Experimental and molecular modeling approach to optimize suitable polymers for fabrication of stable fluticasone nanoparticles with enhanced dissolution and antimicrobial activity.

BACKGROUND AND AIM: The challenges with current antimicrobial drug therapy and resistance remain a significant global health threat. Nanodrug delivery systems are playing a crucial role in overcoming these challenges and open new avenues for effective antimicrobial therapy. While fluticasone (FLU), a poorly water-soluble corticosteroid, has been reported to have potential antimicrobial activity, approaches to optimize its dissolution profile and antimicrobial activity are lacking in the literature. This study aimed to combine an experimental study with molecular modeling to design stable FLU nanopolymeric particles with enhanced dissolution rates and antimicrobial activity. METHODS: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles. RESULTS AND CONCLUSION: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C-8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P<0.05) compared to the unprocessed counterpart. The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against gram-positive bacteria compared to the unprocessed FLU and positive control.

ASSESSMENT OF GUAR AND XANTHAN GUM BASED FLOATING DRUG DELIVERY SYSTEM CONTAINING MEFENAMIC ACID.

We aimed to assess guar and xantban gum based floating drug delivery system containing mefenamic acid. Floating tablets of nefenamic acid were formulated with different concentrations of guar and xanthan gum via wet granulation method. The flow properties of granules that is: bulk density, tapped density, flow rate, Carr index, Hausner's ratio, compressibility index and angle of repose as well as physical parameters of the compressed tablets including: hardness, friability, thickness and swelling indices were determined and found to be good. Xanthan gum was superior to guar gum in maintaining drug release, but a combination of polymers was found to be the best for achieving sustained release up to 12 h due to the synergistic effect of both gums. Drug release mechanism was best explained by Korsmeyer-Peppas model. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies showed absence of any visible interaction. Stability studies at 40°C (75% RH) showed that the formulation was stable at elevated temperature. It can be concluded that floating tablets can be used as a sustained release matrix due to their superior characteristics.

Naproxen release from sustained release matrix system and effect of cellulose derivatives.

The present study was conducted to investigate the low viscosity grades of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix tablets. Both HPMC and EC were incorporated in the matrix system separately or in combinations by wet granulation technique. In vitro dissolution studies indicated that EC significantly reduced the rate of drug release compared to HPMC in 12 hour testing time. But, no significant difference was observed in the release profiles of matrix tablets made by higher percentages of EC. The tablets prepared with various combinations of HPMC and EC also failed to produce produce the desired release profiles. However, comparatively linear and desirable sustained release was obtained from EC-based matrix tablets prepared by slightly modifying the granulation method. Moreover, two different compression forces used in tableting had no remarkable effect on the release profile of naproxen.