Formulation and Comparative Characterization of Methylcellulose, Carbomer and Petrolatum Gels for Topical and Transdermal Delivery of Zosyn (Piperacillin/Tazobactam) Antibiotics

Abstract

Piperacillin/Tazobactam otherwise known as Zosyn is a broad-spectrum combination antibiotic used to treat severe infections. It combines the high antibiotic activity of piperacillin with β-lactamase inhibitor properties of tazobactam that helps to restore the susceptibility of bacteria to the antibiotic and prevents resistance. Despite this interesting pharmacological profile, Zosyn is given intravenously because of its poor oral absorption and short half-life of between only 0.8 and 1.1 hours. However, this system of delivery is not convenient because it is invasive, requires continuous monitoring of patients, and incompatibility issues with other intravenous therapy. The purpose of this study, therefore, was to comparatively characterize an extended release gel formulation from Methylcellulose, Carbomer and Petrolatum and evaluate their suitability for topical and transdermal administration of the drug.Methodology: Gels with 1%, 5% and 10% drug loadings were prepared with the three polymers. The physical characterization of the formulations was done for: drug release using dissolution apparatus; percutaneous absorption in rat skin using microporation technique and Franz cell apparatus. Drug stability studies were conducted at 25°C, 37°C and 45°C and at skin pH of 5. The formulations were also tested for chemical degradation under acidic/ basic and oxidizing/reduction conditions similar to those found on the skin and in wounds with 0.01mol/l HCL, 0.01 mol/l NaOH, 0.1% H 2 O 2 , and 1M KI for 2 hours. Results:The results showed that the gel with 10% drug loaded Methylcellulose formulation was more stable at temperatures studied and less susceptible to chemical degradation for all the chemicals used. The release of drug from the formulations was relatively high in the Methylcellulose (40.9%) and Carbomer (27.59%) gels but were limited in the Petrolatum (3.97%). Furthermore, transdermal delivery using microporation showed high permeation of 12.7%, 6.08% and 6.97% for the 10% drug loaded gels of Methylcellulose, Carbomer and Petrolatum respectively. The drug in the Methylcellulose was found to be subjected to higher degradation in basic medium by an oxidation pathway. Conclusion:The 5% methylcellulose gel formulation containing 10% Zosyn loading was found to have the most potential for effective topical administration and extended-release transdermal delivery of the Zosyn.