Assessing The Rationale Of Fdc Containing Ofloxacin And Azoles: Dissolution, Permeation And Antimicrobial Studies

ABSTRACT

Objective: To study fixed-dose combinations (FDC) of antibacterial and antiprotozoal products (ofloxacin and azoles), prescribed for the treatment of diarrhea. Methods: Rationality of these FDC products was verified by assessing parameters such as drug content and release by assay and dissolution tests, respectively mentioned in the Indian Pharmacopoeia (IP). Amount of drug solubilized and permeated as per the Biopharmaceutics Classification System (BCS) was determined. Ex vivo permeation study was performed on the gut of goat using the everted gut sac technique. Antimicrobial efficacy in terms of minimum inhibitory concentration (MIC) was assessed using agar well diffusion method against Shigella boydii, the causative agent for diarrhea. Comparative studies were performed on an individual as well as combination doses of antibacterial and antiprotozoal products for the synergistic effects to assess the rationale of these FDC. Results: The BCS solubility of ciprofloxacin (CPX), norfloxacin (NFX) and tinidazole (TNZ) was high in acidic medium (pH 1-5) and decreased at pH above 5. The assay studies showed that the individual drug contents of FDC were within the IP limits. In vitro dissolution results for both, individual drugs and their combination illustrated 99 % drug release within 30 min in 0.01N HCl. Ex vivo permeation of TNZ was higher than CPX and NFX in individual drugs. No significant change in the permeation rate was observed for individual drugs and their FDC. CPX and NFX exhibited more antimicrobial activity in terms of inhibitory zones than their FDC with antiprotozoal TNZ, above 2.5 µg/ml MIC. The pharmaceutical, biopharmaceutical and antimicrobial evaluation study showed the similarity of FDC with the individual drugs. Conclusion: The study showed no significant data to justify the therapeutic advantage of FDC over individual drugs.