European Journal of Biomedical and Pharmaceutical Sciences

FABRICATION AND CHARACTERIZATION OF LEVOFLOXACIN LUNGS TARGETED DRUG DELIVERY BY THE WAY OF MICROSPHERES

Burhan Ali*, Mohibur Rahman, Nargis Sultana, Dr. Bapan Sarkar and Abdul Muktadir

ABSTRACT

Objective: Pulmonary drug delivery systems offer many advantages over other conventional drug delivery system such as avoidance of first pass metabolism, large surface area suitable for drug absorption and quicker onset of pharmacological activity. One of the drug, Levofloxacin, if formulated into microspheres, could be trapped by filtration in the capillary bed of the lungs. The biodegradable and biocompatible polymer BSA was selected as matrix forming agent. Method: Biodegradable microspheres of levofloxacin has been prepared by emulsification heat stabilization technique using BSA as polymer and characterized by drug loading, size distribution, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), percentage entrapment efficiency, and in vitro release studies. The pharmacokinetics and targeting efficiency of microspheres was studied in vivo in albino rats. Result and Discussion: The microspheres showed drug loading (encapsulation) in the range of 11.00 to 21.10 % with an average size range of 12.33–18.73 μm, depending upon the drug–polymer ratio and emulsifier concentration. They were spherical in nature and free from surface drug as evidenced by the SEM photographs. FT-IR and DSC studies revealed the absence of drug–polymer interaction. In vitro drug release studies showed a biphasic release pattern for all formulations with an initial burst effect followed by slow release for almost 24 hours. The in vitro release profile of the microspheres matched the Korsmeyer’s Peppas release pattern. Formulation F7 with good drug content and particle size less than 15 μm was selected for in vivo pharmacokinetic and drug targeting studies in comparison with conventional levofloxacin injection. The in vivo pharmacokinetic evaluation on albino rats demonstrated increased bioavailability with microsphere formulation in comparison to the traditional solution form. The significant increase in bioavailability shall enable one to reduce the frequency of levofloxacin administration and would effectively reduce the dose related side effects. The average targeting efficiency of drug loaded microspheres was found to be 53.23% of the injected dose in lungs, 37.96% in liver and 4.63% in spleen after 12 hours, whereas the concentration of drug from levofloxacin injection was 38.52% in lungs, 46.35% in liver, and 4.12% in spleen. These results revealed that the drug loaded microspheres showed preferential drug targeting to lungs followed by liver and spleen. Stability studies revealed that at 40±2ºC microspheres are stable after 90 days. Histopathological studies proved that the tissue compatibility of levofloxacin microspheres is safe. Conclusion: From the experimental data obtained from injectable microsphere was found to be an efficient tool in encapsulating levofloxacin with an excellent controlled release profile. This formulation could be an effective tool in targeting to lungs and helps in treating pneumonia.

Keywords: Levofloxacin, Bovine serum albumin, injectable microspheres, pneumonia.