Dizaj i statistička optimizacija liposfera s glipizidom pomoću metodologije odgovora površine

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 ± 1.38 µm, 86.28 ± 1.32 %, 77.23 ± 2.78 % and 5.60 ± 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.32 faktorijalni dizajn primijenjen je za pripravu liposfera s glipizidom metodom separacije pomoću emulzija koristeći parafinski vosak i starinsku kiselinu kao tvari za usporavanje. Pomoću F-testa praćen je učinak kritičnih varijabli tijekom formuliranja, tj. količina parafinskog voska (X1) i udio stearinske kiseline (X2) na srednji promjer liposfera (dg), postotak inkapsulirane ljekovite tvari (% EE), oslobađanje ljekovite tvari nakon 12 h (rel12) te vrijeme potrebno za oslobađanje 50% ljekovite tvari (t50). Pomoću multiple linearne regresijske analize (MLRA) i analize varijabli (ANOVA) za svaki su parametar načinjeni matematički modeli koji sadrže samo značajne varijable. Proučavanje varijabli na oba načina ukazalo je na njihov značajan utjecaj (p < 0,05) na parametre liposfera. Postavljanjem ograničenja na zavisne i nezavisne varijable provedena je numerička optimizacija na principu poželjnosti. Eksperimentalne vrijednosti dg, % EE, rel12 i t50 optimiziranih formulacija bile su 57,54 ± 1,38 µm, 86,28 ± 1,32%, 77,23 ± 2,78% i 5,60 ± 0,32 h. Dobivene eksperimentalne vrijednosti iznosile su vrlo slične vrijednostima predviđenim matematičkim modelima. Oslobađanje glipizida iz liposfera slijedio je kinetiku prvog reda i okarakterizirano je Higuchijevim difuzijskim modelom. Optimizirane liposfere su nakon peroralne primjene na štakorima pokazale produljeni antidijabetički učinak

Enhancement of the Neuroprotective Effect of Curcumin in Combination with Piperine in Nicotinamide-Streptozotocin Induced Diabetic Rats.

Introduction: Curcumin (CUR) is a hydrophobic molecule with poor bioavailability.Piperine is reported to enhance the bioavailability of drugs by increasing absorption in the small intestine and decreasing glucuronidation in the liver.Objective:The objective of the present investigation was to evaluate the neuroprotectiveeffect of curcuminincombinationwith piperine innicotinamide- streptozotocin (NIC-STZ) induced diabetic rats.Methods:MaleWistar rats were divided into groups viz.vehicle control, disease control,glibenclamide (1), glibenclamide+ piperine(1+50), curcumin (50) and curcumin (50) with piperine10, 30 and 50.All the groups except vehicle control were induced diabetes by injecting NIC-STz. The animals received treatment daily for six weeks after the confirmation of diabetic status.Behavioural, biochemical and histological parameters were evaluated to access the neuroprotective effect.Results: Oral administration of curcumin + piperine (50+50 mg/kg) caused a significant fall in blood glucose level. Disease control showed increased paw withdrawal latency and nociceptive threshold compared with vehicle control. Curcumin + piperine treated animals showed decreased paw withdrawal latency. Combination of curcumin + piperine (50+50 mg/kg, p.o.) showed significant antioxidant property by increasing tissue GSH and SOD and lowering lipid content (MDA) compared to the disease control group. The histopathological study showed reduced damage to the sciatic nerve in curcumin + piperine (50+50 mg/kg, p.o.) treated group.Conclusion: Itis concluded that the curcumin-piperine combination reducedthe degeneration of sciatic nerve by reduction of lipid peroxidation and lowering oxidative stress indicating the neuroprotective effect in diabetic neuropathy