Nano-crystallization of flubendazole for enhanced dissolution rate and improved in vivo efficacy against Trichinella spiralis.

The aim was to enhance the dissolution rate and in vivo efficacy of flubendazole against trichinella spiralis. Flubendazole nanocrystals were developed by controlled anti-solvent recrystallization. Saturated flubendazole solution was prepared in DMSO. This was injected into phosphate buffer (pH 7.4) containing Aerosil 200, Poloxamer 407 or sodium lauryl sulphate (SLS) while mixing using paddle mixer. The developed crystals were separated from DMSO/aqueous system by centrifugation. The crystals were characterized using DSC, X-ray diffraction and electron microscopy. The crystals were suspended in Poloxamer 407 solution and dissolution rate was monitored. Optimal formulation was administered to Trichinella spiralis infected mice. Administration protocol attacked the parasite in intestinal, migrating and encysted phases. The crystals were spherical nanosized with formulation employing 0.2% Poloxamer 407 as stabilizer being optimum with size of 743.1 nm. DSC and X-ray supported particle size reduction with partial amorphization. Optimal formulation showed fast dissolution to deliver 83.1% after 5 min. Nanocrystals provided complete eradication of intestinal Trichinella and reduced larval count by 90.27 and 85.76% in migrating and encysted phases compared with marginal effect in case of unprocessed flubendazole. The efficacy was clearer from improved histopathological features of the muscles. The study introduced nano-crystallization for enhanced dissolution and in vivo efficacy of flubendazole.

Effect of water-in-oil microemulsions and lamellar liquid crystalline systems on the precorneal tear film of albino New Zealand rabbits.

The aim of this study is to investigate the effect of phase transition water-in-oil (w/o) microemulsions (ME) and liquid crystalline systems (LC) on the precorneal tear film (PCTF). The study used six albino NZ rabbits and monitored the integrity and stability of the PCTF before and after instillation of test formulations. The effects were evaluated by assessment of the PCTF lipid layer using interferometry, tear evaporation rate measurements, and indirect estimation of tear volume. Ocular application of test formulations changed the appearance of the PCTF lipid layer, indicating lipid layer disruption. The recovery time was longer in case of ME compared with an aqueous solution (SOL). The tear evaporation rate was increased after application of both ME and LC systems compared with the SOL, with the LC system showing the greatest effect. Tear volume measurement results revealed minimal changes associated with the instillation of both ME systems. Whilst phase transition w/o ME systems can interact with the PCTF lipid layer in albino New Zealand rabbits, their effect on the volume of resident tears was found to be minimal.