Optimization and characterization of nimesulide bilayer tablets by response surface methodology

The objectives of this present investigation were to develop and formulate nimesulide bilayer tablets by using different polymer combinations and fillers, to optimize the formulations for different drug release variables by orthogonal design and central composite design-surface methodology and to evaluate drug release pattern of the optimized product. The bilayer tablet containing a fast release layer（FRL） and a sustained release layer（SRL） provided an initial burst release of nimesulide, followed by the sustained release for a period of time. The optimal formulation obtained was as follows：（I） the formulation of FRL： nimesulide, 50 mg; lactose, 92 mg; starch, 22 mg; CCMC-Na, 14 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; magnesium stearate, 0.9 mg; and iron oxide red, 0.1 mg; and（II） the formulation of SRL： nimesulide, 150 mg; HPMC K100LV, 26 mg; HPMC K4M, 33 mg; lactose, 54 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; and magnesium stearate, 0.9 mg. According to the optimal formulation, the biphasic type of release was identified. The in vitro drug dissolution from the bilayer tablets was sustained for about 16 h after releasing 15% of drug in the first 10 min. The developed nimesulide bilayer tablets with improved efficacy can perform therapeutically better than the conventional tablets.

A nanocarrier based on poly(D,L-lactic-co-glycolic acid) for transporting Na^+ and Cl^- to induce apoptosis

Transmembrane anion transporters have attracted significant attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis,in which,most of the synthetic anionic transporters are organic small molecules whose synthesis routes are usually complex and tedious,and the related biological research is also only in infancy.Hence,we synthesized a kind of chloride anion(Cl-)and sodium cation(Na^+)nanocarrier based on poly(D,L-lactic-co-glycolic acid)(PLGA)which was coated with polydopamine(PDA)to provide target release factor.When the nanocarrier arrives in acidic enviro nment such as lysosomes through endocytosis,Cl^-and Na^+will be released fast from the nanocarrier resulting in imbalance of cell homeostasis for inducing apoptosis.Cell experiments show that the nanocarrier promotes apoptosis and leads to an increased concentration of reactive oxygen species.By exploring the concentration of cytochrome c in mitochondria and cytoplasm and the activities of key enzymes caspase-9 and caspase-3 in apoptosis process,it is proved that the apoptotic pathway is caspase-dependent.This novel strategy allows the research of anion transporter no longer limited to artificial synthesis of small molecular and provides a novel and effective direction to investigate ion homeostasis,ion transport and cancer treatment.