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.
Methods: The effects of independent variables (poloxamer 407 and hydroxypropyl methyl cellulose (HPMC) concentration) on various dependent variables (gelling capacity, pH and viscosity) were investigated by using 32 factorial design and organoleptic evaluation was done with descriptive analysis.
Results: The optimized formula of chloramphenicol in situ gel yielded 9 variations of poloxamer 407 and HPMC bases composition in % w/v as follows, F1 (5; 0.45), F2 (7.5; 0.45), F3 (10; 0.45), F4 (5; 0.725), F5 (7.5; 0.725), F6 (10; 0.725), F7 (5; 1), F8 (7.5; 1), F9 (10; 1). The results indicated that the organoleptic, pH, and gelling capacity parameters matched all formulas (F1-F9), however, the viscosity parameter only matched F3, F6, F8, and F9. Based on factorial design, F6 had the best formula with desirability value of 0.54, but the design recommended that formula with the composition bases of poloxamer 407 and HPMC at the ratio of 8.16 % w/v and 0.77 % w/v, respectively, was the optimum formula with a desirability value of 0.69.
Conclusion: All formulas have met the Indonesian pharmacopoeia requirements based on the physical evaluation, especially formula 6 (F6), which was supported by the result of factorial design analysis.