RESEARCH PAPER Development of New Localized Drug Delivery System Based on Ceftriaxone-Sulbactam Composite Drug Impregnated Porous Hydroxyapatite: A Systematic Approach for In Vitro and In Vivo Animal Trial Biswanath Kundu & Chidambaram Soundrapandian & Samit K. Nandi & Prasenjit Mukherjee & Nandadulal Dandapat & Subhasis Roy & Bakul K. Datta & Tapan K. Mandal & Debabrata Basu & Rupnarayan N. Bhattacharya Received: 1 February 2010 / Accepted: 22 April 2010 / Published online: 13 May 2010 # Springer Science+Business Media, LLC 2010 ABSTRACT Purpose Present investigation deals with an extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis, using hydroxyapatite porous scaffolds. Materials and Methods Hydroxyapatite was synthesized in the laboratory by wet chemical method, different porous scaffolds have been fabricated. In vitro studies include variation of porosity with interconnectivity, pore-drug interfacial studies by SEM-EDAX and drug elution studies (by HPLC) both in contact with PBS and SBF at ~37°C. In vivo trials were based on experimental osteomyelitis in rabbit model induced in tibia by Staphylococcus aureus. Characterizations included observa- tion of histopathology, radiology and estimation of drug in both bone and serum for 42 days by HPLC method and subsequent bone-biomaterial interface by SEM. Results It was established that lower pore percentage with a distribution of mainly micro-pores were found to be superior over the higher pore percentage both in vitro and in vivo. The criteria was matched with the 50N50H samples which had 50–55% porosity with an average pore size ~110 μm, having higher interconnectivity (10–100 μm), moderately high adsorp- tion efficiency (~50%) when loaded with CFS (drug combina- tions consisting of irreversible b-lactamase inhibitor and b-lactam antibiotic). CFS release from HAp implants were faster in PBS than SBF. Further, both the results of in vitro and in vivo drug elution after 42 days showed release higher than minimum inhibitory concentration of CFS against Staphylococcus aureus. In vivo studies also proved the superiority of CFS loaded HAp implants than parenteral group based on eradication of infection and new bone formation. B. Kundu : C. Soundrapandian : N. Dandapat : D. Basu Bioceramics and Coating Division, Central Glass and Ceramic Research Institute, Kolkata, India B. Kundu e-mail: biswa_kundu@rediffmail.com C. Soundrapandian e-mail: soundr@rediffmail.com N. Dandapat e-mail: nanda_dandapat@yahoo.co.in D. Basu e-mail: dbasu@cgcri.res.in S. K. Nandi (*) : P. Mukherjee : S. Roy Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata, India e-mail: samitnandi1967@gmail.com P. Mukherjee e-mail: vetprasenjit@gmail.com S. Roy e-mail: subhasisvet@yahoo.co.in B. K. Datta : T. K. Mandal Department of Veterinary Pharmacology and Toxicology, West Bengal University of Animal and Fishery Sciences, Kolkata, India B. K. Datta e-mail: drbkd75@gmail.com T. K. Mandal e-mail: drtkm48@yahoo.co.in R. N. Bhattacharya Department of Plastic Surgery, R.G. Kar Medical College and Hospital, Kolkata, India e-mail: rupnarayan.bhattacharya@gmail.com Pharm Res (2010) 27:1659–1676 DOI 10.1007/s11095-010-0166-y