Preparation and Evaluation of Chitosan and PLGA Based Implants for the Delivery of Cefotaxime

Abstract

The poor bioavailability of cefotaxime and limitation of conventional system limits the delivery of antibacterial drug cefotaxime for bone infection treatment. In the current study in situ chitosan implant containing cefotaxime was developed. Injectable implantable drug delivery system containing Cefotaxime was prepared by physically mixing β-glycerophosphate with chitosan in different concentrations. The objective of this study was to standardize the concentrations of the ingredients so as to develop formulation that remains liquid when stored at 4ºC but forms a gel, in minimum time, when injected or when its temperature is raised to 37oC. Injectable in-situ implant before injection was clear and transparent. Gelation temperature significantly increase from 32.6°C ±0.1 to 48.43°C ±0.1 of all formulation. Percentage drug content of all formulation were found in the range of 82.42±1.93 to 99.43±0.55. The syringeability of the final solutions greatly decreased with the increase of chitosan concentration. The release pattern for all formulations was biphasic, comprising an initial burst effect followed by an almost sustained continuous phase. After an initial burst release, the drug entrapped into the chitosan/Gp gel was released slowly. Local delivery of chemotherapeutic agent by controlled- release polymers is a new strategy with the potential to maximize the antibacterial effect of a drug to treat bone infection. The system formulated with cefotaxime was found to be stable and the release profiles of a formulation with chitosan and beta-GP showed almost Higuchi equation release kinetics. The drug release of chitosan imlant containing cefotaxime was found to be more as compare to PLGA implant.

  • Page Number : 203-216
  • Keywords
    Cefotaxime, Chitosan, PLGA
  • DOI Number
    https://doi.org/10.15415/jptrm.2014.22014
  • Authors
    • Pankaj GahiyeAkal College of Pharmacy and Technical Education, Mastuana Sahib, Sangrur, Punjab, India
    • Sanjay BajajSelect Bioscience Pvt. Ltd. Chandigarh, India

References

  • Chen R.H., Tsaih M.L., & Lin W.C. (1996.) Effects of chain flexibility of chitosan molecules on the preparation, physical, and release characteristics of the prepared capsule. Carbohydrate Polymer, 31,141-148. http://dx.doi.org/10.1016/S0144-8617(96)00047-1
  • Cho J., Heuzey M.C., Begin A., & Carreau P.J. (2005). Physical gelation of chitosan in the Presence of β-glycerophosphate: The effect of temperature. Biomacromolecules, 6, 3267-3275. http://dx.doi.org/10.1021/bm050313s
  • Christenson, E.M. (2006). Nanobiomaterial Applications in Orthopedics. Wiley InterScience.
  • Eiff, C.V. (2005). Infections Associated with Medical Devices Pathogenesis, Management and Prophylaxis, Adis Data Information BV 65 (2), 179-214.
  • Hannallah D., Peterson B., Lieberman JR., Fu F.H., Huard J (2002). Gene therapy in orthopedic surgery. J Bone Joint Surg. Am., 84(6), 1046-1061.
  • Kempe S., Metz H., Bastrop M., Hvilsom A., Contri R.V., & Mäder K. (2008). Characterization of thermosensitive chitosan-based hydrogels by rheology and electron paramagnetic resonance spectroscopy. European J. Pharm. Biopharm., 68,26–33. http://dx.doi.org/10.1016/j.ejpb.2007.05.020
  • Lazzarini, L. (2005). Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials?.International Journal of Infectious Diseases 9, 127-138.http://dx.doi.org/10.1016/j.ijid.2004.09.009
  • Limin W., Jan P.S. (2010). Thermogelling chitosan and collagen composite hydrogels initiated with b-glycerophosphate for bone tissue engineering. Biomaterials, 31, 3976-3985. http://dx.doi.org/10.1016/j.biomaterials.2010.01.131
  • Mirzaee M., Owlia P. (2009). Comparison of the bactericidal activity of amikacin in free and liposomal formulation against gram-negative and gram-positive bacteria. Jundishapur Journal of Natural Pharmaceutical Products, 4(1), 1-7.
  • Ramteke K.H., Dhole S.N. & Patil S.V. (2012). Transdermal Drug Delivery System: A Review. Journal of Advanced Scientific Research, 3(1), 22-35.
  • Ta H.T., Dass C.R., & Dunstan D.E. (2008). Injectable chitosan hydrogels for localised cancer therapy. Journal of Controlled Release, 126,205-216. http://dx.doi.org/10.1016/j.jconrel.2007.11.018
  • “WHO Model List of Essential Medicines”. World Health Organization. October 2013. Retrieved 22 April 2014.
  • Wu, P., Grainger, D. (2006). Drug /device combinations for local drug therapies and infection prophylaxis. Biomaterials 27, 2450-2467. http://dx.doi.org/10.1016/j.biomaterials.2005.11.031
  • Van de Belt H., Neut D., Schenk W., van Horn JR., van der Mei HC., Busscher HJ (2001). Infection of orthopedic implant and the use of antibiotic loaded bone cements, Acta Orthop. Scand., 72(6), 557-571. http://dx.doi.org/10.1080/000164701317268978
  • Zhi-peng C., Wen L., Dan L., Yan-yu X., Hong-xuan C., Jun C., & Weidong L. (2012). Development of brucine-loaded microsphere/thermally responsive hydrogel combination system for intra-articular administration. Journal of Controlled Release, 162, 628-635. http://dx.doi.org/10.1016/j.jconrel.2012.07.037
  • Zhou H.Y., Zhang Y.P., Zhang W.F., & Chen X.G. (2011). Biocompatibility and characteristics of injectable chitosan-based thermo sensitive hydrogel for drug delivery. Carbohydrate Polymer, 83(4), 1643–1651. http://dx.doi.org/10.1016/j.carbpol.2010.10.022

  • Published Date : 2014-11-30