Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (−18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.

The poly(D,L-lactide-co-glycolide) (PLGA) based second-generation nanocrystals prepared by modified nanoprecipitation method, is the method of choice for encapsulation of both lipophilic and hydrophilic drugs. In this study, nanoprecipitation technique was adopted to develop second generation nanocrystals of PLGA loaded with metformin HCl (MHc). Poloxamer 188 with three different concentrations (0.5, 0.75, 1% w/v) in combination with PLGA at 1, 2, 3% concentrations (w/v) successfully produced MHc loaded PLGA second generation nanocrystals. The effects of poloxamer 188, amphiphilic triblock copolymer on carrier particle size, surface morphology, polydispersity index, zeta potential, drug entrapment efficiency and drug release of nanoformulation were investigated. The optimized formulation of second-generation nanocrystals with concentrations 0.75% w/v poloxamer 188 and 2% w/v PLGA, could produce particle size of 114.6 nm, entrapment efficiency of 63.48% and drug release 80.23% at 12 h. A blank formulation with the same composition as optimized formulation without addition of poloxamer188 compared with optimized formulation, exhibited nanoparticles of larger mean particle size of 212.9 nm with entrapment efficiency of 68.47% and 50.5% drug release at 12 h. Transmission electron microscopy (TEM) analysis of the nanoformulations revealed that poloxamer188 greatly contributed to smooth, spherical morphology of nanosize polymeric nanoparticles. Further Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on nanoformulation emphasized the significance of poloxamer188 in formulation and development of optimized MHc loaded PLGA nanosuspensions of second generation nanocrystals. In conclusion, the study emphasizes that poloxamer 188 was a versatile excipient, which played a pivotal role in producing nanosize carrier with high drug release profile of MHc loaded PLGA nanosuspensions of second generation nanocrystals.