Development and Optimization of a Floating Multiparticulate Drug Delivery System for Norfloxacin.

OBJECTIVES: Norfloxacin is a synthetic broad-spectrum antibacterial drug having poor bioavailability and pH-dependent solubility. The purpose of the present study was to develop a gastroretentive floating multiparticulate drug delivery system for norfloxacin.
MATERIALS AND METHODS: Norfloxacin core pellets were prepared using microcrystalline cellulose (MCC) and polyvinylpyrrolidone K30 (PVP K30) by extrusion and spheronization. A 3-level, 3-factor, 17-run experimental Box-Behnken design was adopted to optimize levels of variables in the pellets' formulations. The selected independent variables were amounts of MCC and PVP K30 and spheronizing speed and the dependent variables were aspect ratio and hardness of pellets. Sodium bicarbonate and hydroxypropyl methylcellulose K15M in the ratios of 1:1, 1:2, and 2:1 (w/w) on a dry solid basis were incorporated into the norfloxacin pellets and they were further coated with Eudragit RL 100 using a fluidized bed processor to obtain weight gain of 5%, 10%, and 15% w/w. The fourier transform infrared spectrum, scanning electron microscopy, physical characterization, particle size distribution analysis, floating studies, and in vitro drug release studies of the pellets were evaluated.
RESULTS: Among the floating multiparticulate pellets batches, batch B-22 was found to be optimized based on the criteria of attaining the minimum floating lag time (<10 min) and the maximum value of drug released 82.11% in 8 h. The percentage drug release for batches B-21 and B-23 was 91.12% in 5 h and 60.67% in 8 h, respectively. The drug release studies indicated that as the Eudragit RL 100 polymer coat increases the drug release decreases, producing sustained release of norfloxacin. The floating studies revealed that 70%-90% of pellets remained floating for up to 8 h. All the batches have excellent flow properties with angle of repose in the range of 25.5±0.49° to 28.02±0.30°, and Carr's index and Hausner's ratio in the range of 5% to 15% and 1.05±0.3 to 1.14±0.3, respectively.
CONCLUSION: The significant outcome obtained in the study is that such an approach can be effectively employed for improvement of the bioavailability of drugs having poor absorption in the lower part of the gastrointestinal tract with enhanced therapeutic efficacy. ©Copyright 2019 Turk J Pharm Sci, Published by Galenos Publishing House.