Formulation-Development and Evaluation of Polysorbate-Phospholipid Mixed Micelles of Piperine Loaded with Azithromycin

Abstract

The overall goal of this paper was to develop polysorbate-phospholipid micelles of piperine loaded with azithromycin, and to study the effect and mechanisms enhancing the oral bioavailability of piperine and also to inhibit the bacterial growth. For the preparation of polysorbate-phospholipid-piperine mixed micelles loaded with a drug, polysorbate and phospholipid were optimized. Polysorbate concentration at 5.5% w/v showed the maximum solubility of piperine which was just similar to 5.0% w/v CMC value so, from such studies, it was confirmed that optimum concentration of polysorbate 80 required for maximum solubilization of piperine was 5.5% w/v. The maximum CMC of polysorbate 80 and phospholipid was found in batch F3 i.e. 62.4414 and 83.1122, respectively. Based on the optimization of phospholipid and polysorbate 80, three final batches were selected as the best batch i.e. F2, F3, and F4 (1:10:4, 1:15:4 and 1:20:4, respectively) for final formulation. In the formulation, maximum solubility was found in batch F3 i.e. 11.3057 mg/ml. The size of the nanoformulations was found to be 0.3396 r.nm by using zeta analyzer. The drug release was determined in 0.1 N HCl at 5, 10, 15, 30 and 60 min. Further, 7.4 pH phosphate was added and release was determined at 30, 60, 120, 180 and 240 min. It was noted that formulation F3 has maximum drug content and F1 was found as maximum entrapment efficiency. The maximum drug release was found in the formulation F3. The approach of using phospholipid nanoformulations loaded with azithromycin showed antibacterial activity in the nutrient agar plate. These formulations prevent the visual growth of bacteria. It was shown that the maximum zone of inhibition was found at the concentration of 100mg/ml. The MIC endpoint at the lowest concentration of formulation at which there is minimum visual growth around the dice was found to be 50 mg/ml.