and heat to apply stress conditions. The linearity was investigated in the range of 5–25 µg/mL (r 2 = 0.9993) for Cefpodoxime Proxetil and 12.5–62.5 µg/mL (r 2 = 0.9991) for Dicloxacillin Sodium. The LOD were 0.10 µg/mL and 0.68 µg/mL for Cefpodoxime Proxetil and Dicloxacillin Sodium, respectively. The LOQ were 0.33 µg/mL and 2.06 µg/mL for Cefpodoxime Proxetil...
Antimicrobial Agents and Chemotherapy, 1992
Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two diferent oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, ftidie. TWo studies involving the same 10 healthy volunteers were performd. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 t 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 ± 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 mmn for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-the curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 ± 3.9 to 8.44 ± 1.85 mg * h/liter. After famotidine, the AUC decreased to 8.36 ± 2.0 mg . h/liter. Corresponding changes were registered for the maxmum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug in serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.
Formulation and in Vitroevaluation of Floating Tablets of Cefpodoxime Proxetil
International Journal of Current Pharmaceutical Research, 2017
Objective: The objective of research work was to formulate and evaluate the floating drug delivery system containing Cefpodoxime Proxetil using polymer HPMC K4M, Guar Gum. Methods: Effervescent floating tablets containing Cefpodoxime proxetil were prepared by direct compression technique using varying concentrations of different grades of polymer. Results: Physical parameters like hardness, weight variation, thickness and friability were within pharmacopoeial limit. Percentage drug content in all floating tablet formulations was found to be 90% to 110%. The floating time was found to be more than 12 H. floating lag time was found to be 10±2.99 second. Formulation batch F8 was selected as an optimum formulation, as possessing less disintegration time, higher water absorption ratio and good content uniformity i.e. within acceptable limit.% drug release of formulation batch F8 was found to be 96.66% in 0.1 N HCL. Conclusion: The FT-IR studies of batch F8 was carried out which showed the peak values within the spectrum corresponding to the peak values of pure drug.
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Objective: A simple, direct and accurate spectrophotometric method has been developed for the determination of cefpodoxime proxetil (CEFP) in pure and pharmaceutical formulations by complex formation with bromothymol blue (BTB). Methods: The method involves the formation of yellow ion-pair complexes between BTB reagent and CEFP in chloroform. The two formed complexes ([CEFP]: [BTB] and [CEFP]: [BTB]2) have maximum absorption at λmax 422 nm. The proposed method was validated for specificity, linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ) and robustness with an average recovery of 99.0-101.4%. Results: The formed complex ([CEFP]: [BTB]2) was measured against the reagent blank prepared in the same manner. Variables were studied in order to optimize the reaction conditions. Molar absorptivity (ε) for two complexes were 8100 and 12600 L. mol-1. cm-1 , respectively. Beer's law was obeyed in the concentration range of 0.5576-55.760 μg/ml in the present of 1x10-3 mol/l of BTB with good correlation coefficient (R 2 = 0.9995). The relative standard deviation did not exceed 4.7%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.088 and 0.27 μg/ml, respectively. Conclusion: The developed method is applicable for the determination of CEFP in pure and different dosage forms with the average assay of marketed formulations 99.5 to 103.2%, and the results are in good agreement with those obtained by the RP-HPLC reference method.
Decreasing the dose frequency of cefpodoxime proxetil increases patient compliance; patients prefer to take the drug once daily. It also improves the rate of bacterial killing and hastens the cure from the indications, and therefore increases compliance. The hydrophilic matrix of HPMC controlled the cefpodoxime proxetil release effectively for 24 hours; hence, the formulation can be considered as a once-daily sustained-release tablet of cefpodoxime proxetil. The formulation showed acceptable pharmacotechnical properties and assay requirements. In vitro dissolution studies indicated a sustained-release pattern throughout 24 hours of the study that was comparable to the theoretical release profile. Drug release kinetics indicated that drug release was best explained by Higuchi’s equation, as these plots showed the highest linearity (r 2=0.9734), but a close relationship was also noted with zero-order kinetics (r 2=0.9708). Korsmeyer’s plots indicated ann value of 0.57, which was indicative of an anomalous diffusion mechanism or diffusion coupled with erosion; hence, the drug release was controlled by more than one process. Hixson-Crowell plots indicated a change in surface area and diameter of the tablets with the progressive dissolution of the matrix as a function of time.