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: By adding Hydroxy Propyl Methyl Cellulose (HPMC) as a precipitation inhibitor to conventional SNEDDS, a supersaturable system was prepared. Firstly, the prepared SNEDDS played an important role in increasing the aqueous solubility and hence oral absorption due to nano-range size. Secondly, the S-SNEDDS found to be advantageous over SNEDDS for having a higher drug load and inhibition of dilution precipitation of Dutasteride. Formulated S-SNEDDS (F1-F9) ranged from 37.42 ± 1.02 to 68.92 ± 0.09 nm with PDI 0.219-0.34 and drug loading of over 95 percent.
RESULTS: The study of in-vitro dissolution revealed higher dissolution for S-SNEDDS compared to SNEDDS and Avodart soft gelatin capsule as a commercial product. In addition, higher absorption was observed for S-SNEDDS showing approximately 1.28 and 1.27 fold AUC (0-24h) and Cmax compared to commercial products. Therefore, S-SNEDDS has proven as a novel drug delivery system with a higher drug load, higher self-emulsification efficiency, higher stability, higher dissolution and pronounced absorption.
CONCLUSION: In conclusion, S-SNEDDS could be a newly emerging approach to enhance aqueous solubility in many folds for drugs belonging to BCS Class II and IV and thus absorption and oral bioavailability.