Investigation of factors responsible for low oral bioavailability of cefpodoxime proxetil

Kakumanu, Vasu Kumar; Arora, Vinod; Bansal, Arvind K.

doi:10.1016/j.ijpharm.2006.03.004

Cited by 33 publications

(17 citation statements)

References 11 publications

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“…9) The stability of the drug was assessed in buŠers of pH 1.2, 4.5, 5.4 and 6.8 at 37°C. These pH values represent the local environments of stomach, duodenum, jejunum and ileum, respectively.…”

Section: Proof Of Concept For Suitability and E‹ciency Of Gr Systems mentioning

confidence: 99%

“…1) However, a more recent descriptive study showed that oral bioavailability is limited because of typical eOEux of CA, which is formed in the intestinal epithelial cells by metabolism of CP. 9) However, the high solubility, chemical and enzymatic stability and absorption proˆles of CP in acidic pH values (of stomach), points to the potential of a gastroretentive (GR) dosage form in altering the absorption proˆle of CP. The objective of the present study was to evaluate the suitability and advantage of a GR dosage form of CP to improve its oral bioavailability.…”

Section: Introductionmentioning

confidence: 99%

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Gastro-retentive Dosage Form for Improving Bioavailability of Cefpodoxime Proxetil in Rats

2008

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Cefpodoxime proxetil (CP) is a prodrug with poor oral bioavailability because of its metabolism to Cefpodoxime acid (CA) in luminal contents and intestinal epithelial cells. In the present investigation, regional variability in diŠerent segments of the gastrointestinal tract vis-àa-vis solubility and metabolism were investigated, and the results indicated potential for a gastro retentive (GR) dosage form. Suitability of a GR dosage from for CP andˆnally in vivo e‹cacy were investigated. Thereafter, an eŠervescent ‰oating GR dosage form was developed for CP and evaluated in rats. The GR dosage form improved the oral bioavailability of CP signiˆcantly by about 75％, hence providing a proof-of-concept. The T max value increased to 1.43±0.24 h from 0.91±0.23 h of pure drug, while C max values of 4735±802 ng/ml and 3094±567 ng/ml were obtained for the GR dosage form and pure drug respectively.

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Section: Proof Of Concept For Suitability and E‹ciency Of Gr Systems mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gastro-retentive Dosage Form for Improving Bioavailability of Cefpodoxime Proxetil in Rats

2008

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“…5) Recently, nanosuspensions have shown promising potential in drug delivery to offer a unique solution for the poor bioavailability of poorly water-and lipid-soluble drugs. Nanosuspensions are colloidal dispersions of nano-sized drug particles stabilized by suitable stabilizers.…”

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confidence: 99%

Physicochemical and Pharmacokinetic Characterization of a Spray-Dried Cefpodoxime Proxetil Nanosuspension

Gao

Qian²,

Zhang

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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Cefpodoxime proxetil (CP) is a prodrug, broad spectrum, third generation cephalosporin ester. This prodrug ester is absorbed from the intestinal tract after oral administration and is hydrolyzed in vivo into the active cefpodoxime.1) Although CP is designed to improve the permeability and thus bioavailability of cefpodoxime, it still has only 50% oral bioavailability, when administered orally.2) The reported explanations for the low bioavailability of CP include low solubility in aqueous solution, typical gelation behavior in acidic aqueous environments and pre-absorption luminal metabolism of cefpodoxime by the action of digestive enzymes. 3,4) Metabolism of CP into cefpodoxime inside the intestinal epithelial cell and preferential efflux of cefpodoxime into lumen is also another contribution to the low bioavailability of CP. 5)Recently, nanosuspensions have shown promising potential in drug delivery to offer a unique solution for the poor bioavailability of poorly water-and lipid-soluble drugs. Nanosuspensions are colloidal dispersions of nano-sized drug particles stabilized by suitable stabilizers. Nanosuspensions are unique because of their simplicity and the advantages they confer over other formulation strategies.6) Oral nanosuspensions have been specifically used to increase the rate and extent of the absorption of poorly water-soluble drug, to enhance the onset of action, to reduce the fed/fasted ratio, and to enhance the bioavailability. In other cases, the particulate nature of nanosuspensions can be useful in the targeting of the monocyte phagocytic system, bypassing the passage of drug through epithelial cells with improved pharmacokinetic consequences.7) Nanosuspensions can also be used in controlled drug delivery systems. 8)Nanosuspension is generally prepared to be a liquid form. In order to prepare the solid dosage form for the purpose of better physical and chemical stability, spray drying is one of the commonly used techniques for solidification. However, research literature that discusses the use of spray drying for nanosuspension is limited. Recently, the spray dried nanosuspension of itraconazole was prepared.9) The emphasis was to examine the impact of various formulation and processing parameters on redispersibility of the spray dried nanoparticles and in-vitro dissolution. The in-vivo study was not performed to demonstrate the bioavailability enhancement by nanosuspension.As a solid product, solid spray-dried cefpodoxime proxetil nanosuspension (SDN) will be reconstituted in aqueous solution to form the liquid state prior to administration. It's better for SDN to regain its original state. For a heterogeneous disperse system, the rheological and thixotropic properties are important for its physical stability and clinical use. However, literature for the rheological and thixotropic properties of nanosuspensions is lacking.The main objective of the present study is to characterize the physicochemical properties of the liquid nanosuspension prepared by high pressure homogenization and SDN. I...

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“…CP exhibits pH dependent solubility behaviour, with highest solubility in acidic pH. 12 CP is used in treatment of acute otitis media respiratory tonsillitis and urinary tract infections, sexually transmitted diseases, skin infections, and pharyngitis. The bioavailability of CP is only 50% when given in conventional dosage form as it is stable in acidic pH and degrades at basic pH.…”

Section: Introductionmentioning

confidence: 99%

Formulation and Evaluation of Floating Microcapsules of Cefpodoxime Proxetil

Rao¹,

Yunusi²,

Shelar³

2014

IJPER

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Introduction: Floating drug delivery system is widely used technique to obtain higher bioavailability for drugs which have an absorption window in the stomach. Floating microcapsule is one approach to improve gastroretention for oral sustained release dosage forms. Cefpodoxime Proxetil has a biological half life of 2.5 h and is degraded at higher pH. Objective: Aim of this study was to develop floating microcapsules of Cefpodoxime Proxetil by solvent evaporation technique using Eudragit S100 as a release retarding material. Experimental: A 32 full factorial design was employed to investigate the relationship between concentration of Eudragit and stirring speed on percent release at 12 h, percent entrapment efficiency and particle size. The microcapsules were also characterized for drug content, percentage yield, floatability and surface morphology. Results: The particle size of all batches was found to be in the range of 150-290 µm. Increase in concentration of Eudragit S100 was found to increase the entrapment efficiency and mean particle size of the microcapsules. The percent release was found to be higher for microcapsules prepared at higher stirring speed which could be due to lower particle size of microcapsules and hence reduced diffusional path length. All batches of microcapsules remained buoyant for 12 h. It was observed that increasing the polymer concentration caused a decrease in the rate of drug release. The optimum formulation was subjected to pharmacokinetic studies. In vivo studies revealed a 1.6 fold increase in relative bioavailability of Cefpodoxime Proxetil as microcapsules.

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Investigation of factors responsible for low oral bioavailability of cefpodoxime proxetil

Cited by 33 publications

References 11 publications

Gastro-retentive Dosage Form for Improving Bioavailability of Cefpodoxime Proxetil in Rats

Gastro-retentive Dosage Form for Improving Bioavailability of Cefpodoxime Proxetil in Rats

Physicochemical and Pharmacokinetic Characterization of a Spray-Dried Cefpodoxime Proxetil Nanosuspension

Formulation and Evaluation of Floating Microcapsules of Cefpodoxime Proxetil

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