Introduction: Second generation functionalized nanocrystal is the advancement of nanocrystal technology with great potential to accommodate BCS (Biopharmaceutical Classification System) class II drugs to meet their formulation and drug delivery challenges. Gliclazide is a BCS class II drug used in the treatment of type 2 diabetes, shows poor water solubility and low rate of dissolution, leads to poor and variable oral bioavailability. The second generation poly(D,L-lactide-co-glycolide) (PLGA) Hydroxypropyl methylcellulose (HPMC) based functionalized nanocrystals of gliclazide were prepared by a combination method of emulsion diffusion-high pressure homogenization-solvent evaporation. Methods: Gliclazide second generation nanocrystals were fabricated with taguchi orthogonal experimental design in combination of step up and top down nanoformulation strategies using drug-polymer (PLGA) ratio at 1:0.5, 1:0.75, 1:1 with HPMC(0.5, 0.75, 1% w/v) as stabilizer. The formulated gliclazide PLGA-HPMC nanocrystals were investigated on particle size, polydispersity index, zeta potential, solubility study, drug entrapment efficiency, in vitro drug release, and surface morphology and compatibility studies. The gliclazide PLGA nanocrystals formulation was prepared with Drug : PLGA at 1: 1 ratio with concentrations 0.75% w/v HPMC at 5 homogenization cycles with 1000bar produce optimized gliclazide nanocrystals. Results: The optimized MSGNC8 formulation
showed particle size of 239.9 nm, entrapment efficiency 98.62%, and drug release of 43.75%, 82.12% and 98.08% at 3hrs, 24hrs, and 48hrs compared to pure gliclazide % drug release of 28.73%, 67.51% and 78.41% at 3hrs, 24hrs, 48hrs respectively. The solubility study of optimized formulation shows eight folds increased in saturation solubility compared to pure drug. Scanning electron microscopy (SEM) analysis of the gliclazide nanocrystals revealed that
gliclazide retained its crystal morphology in polymeric nanocrystals. Further, fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies on gliclazide PLGA-HPMC nanocrystals emphasize drug and excipient compatibility in development of gliclazide nanocrystals. Conclusion: The potential outcomes of research findings emphasize that the developed gliclazide second-generation nanocrystals, which resulted in increase in drug solubility and rate of dissolution with delayed modified release, can be explored in delivery of gliclazide for type 2 diabetes management.
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.
Phosphoric acid impregnated activated carbon from date pits (DPAC) was prepared through single step activation. Prepared DPAC was studied for its structural, elemental, chemical, surface and crystal nature. Adsorption ability of the DPAC was assessed through divalent lead ions separation studies. Effect of adsorbent dosage, contact time, pH, operating temperature and initial feed concentration on lead removal by DPAC was studied. Maximum Pb(II) adsorption capacity of 101.35 mg/g was attained for a contact time of 30 min and pH of 6 at 30°C. Increase in initial feed concentration enhanced the adsorption ability of DPAC and the rise in adsorbent dosage resulted in improved Pb(II) removal efficiency. Thermodynamic studies revealed that the lead adsorption on DPAC was exothermic and instantaneous in nature. Kinetic and equilibrium studies confirmed the suitability of pseudo-second order and Langmuir isotherm for divalent lead ions binding on DPAC. Reusability studies showed that HCl was the effective regeneration medium and the DPAC could be reused for a maximum of 4 times with slight reduction in Pb(II) removal efficiency (<10%). Results indicated the promising use of date pits biomass as a low cost and efficient starting material to prepare activated carbon for divalent lead ions removal.
Liquid biphasic flotation (LBF), an integrated process of liquid biphasic system (LBS) and adsorptive bubbles flotation, was used for the purification of C-phycocyanin from S. platensis microalgae. Various experimental parameters such as type of phase forming polymer and salt, concentration of phase forming components, system pH, volume ratio, air flotation time and crude extract concentration were evaluated to maximise the C-phycocyanin recovery yield and purity. The optimal conditions for the LBF system achieving C-phycocyanin purification fold of 3.49 compared to 2.43 from the initial LBF conditions was in polyethylene glycol (PEG) 4000 and potassium phosphate combination, with 250 g/L of polymer and salt concentration each, volume ratio of 1:0.85, system pH of 7.0, air flotation duration of 7 min and phycocyanin crude extract concentration of 0.625 %w/w. The LBF has effectively enhanced the purification of C-phycocyanin in a cost effective and simple processing.
Polyhydroxyalkanoates (PHAs), a family of biodegradable and renewable biopolymers show a huge potential as an alternative to conventional plastics. Extractive bioconversion (in situ product recovery) is a technique that integrates upstream fermentation and downstream purification. In this study, extractive bioconversion of PHAs from Cupriavidus necator H16 was performed via a thermo-separating aqueous two-phase system to reduce the cost and environmental impacts of PHAs production. Key operating parameters, such as polymer concentration, temperature, and pH, were optimized. The strategy achieved a yield and PF of 97.6% and 1.36-fold, respectively at 5% EOPO 3900 concentration, 30 °C fermentation temperature and pH 6. The PHAs production process was also successfully scaled up in a 2 L bioreactor. To the best of our knowledge, this is the first report on extractive fermentation of PHAs from Cupriavidus necator utilizing a thermo-separation system to achieve a better productivity and purity of the target product.