IMPROVEMENT OF BIOAVAILABILITY OF CEFUROXIME AXETIL ORAL SUSPENSION BY INCLUSION COMPLEXATION METHOD
Abstract
Objective: Cefuroxime axetil, a prodrug of Cefuroxime, is a poorly water soluble drug, thus it has got only limited solubility and dissolution rate in gastric fluids. Also, the bioavailability of Cefuroxime axetil oral suspension is only 40-45% when compared to the 60% bioavailability of tablets. The objective of this study was to develop an oral suspension of Cefuroxime axetil with improved oral bioavailability by inclusion complexation method using Hydroxypropyl beta cyclodextrin [HP-Beta-cylcodextrin]
Methods: The complexation of Cefuroxime axetil and HP-Beta cyclodextrin was carried out at 1:1, 1:2, 1:2.5 and 1:3 ratios respectively. The prepared suspensions were evaluated for various parameters like pH, viscosity, re-dispersibility, pourability, and assay and in-vitro dissolution profile. A leading marketed product and the optimized formulation were evaluated for the pharmacokinetic parameters like Cmax, AUC0-t, AUC0-∞ and Tmax in healthy adult male rabbits.
Results: Considering the in-vitro dissolution profile, formulation with 1:2.5 ratios of Cefuroxime axetil and HP-Beta cyclodextrin was selected as the optimized formulation. The Cmax of Optimized formulation and Marketed product were 148±1.26ng/ml and 126±1.52 ng/ml respectively, and the AUC0-t ofOptimized formulation and Marketed product were 989±16.42 ng. h/ml and 613±24.26 ng. h/ml respectively, which shows a significant improvement in the bioavailability of optimized formulation
Conclusion: From the results obtained it can be observed that there is a significant improvement in the bioavailability of optimized formulation compared to the marketed product. This demonstrates that the inclusion complexation method with HP-Beta cyclodextrin can significantly improve the oral bioavailability of Cefuroxime axetil.
Keywords: Cefuroxime axetil, Bioavailability, Beta cyclodextrin, Inclusion complexation
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References
Yuqian Du, Yinglei Zhai, Juhong Zhang, Chunnuan Wu, Cong Luo, Jin Sun, et al. Development and evaluation of taste-masked dry suspension of cefuroxime axetil for enhancement of oral bioavailability. Asian J Pharm Sci 2013;8:287-94.
J Vinod, A Chenthilnathan. Formulation development and evaluation of taste masked Cefuroxime axetil dry suspension, pelagia research library. Der Pharm Sin 2013;4:98-103.
Nieves Ruiz-Balaguer, Amparo Nacher, Vicente G. Casabo, and matilde merino, nonlinear intestinal absorption kinetics of cefuroxime axetil in rats. Antimicrob Agents Chemother 1997;41:445–8.
Khan, Abdul Rehman, Kondawar, Kishan Vishwanth, Gosavi, Arun Shriniwas. Pharmaceutical formulation WIPO Pat. Appl. No. 043707 to Wokhardt Research Centre; 2002.
Nighute AB, Bhise SB. Preparation and evaluation of microcrystals of cefuroxime axetil. Int J PharmTech Res 2009;1:424-30.
A patient information leaflet of Zinnat Suspension, Glaxo Smith Kline Australia Pty Ltd; 2011.
Birhade ST, Bankar VH, Gaikwad PD, Pawar SP. Preparation and evaluation of cyclodextrin-based binary systems for taste masking. Int J Pharm Sci Drug Res 2010;2:199-203.
Ashok R Pateli, Pradeep R Vavia. Preparation and evaluation of taste masked famotidine formulation using drug/β-cyclodextrin/polymer ternary complexation approach. AAPS PharmSciTech 2008;9:544-50.
Arthur H Kibbe. Hand Book of Pharmaceutical Excipients. 3rd edition. American Pharmaceutical Association, USA; 2000. p. 165-8.
J Szejtli, L Szente. Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur J Pharm Biopharm 2005;61:115–25.
Vishnumurthy Vummaneni, Dheeraj Nagpal. Taste masking technologies: an overview and recent updates. Int J Res Pharm Biomed Sci 2012;3:510-24.
Sharma S, Lewis S. Taste masking technologies: a review. Int J Pharm Pharm Sci 2010;2:6-13.
Menjoje AR, Kulkarni MG. A pharmaceutical composition for improving palatability of drugs and process for preparation thereof. U. S Pat. No. 7378109 B2 to Council of Scientific and Industrial Research; 2008.
Soho H, Sultana Y, Khar RK. Tate masking technologies in oral pharmaceuticals. Recent developments and approaches. Drug Dev Industrial Pharm 2004;30:429-48.
Chatap VK. Review on taste masking methods of the bitter drug. Pharmainfo net; 2007. p. 5.
Sarah Gould, Robert C. Scott, 2-Hydroxypropyl-b-cyclodextrin (HP-b-CD): a toxicology review. Food Chem Toxicol 2005;43:451–9.
Michael B James, Leonard G Elliott. A pharmaceutical composition comprising cefuroxime axetil. U. S. Pat. No. 4865851 to Glaxo group ltd; 1989.
Gedam Shweta S, Tapar KK, Borse MD, Ghuge RA. Taste masking and characterization of diphenhydramine hydrochloride by spray drying technique. Int J Pharma Res Dev 2005;1:154-65.