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Enhancement of Bioavailability of Cefpodoxime Proxetil Using Different Polymeric Microparticles

AAPS PharmSciTech volume 11, pages 1368–1375 (2010)Cite this article

Abstract

Poorly water-soluble drugs such as cefpodoxime proxetil (400 μg/ml) offer a challenging problem in drug formulation as poor solubility is generally associated with poor dissolution characteristics and thus poor oral bioavailability. According to these characteristics, preparation of cefpodoxime proxetil microparticle has been achieved using high-speed homogenization. Polymers (methylcellulose, sodium alginate, and chitosan) were precipitated on the surface of cefpodoxime proxetil using sodium citrate and calcium chloride as salting-out agents. The pure drug and the prepared microparticles with different concentrations of polymer (0.05–1.0%) were characterized in terms of solubility, drug content, particle size, thermal behavior (differential scanning calorimeter), surface morphology (scanning electron microscopy), in vitro drug release, and stability studies. The in vivo performance was assessed by pharmacokinetic study. The dissolution studies demonstrate a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of cefpodoxime proxetil from optimized microparticle was attributed to the wetting effect of polymers, altered surface morphology, and micronization of drug particles. The optimized microparticles exhibited excellent stability on storage at accelerated condition. The in vivo studies revealed that the optimized formulations provided improved pharmacokinetic parameter in rats as compared with pure drug. The particle size of drug was drastically reduced during formulation process of microparticles.

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References

  1. Prajapati BG, Patel MM. Conventional and alternative pharmaceutical methods to improve oral bioavailability of lipophilic drugs. Asian J Pharm. 2007;1:1–8.

    Google Scholar 

  2. Rawlinson CF, Adrian C, Williams AC, Timmins P, Grimsey I. Polymermediated disruption of drug crystallinity. Int J Pharm. 2007;336:42–8.

    CAS  Article  PubMed  Google Scholar 

  3. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20.

    CAS  Article  PubMed  Google Scholar 

  4. Sugimoto M, Okagaki T, Narisawa S, Koida Y, Nakajima K. Improvement of dissolution characteristics and bioavailability of poorly water-soluble drugs by novel cogrinding method using water-soluble polymer. Int J Pharm. 1998;160:11–9.

    CAS  Article  Google Scholar 

  5. Kakumanu VK, Arora V, Bansal A. Development and validation of isomer specific RP-HPLC method for quantification of cefpodoxime proxetil. J Chromatogr B. 2006;835:16–20.

    CAS  Article  Google Scholar 

  6. Kakumanu VK, Arora V, Bansal AK. Investigation of factors responsible for low oral bioavailability of cefpodoxime proxetil. Int J Pharm. 2006;317:155–60.

    CAS  Article  PubMed  Google Scholar 

  7. Kakumanu VK, Arora V, Bansal AK. Investigation of physicochemical and biological differences of cefpodoxime proxetil enantiomers. Eur J Pharm Biopharm. 2006;64:255–9.

    CAS  Article  PubMed  Google Scholar 

  8. Manciet SC, Huneau JF, Decroix MO, Tomb D, Farinotti R, Chaumeil JC. Cefpodoxime proxetil esterase activity in rabbit small intestine: a role in the partial cefpodoxime absorption. Int J Pharm. 1997;149:241–9.

    Article  Google Scholar 

  9. Schellens JHM, Malingre MM, Kruijtzer CMF, Bardelmeijer HA, Tellingen OV, Schinkel HA, et al. Modulation of oral bioavailability of anticancer drugs: from mouse to man. Eur J Pharm Sci. 2000;12:103–10.

    CAS  Article  PubMed  Google Scholar 

  10. Rasenack N, Müller HH. Int. Microcrystals for dissolution rate enhancement of poorly water-soluble drugs. J. Pharm. 2003;254:137–45.

    CAS  Article  PubMed  Google Scholar 

  11. Babu MM, Prasad GV, Chaudhry DS, Ramana MKV. Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine. Int J Pharm. 2002;234:1–17.

    Article  Google Scholar 

  12. Mutalik S, Anju P, Manoja K, Ushaa AN. Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach. Int J Pharm. 2007;3:218–26.

    Google Scholar 

  13. Coates JP. A practical approach to the interpretation of infrared spectra. In: Meyers RA, editor. Encyclopedia of analytical chemistry. Chichester: Wiley; 2000. p. 10815–37.

    Google Scholar 

  14. Saathoff N, Lode H, Neider K, Depperman KM, Borner K. Koeppe P. Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an H2 receptor antagonist. Antimicrob Agents Chemother. 1992;36:796–800.

    CAS  PubMed  Google Scholar 

  15. Manciet SC, Brossard D, Decroix MO, Robert F, Chaumeil JC. Cefpodoxime proxetil protection from intestinal lumen hydrolysis by oil-in-water submicron emulsions. Int J Pharm. 1998;165:97–106.

    Article  Google Scholar 

  16. Taha E, Ghorab D, Zaghloul AA. Bioavailability assessment of vitamin A self-nanoemulsified drug delivery system in rats: a comparative study. Med Princ Pract. 2007;16:355–9.

    Article  PubMed  Google Scholar 

  17. Manciet SC, Brossard D, Decroix MO, Robert F, Chaumeil JC. Cefpodoxime-proxetil protection from intestinal lumen hydrolysis by oil-in-water submicron emulsions. Int J Pharm. 1997;157:153–61.

    Article  Google Scholar 

  18. Borin MT, Driver MR, Forbes KK. The effect of food on absorption of cefpodoxime proxetil tablets. Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington: American Society for Microbiology; 1992. p. 971, 272.

  19. Klaus SK, Hofheinz W, Laneury JP, Duchene P, Shedlofsky S. Blouinr A. Stability of cephalosporin prodrug esters in human intestinal juice: implications for oral bioavailability. Antimicrob Agents Chemother. 1998;42(10):2602–6.

    Google Scholar 

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Acknowledgements

The authors would like to acknowledge Birbal Sahni Institute of Palaeobotany, Lucknow (India) for providing SEM facility. The authors also would like to acknowledge Radha Raman College of Pharmacy, Bhopal (India) for providing facilities for in vivo animal study and School of Pharmaceutical Sciences, RGPV, Bhopal (India) for providing all necessary facilities during the research work.

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  1. School of Pharmaceutical Sciences, Rajive Gandhi Technical University, Airport Bypass Road, Gandhi Nagar, Bhopal, Madhya Pradesh, 462036, India

    Fahim Khan, Rajesh Katara & Suman Ramteke

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  1. Fahim Khan
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  2. Rajesh Katara
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  3. Suman Ramteke
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Correspondence to Suman Ramteke.

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Khan, F., Katara, R. & Ramteke, S. Enhancement of Bioavailability of Cefpodoxime Proxetil Using Different Polymeric Microparticles. AAPS PharmSciTech 11, 1368–1375 (2010). https://doi.org/10.1208/s12249-010-9505-x

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KEY WORDS

  • cefpodoxime proxetil
  • chitosan
  • methylcellulose
  • microparticles
  • sodium alginate